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Polypill in Acute Coronary Syndrome (POLY-ACS)
Acute coronary syndromes (ACS) represent a major contributor to mortality, morbidity, and healthcare costs. Effective therapies are widely available; however, adherence is low. This contributes to worse patient outcomes and increased risk of morbidity and mortality. The once-daily polypill leverages a population-based strategy that has previously demonstrated efficacy in improving adherence and access to therapy in low-resource settings, making it an innovative approach for improving post-ACS care. This study aims to investigate the utility of a polypill-based strategy for patients with ACS with drug eluting stent (DES) placement. The polypill will consist of a high-intensity statin (rosuvastatin 40 mg daily), aspirin 81 mg daily, and prasugrel 10 mg daily.
• Patients admitted with acute coronary syndrome who undergo percutaneous coronary intervention with drug eluting stent placement.
• Age < 18
• Estimated glomerular filtration rate < 30 mL/min/1.73 m2 as measured by the simplified MDRD formula
• Current need for inotropes or with cardiac index < 2.2 L/min/m2
• History of coronary artery bypass graft surgery
• Current need for systemic anticoagulation
• Contraindication to receive any components of the polypill
• History of allergic reaction or intolerance to aspirin, prasugrel, or rosuvastatin
• Comorbidities that might be expected to limit lifespan within the 1-month study period
• Inability to provide written informed consent
Pediatric Influence of Cooling Duration on Efficacy in Cardiac Arrest Patients (P-ICECAP) (ICECAP)
This is a multicenter trial to establish the efficacy of cooling and the optimal duration of induced hypothermia for neuroprotection in pediatric comatose survivors of cardiac arrest. The study team hypothesizes that longer durations of cooling may improve either the proportion of children that attain a good neurobehavioral recovery or may result in better recovery among the proportion already categorized as having a good outcome.
• Age 2 days to < 18 years with corrected gestational age of at least 38 weeks
• Chest compressions for at least 2 minutes
• Coma or encephalopathy after resuscitation from Out-of-Hospital Cardiac Arrest (OHCA)
• Requires continuous mechanical ventilation through endotracheal tube or tracheostomy
• Definitive temperature control device initiated
• Randomization within 6 hours of Return of Spontaneous Circulation (ROSC)
• Informed consent from Legally Authorized Representative (LAR) including intent to maintain life support for 120 hours Exclusion criteria:
• Glasgow Coma Motor Score (GCMS) = 6
• LAR does not speak English or Spanish
• Duration of Cardiopulmonary Resuscitation (CPR) > 60 minutes
• Severe hemodynamic instability with continuous infusion of epinephrine or norepinephrine of 2 micrograms per kilogram per minute (μg/kg/minute) or initiation of Extracorporeal membrane oxygenation (ECMO)
• Pre-existing severe neurodevelopmental deficits with Pediatric Cerebral Performance Category (PCPC) =5 or progressive degenerative encephalopathy
• Pre-existing terminal illness, unlikely to survive to one year
• Cardiac arrest associated with brain, thoracic, or abdominal trauma
• Active and refractory severe bleeding prior to randomization
• Extensive burns or skin lesions incompatible with surface cooling
• Planned early withdrawal of life support before 120 hours
• Sickle cell anemia
• Pre-existing cryoglobulinemia
• Non-fatal drowning in ice covered water
• Central nervous system tumor with ongoing chemotherapy
• Previous enrollment in P-ICECAP trial
• Chronic hypothermia
• New post-cardiac arrest diabetes insipidus
A Randomized, Controlled Trial to Evaluate the Safety and Effectiveness of the Route 92 Medical Reperfusion System (SUMMIT MAX)
The SUMMIT MAX study is a prospective, randomized, controlled, interventional clinical trial to evaluate the safety and effectiveness of the Route 92 Medical MonoPoint® Reperfusion System for aspiration thrombectomy in acute ischemic stroke patients.
• The consent process has been completed and documented according to applicable country regulations and as approved by the IRB / Ethics Committee
• Age >=18 years and <= 85
• Patient presenting with clinical signs consistent with an acute ischemic stroke
• Baseline National Institutes of Health Stroke Scale (NIHSS) score >= 6
• Pre-stroke modified Rankin Score (mRS) <= 1
• Baseline ASPECTS >= 6
• Endovascular treatment initiated (defined as time of first angiogram) within 8 hours from time last known well
• If indicated, thrombolytic therapy shall be initiated per clinical guidelines. If eligible for thrombolytic therapy, subjects should be treated as soon as possible and lytic use should not be delayed regardless of potential eligibility for mechanical neurothrombectomy.
• The patient is indicated for aspiration neurothrombectomy with the Route 92 Medical Reperfusion System as determined by the Investigator
• Angiographic confirmation of a large vessel occlusion of the M1 segment of the middle cerebral artery or distal internal carotid artery
• Known pregnancy or breast feeding
• In the Investigator's opinion, any known comorbidity (including COVID-19 positivity) that may complicate treatment or prevent improvement or follow-up
• Known serious, advanced, or terminal illness with anticipated life expectancy < 12 months
• Known history of severe allergy to contrast medium
• Known to have suffered a stroke in the past 90 days
• Known connective tissue disorder affecting the arteries (e.g. Marfan syndrome, Ehlers-Danlos syndrome)
• Any known previous cerebral hemorrhagic event
• Any known pre-existing coagulation deficiency
• Known hemorrhagic diathesis, coagulation factor deficiency, or oral anticoagulant therapy with INR >3.0
• Known baseline platelet count <50,000/µL
• Known baseline blood glucose of <50 mg/dL or >400 mg/dL
• Known to be participating in another study involving an investigational device or drug
• Clinical symptoms suggestive of bilateral stroke or stroke in multiple territories.
• Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) evidence of recent/ fresh cerebral hemorrhage (the presence of microbleeds is allowed)
• Baseline CT or MRI showing intracranial tumor (except small meningioma <= 2cm) or significant mass effect with midline shift due to the tumor
• Presumed septic thrombus, or suspicion of bacterial endocarditis
• Inability to access the cerebral vasculature in the opinion of the neurointerventional team
• Unlikely to be available for a 90-day follow-up (e.g. no fixed home address)
• Evidence of carotid dissection
• Evidence of cervical carotid artery high-grade stenosis or occlusion (i.e., tandem occlusion)
• Active or recent history of drug abuse (within last 6 months)
• Known history or presence of aneurysm or arteriovenous malformation (AVM) in the territory of the target lesion
• For all patients, severe sustained hypertension with SBP >200 and/or DBP >120; for patients treated with IV tPA, sustained hypertension despite treatment with SBP >185 and/or DBP >110
• Treatment with heparin within 48 hours with a partial thromboplastic time more than two times the laboratory normal
• Renal failure with serum creatinine >3.0 or Glomerular Filtration Rate (GFR) <30
• Ongoing seizure due to stroke
• Evidence of active systemic infection
• Known cancer with metastases
• Cervical carotid stenosis requiring balloon angioplasty or stenting at the time of the procedure
• Angiographic evidence of multiple cerebrovascular occlusions (e.g., bilateral anterior circulation, anterior/posterior circulation)
• Angiographic evidence of known or suspected underlying intracranial vasculopathy or atherosclerotic lesions responsible for the target occlusion
• Angiographic evidence or suspicion of aortic dissection
Efficacy of an m-Health Cardiac Rehabilitation Program in Heart Failure With Preserved Ejection Fraction
Heart failure (HF) portends substantial morbidity, mortality, and health care costs in the United States and the prevalence of heart failure with preserved ejection fraction (HFpEF) relative to HF with reduced ejection fraction (HFrEF) has been increasing. HFpEF is associated with a high morbidity and mortality burden and is projected to be the predominant subtype of HF in the near future. While multiple therapies have proven efficacious for patients with HFrEF, no pharmacological agents have demonstrably been shown to improve outcomes in HFpEF, highlighting the need for novel approaches to HFpEF treatment. Exercise intolerance (EI) is the cardinal symptom of HFpEF, which manifests as dyspnea and fatigue. EI leads to functional deconditioning and reduced quality of life (QOL), both of which elevate risk of death and hospitalization in patients with HFpEF. Supervised exercised training is associated with improvements in exercise capacity and QOL in adults with HFpEF. However, supervised exercise has not been widely utilized for the treatment of HFpEF due to logistical and fiscal barriers. Home-based exercise using an m-Health platform is an alternative to supervised exercise that can deliver clinician prescribed exercise interventions and wellness education though monitoring and care coordination. The goal of this study is to evaluate the feasibility and efficacy of a patient specific progressive home-based cardiac rehabilitation program leveraging the technology of the m-Health program in improving functional status, exercise capacity, and QOL in patients with HFpEF.
• Adults age> 18 years
• HFpEF with left ventricular ejection fraction >50%
• Clinically stable and no hospitalization in last 4 weeks
• Estimated glomerular filtration rate > 45 mL/min/1.73 m2 as measured by the simplified MDRD formula
• Stable diuretic regimen Exclusion criteria:
• History of cancer or end stage lung disease
• Estimated glomerular filtration rate < 45 mL/min/1.73 m2 as measured by the simplified MDRD formula
• Recent HF decompensation
• Inability to do exercise test
• Inability to provide written informed consent
• History of falls
Olanzapine Versus Megestrol Acetate for the Treatment of Loss of Appetite Among Advanced Cancer Patients
This phase III trial compares the effects of olanzapine versus megestrol acetate in treating loss of appetite in patients with cancer that has spread to other places in the body (advanced). Olanzapine may stimulate and increase appetite. This study aims to find out if olanzapine is better than the usual approach (megestrol acetate) for stimulating appetite and preventing weight loss.
• Women and men of reproductive potential should agree to use an appropriate method of birth control throughout their participation in this study due to the teratogenic potential of the therapy utilized in this trial. Appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives or double barrier method (diaphragm plus condom)
• Diagnosis of advanced cancer
• Patient-reported 2-month weight loss of at least 5 pounds (2.3 kilograms) and/or physician-estimated caloric intake of less than 20 calories/kilogram of body weight per day
• The patient must perceive loss of appetite and/or weight as a problem; and have an appetite score of 4 or worse on the "Please rate your appetite…." question that requires a patient response on a 0-10 numeric rating scale
• Not receiving ongoing tube feedings or parenteral nutrition at the time of registration
• Not currently using systemic adrenal steroids (with the exception of short-term dexamethasone within 3 days of chemotherapy for control of chemotherapy side effects)
• No use of androgens, progesterone analogs, or other appetite stimulants within the past month
• Patient should not have poorly controlled hypertension or congestive heart failure at registration
• Patient should not have an obstruction of the alimentary canal, malabsorption, or intractable vomiting (defined as vomiting more than 3 times per day over the preceding week)
• Not currently using olanzapine for another medical condition or had previously used olanzapine for chronic nausea or for any pre-existing psychotic disorder
• Patient should not have had a previous blood clot at any time in the past
• No history of poorly controlled diabetes
• No symptomatic leptomeningeal disease or known brain metastases as these patients may have difficulty taking oral medications
• No history of hypersensitivity to olanzapine or megestrol acetate
• No COVID-19 infection in the past that, in the opinion of the treating physician, had left patients with compromised taste, which has not resolved at the time of registration
• Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown. Therefore, for women of childbearing potential only, a negative urine or serum pregnancy test done =< 14 days prior to registration is required
• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
• Estimated life expectancy of 3 months or longer
• Serum creatinine =< 2.0 mg/dL
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 3 x upper limit of normal (ULN)
• Fasting glucose < 140 mg/dL
• Granulocytes > 1000/hpf
• No treatment with another antipsychotic agent, such as risperidone, quetiapine, clozapine, butyrophenone within 30 days of enrollment
• In order to complete the mandatory patient-completed measures, participants must be able to speak and/or read English or Spanish. Sites seeking to enroll Spanish-speaking patients should have access to Spanish speaking staff on site or through the use of a translation service to be able to conduct the informed consent discussion in Spanish, and to conduct the weekly phone calls
• Psychiatric illness which would prevent the patient from giving informed consent
• Medical condition such as uncontrolled infection (including human immunodeficiency virus [HIV]), uncontrolled diabetes mellitus or cardiac disease which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient
• Patients who cannot swallow oral formulations of the agents
• Patients with impaired decision-making capacity (such as with a diagnosis of dementia or memory loss) are not eligible for this study
• No presence of a hormone-sensitive tumor, such as breast, endometrial, or prostate cancer (this exclusion criterion is intended to circumvent any confounding antineoplastic effects of megestrol acetate)
A Study of Tirzepatide (LY3298176) in Participants With Heart Failure With Preserved Ejection Fraction and Obesity (SUMMIT)
The main purpose of this study is to assess the efficacy and safety of Tirzepatide (LY3298176) in participants with heart failure with preserved ejection fraction and obesity.
• Have a diagnosis of stable heart failure (NYHA class II-IV) and left ventricular ejection fraction (LVEF) ≥50%
• Elevated NT-proBNP (N-terminal pro B-type natriuretic peptide) > 200 pg/ml for participants without atrial fibrillation (AF), or >600 picogram/milliliter (pg/ml) for participants with AF, Structural heart disease (Left atrial enlargement) or Elevated left ventricular filling pressure
• Estimated glomerular filtration rate (eGFR) <70 milliliter (ml)/minute (min)/1.73m² at screening, or HF decompensation within 12 months of screening,
• Stable dose of heart failure medications within 4 weeks of screening
• Body mass index (BMI) ≥30 kilograms per meter squared (kg/m²)
• 6MWD 100-425m
• KCCQ CSS ≤80
• Have had a major cardiovascular event within the last 90 days of screening
• Have had acute decompensated heart failure within 4 weeks of screening
• Have non cardiac causes of functional impairment such as pulmonary arterial hypertension (PAH), severe chronic obstructive pulmonary disease (COPD), anemia, thyroid disease, musculoskeletal disease or orthopedic conditions
• Presence of cardiac amyloidosis, cardiac accumulation disease, cardiomyopathy and severe valvular hear disease
• HbA1c ≥9.5% or uncontrolled diabetes
• History of proliferative diabetic retinopathy or diabetic maculopathy
• Have a history of pancreatitis
• eGFR <15 mL/min/1.73 m² or requiring dialysis at screening
A Study to Learn About How Well Riociguat Works, How Safe it is and How it is Used Under Real World Conditions in Patients in the United States Who Are Receiving Riociguat for High Blood Pressure in the Arteries That Carry Blood From the Heart to the Lungs (Pulmonary Arterial Hypertension, PAH) (ROAR)
Pulmonary arterial hypertension (PAH) is a type of high blood pressure in the arteries that carry blood from the heart to the lungs. PAH occurs when the openings in the blood vessels of the lungs get smaller and smaller. These smaller openings can be caused by the following: - The walls of the arteries tightening - The walls of the arteries becoming stiff and narrow from an overgrowth of cells The increased pressure in the pulmonary arteries strains the right side of the heart and it begins to fail, causing difficulty breathing and other symptoms. As PAH progresses, symptoms get worse. There is no cure for PAH, but several medications like endothelin receptor antagonists (ERAs), prostacyclin analogues (PCAs) and riociguat, a soluable guanylate cyclase stimulator, are available to help slow the progression of changes in the pulmonary arteries and help reduce symptoms. Riociguat can be taken together with ERAs and PCAs. In this study, the researchers want to learn about how well riociguat works, how safe it is when patients take it in 1 of these ways: - alone - with ERA - with PCA - with ERA and PCA The dosage for each patient will be decided by their doctor. The researchers will review information collected from the patients who have decided with their doctor to start riociguat treatment for their PAH. The study will include about 500 patients in the United States who are at least 18 years old. All of the patients will have either just started taking riociguat or will have been taking it for less than 3 months No investigational products will be administered in this study. Patients will be treated with the Standard of Care (SOC) for PAH. The SOC is the currently appropriate treatment in accordance with scientific evidence and agreed upon in collaboration between medical experts for PAH. There will be no study-mandated visits or treatments. The patients will be in the study for up to 2 years. During this time, they will visit their doctor every 3 to 6 months as part of the Standard of Care. At these visits, the patients will answer questions about their PAH symptoms and whether they have any medical problems. They will also do exercise tests to see how well they are able to breathe and how tired they get while exercising. The doctors will perform other usual examinations which are part of the Standard of Care such as echocardiograms (images of the heart to show how the heart is working) and a right heart catheters (to measure the pressures in the heart) and will take the usual blood and urine samples.
• Patients aged ≥18 years at the time of riociguat treatment initiation
• Diagnosis of PAH per National Institute for Health and Care Excellence (NICE) 2018 classification
• Decision to initiate treatment with riociguat as per investigator's routine treatment practice made prior to enrollment in the study
• Initiation of riociguat, as per the FDA-approved US label:
• At enrollment OR
• ≤90 days prior to enrollment, with a documented titration regimen (defined as all documented dose changes including, but not limited to: starting dose and dates and highest tolerated dose and dates)
• Signed informed consent
• Previously treated with and discontinued use of riociguat for any reason prior to study enrollment (discontinuation defined as an interruption of therapy ≥30 days)
• Participating in any of the following:
• Blinded clinical trial
• Clinical trial involving an unapproved drug
• Investigational program with interventions outside of routine clinical practice
• Life expectancy <12 months
• Contraindicated to receive riociguat per the FDA approved US label
• Use of nitrates or NO donors in any form
• Use of PDE5 inhibitors
• PH associated with idiopathic interstitial pneumonias
• Unable or unwilling to provide informed consent
A Study of the Efficacy and Safety of MK-5475 in Participants With Pulmonary Arterial Hypertension (INSIGNIA-PAH: Phase 2/3 Study of an Inhaled sGC Stimulator in PAH) (MK-5475-007)
This is a two-part (Phase 2/Phase 3) study of MK-5475, an inhaled soluble guanylate cyclase stimulator, in participants with pulmonary arterial hypertension (PAH). The first part (Phase 2) will assess three different doses of MK-5475 compared to placebo in a base period of 12 weeks, followed by comparison of three different doses of MK-5475 during an optional 24 month extension period. The treatment dose with the best efficacy and safety profile in the phase 2 cohort base period will be selected for use in the second part (Phase 3) of the study. The primary hypothesis of Phase 2 is that at least one MK-5475 dose is superior to placebo in reducing pulmonary vascular resistance (PVR) from baseline at week 12. The purpose of the second part (Phase 3) of the study is to confirm the efficacy, safety, and tolerability of MK-5475 at the selected dose compared to placebo during a 12 week base period followed by an extension period of up to 5 years. The primary hypothesis of Phase 3 is that MK-5475 is superior to placebo in increasing 6-minute walk distance (6MWD) from baseline at week 12.
• Pulmonary arterial hypertension (PAH) in one of the following groups:
• Idiopathic PAH
• Heritable PAH
• Drug and toxin-induced PAH
• PAH associated with connective tissue disease, HIV infection, or congenital heart disease.
• Diagnosis of PAH documented by right heart catheterization (RHC).
• Eligibility RHC meeting all of the following criteria:
• Mean pulmonary artery pressure (mPAP) ≥25 mmHg
• Pulmonary vascular resistance (PVR) of ≥3 Wood units
• Pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure (LVEDP) ≤15 mmHg.
• World Health Organization functional class (WHO-FC) symptoms between Class II and IV.
• Two 6-Minute walk distance (6MWD) measurements between 150 and 500 meters, one at screening and one at randomization.
• Stable concomitant background PAH-specific therapy.
• Body Mass Index (BMI) between 18.5 kg/m² and 40 kg/m² .
• Agree to be abstinent from heterosexual intercourse or use contraception during the intervention period and for at least 14 days after the last dose of study intervention.
• Female participants may not be pregnant or breastfeeding.
• Group 2 to 5 pulmonary hypertension.
• PAH in one of the following groups:
• Long term responders to calcium channel blockers
• Overt features of venous/capillary involvement
• Evidence of more-than-mild obstructive lung disease.
• Evidence of more-than-mild parenchymal lung disease.
• Evidence of more-than-mild obstructive sleep apnea (OSA) that is untreated.
• Evidence or history of left heart disease, including any of the following:
• Left ventricular ejection fraction (LVEF) ≤45%
• Moderate or severe left-sided valvular disease (aortic or mitral valve stenosis or regurgitation)
• Significant left ventricular diastolic dysfunction on echocardiographic evaluation
• Presence of 3 or more of the following risk factors for heart failure with preserved ejection fraction: BMI>30 kg/m², essential systemic hypertension, diabetes mellitus of any type, or coronary artery disease.
• Oxygen saturation measured by pulse oximetry (SpO₂) <90%, despite supplemental oxygen therapy.
• Chronic renal insufficiency (eGFR <30 mL/min)
• Chronic liver disease (i.e., Child-Pugh B or C), portal hypertension, cirrhosis, or significant hepatic laboratory abnormalities.
• Current smoker or currently uses electronic cigarettes (vapes).
• History of cancer, except: nonmelanomatous skin carcinoma or carcinoma in situ of the cervix or other malignancies which have been successfully treated, with appropriate follow up, and unlikely to recur for the duration of the study.
FUVID Study: Functional Characterization of Children With Chronic Venous Thromboembolic Disease
This is a multi-center prospective cohort study of patients with first-episode deep venous thrombosis and pulmonary embolism.
• Ages 8 to ≤ 21 years
• Participant must be able to speak and understand English
• Be willing to participate and able to comply with the study protocol
• For participants with PE: Children with acute, radiologically confirmed pulmonary embolism (PE) with our without DVT
• For control group: Children who are prescribed physical activity restrictions for 2 up to 12 weeks following any minor outpatient surgery or, minor injury (surgery or injury is referred to as "diagnosis" hereafter)
• Congenital heart disease with abnormal pulmonary circulation or with in-situ pulmonary artery thrombosis
• Chronic kidney disease
• Chronic inflammatory or an autoimmune disorder (such as systemic lupus erythematosus, juvenile rheumatoid disorder, inflammatory bowel disease, and sickle cell disease)
• A metabolic or endocrinological disorder such as diabetes mellitus or thyroid disorder
• History of or active cancer
• Musculoskeletal limitations to exercise expected to be present uptil 4 months post-diagnosis
• Weight ≥ 300 lbs
• Contraindications to magnetic resonance imaging
• Frequent severe exacerbations of asthma defined by two or more bursts of systemic glucocorticoids (more than three days each) in the previous year or at least one hospitalization, intensive care unit stay or mechanical ventilation in the previous year. Patients should also be excluded if there are daily symptoms of asthma requiring daily use of short-acting bronchodilators such as albuterol or levalbuterol administration. The use of controller medications such as daily inhaled corticosteroids for mild persistent asthma is not exclusionary.
• Has any other medical condition, which in the opinion of the investigator may potentially compromise the safety or compliance of the patient or may preclude the patient's successful completion of the clinical study Additional exclusion criteria for participants with PE:
• Prior history of DVT or PE (upper extremity, cerebral sinus venous thrombosis and abdominal thromboses encountered as a neonate are not exclusion criteria)
• Lack of anticoagulant treatment for the acute VTE due to contraindications
Cancer and Blood Pressure Management, CARISMA Study
This phase II trial studies how well intensive blood pressure management works in decreasing systolic blood pressure in patients with kidney or thyroid cancer that has spread to other places in the body (metastatic) who are starting anti-angiogenic tyrosine kinase inhibitor cancer therapy. This study is being done to find out if a systolic blood pressure to a target of less than 120 mmHg (intensive systolic blood pressure management) can be achieved, well tolerated, and beneficial as compared to the usual approach to a target of less than 140 mmHg while taking an anti-angiogenic tyrosine kinase inhibitor. This study may help doctors understand the best way to control blood pressure in kidney or thyroid cancer patients taking anti-angiogenic tyrosine kinase inhibitor.
• English speaking
• Patient must have histologically or cytologically-proven advanced metastatic renal cell cancer (mRCC) or medullary thyroid cancer initially treated with anti-angiogenic tyrosine kinase inhibitors (AA-TKIs) including: sunitinib, sorafenib, pazopanib, cabozantinib, lenvatinib, vandetanib, or axitinib)
• NOTE: If patient has a severe sulfa allergy (e.g. Stevens Johnson reaction), then alternative non-sulfa medications can be considered in consultation with the C-BAC. Patient with a noted severe allergic reactions to medications listed in the algorithms is not necessarily excluded from this trial, as alternative medications could be considered in consultation with the C-BAC. Moreover, the patient treated with pre-existing medications that may interact with proposed BP medications is not necessarily excluded, as alternative medications exist. The clinical significance of any potential drug interactions can also be addressed with the C-BAC.
• Prior exposure to another AA-TKI is permissible. Concurrent or prior treatment with immunotherapy is also permissible
• Patient must have either clinical cardiovascular (CV) disease or evidence of increased CV risk as defined by one or more of the following:
• Clinical CV disease (history of myocardial infarction [MI] acute coronary syndrome, coronary revascularization, carotid endarterectomy or stenting greater than 3 months prior to registration, peripheral artery disease, cerebrovascular accident greater than 3 months prior to registration, abdominal aortic aneurysm or heart failure [HF])
• An American College of Cardiology/American Heart Association (ACC/AHA) CV risk score of at least 10%
• Chronic kidney disease (defined as an estimated glomerular filtration rate [eGFR] between 30 and 60 ml/min per 1.73 m^2). Dialysis patients and patients with an eGFR < 30 ml/min/1.73m^2 will be excluded. eGFR will be calculated according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) equation
• Patient must have systolic blood pressure (SBP) >= 130 mmHg on two or more occasions according to any in-clinic visit in the 12 weeks prior to or during their initial 4 weeks of treatment with an AA-TKI. Patient who have a prior diagnosis of hypertension or on pre-existing anti-hypertensive medications are eligible for enrollment. However, patient must not be on more than 3 baseline blood pressure medications at time of entry
• NOTE: If a patient has a single elevated SBP >= 130mmHg but not on repeat assessment, an additional SBP assessment should be performed to confirm ineligibility
• Patient must agree to comply with performing home blood pressure monitoring using an Omron7250 oscillometric monitor at home, or equivalent models
• Women of childbearing potential and sexually active males must be strongly advised to use accepted and effective methods of contraception or to abstain from sexual intercourse for the duration of their participation in the study
• Patient must have internet access through a computer, tablet, or smart phone to use EASEE-PRO and home BP monitoring. A valid phone number to receive text messages and email address are also necessary
• Leukocytes >= 3,000/mcL (obtained within 14 days prior to registration)
• Absolute neutrophil count >= 1,500/mcL (obtained within 14 days prior to registration)
• Platelets >= 100,000/mcL (obtained within 14 days prior to registration)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal (ULN) (obtained within 14 days prior to registration)
• Patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• Patient with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• Patient with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
• Patient with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy
• Patient with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Patient must not have end-stage renal failure on dialysis, history of repeated hyperkalemia with a potassium > 5.5 mEq/l, or have a kidney transplant, or an eGFR < 30 ml/min/1.73 m^2
• Patient must not have coronary artery bypass grafting, MI acute coronary syndrome severe/unstable angina, stroke, transient ischemic attack, clinically significant bleeding requiring hospitalization or pulmonary embolism within 3 months prior to registration
• Patient must not have brain surgery or radiotherapy within 2 weeks prior to registration
• Patient must not have uncontrolled blood pressure defined by SBP > 160 mmHg on three or more antihypertensives prior to TKI initiation
• Patient with an arm circumference too large (> 50 cm) or small (< 17 cm) to allow accurate BP measurement with available devices will not be eligible
• Women must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with some anti-hypertensives, including angiotensin receptor blockers. All females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy. A female of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: has achieved menarche at some point, has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
Influence of Cooling Duration on Efficacy in Cardiac Arrest Patients (ICECAP)
A multicenter, randomized, adaptive allocation clinical trial to determine if increasing durations of induced hypothermia are associated with an increasing rate of good neurological outcomes and to identify the optimal duration of induced hypothermia for neuroprotection in comatose survivors of cardiac arrest.
• Coma after resuscitation from out of hospital cardiac arrest
• Cooled to <34 deg C with 240 minutes of cardiac arrest
• Definitive temperature control applied
• Age ≥ 18 years
• Informed consent from legal authorized representative (LAR) including intent to maintain life support for 96 hours
• Enrollment within 6 hours of initiation of cooling
• Hemodynamic instability
• Pre-existing neurological disability or condition that confounds outcome determination
• Pre-existing terminal illness, unlikely to survive to outcome determination
• Planned early withdrawal of life support
• Presumed sepsis as etiology of arrest
A Study Evaluating the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in PAH Patients
Study ROR-PH-301, ADVANCE OUTCOMES, is designed to assess the efficacy and safety of ralinepag when added to pulmonary arterial hypertension (PAH) standard of care or PAH-specific background therapy in subjects with World Health Organization (WHO) Group 1 PAH.
• At least 18 years of age.
• Evidence of a personally signed and dated informed consent form indicating that the subject has been informed of all pertinent aspects of the study prior to initiation of any study-related procedures.
• Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
• Primary diagnosis of symptomatic PAH.
• Has had a right heart catheterization (RHC) performed at or within 3 years prior to Screening (RHC will be performed during Screening if not available) that is consistent with the diagnosis of PAH.
• Has WHO/ NYHA functional class II to IV symptoms.
• If on PAH-specific background oral therapy, subject is on stable therapy with either an endothelin receptor antagonist (ERA) and/or a phosphodiesterase type 5 inhibitor (PDE5-I) or a soluble guanylate cyclase (sGC) stimulator.
• Has a 6MWD of ≥150 meters.
• If taking concomitant medications that may affect the clinical manifestations of PAH (eg, calcium channel blockers, diuretics, digoxin, or L arginine supplementation, beta blockers, angiotensin-converting enzyme inhibitors, or angiotensin II receptor blockers), must be on a stable dose for at least 30 days prior to the Baseline Visit and the dosage maintained throughout the study. The exception is that the dose of diuretics must be stable for at least the 10 days prior to Baseline.
• Both male and female subjects agree to use a highly effective method of birth control throughout the entire study period from informed consent through to the 30-Day Follow-up Visit, if the possibility of conception exists. Eligible male and female subjects must also agree not to participate in a conception process during the study and for 30 days after the last dose of IMP. Eligible male subjects must agree not to participate in sperm donation for 90 days after the last dose of IMP.
• For subjects with known HIV-associated PAH, a cluster designation 4 (CD4+) T-cell count <200/mm3 within 90 days of Baseline.
• Must not have 3 or more left ventricular dysfunction risk factors as defined in the study protocol.
• Has evidence of more than mild lung disease on pulmonary function tests performed within 180 days prior to, or during Screening.
• Has evidence of thromboembolic disease as determined by a V/Q lung scan or local standard of care diagnostic evaluation at or after diagnosis of PAH.
• Current diagnosis of ongoing and clinically significant sleep apnea as defined by the Investigator.
• Male subjects with a corrected QT interval using Fridericia's formula (QTcF) >450 msec and female subjects with a QTcF >470 msec on ECG recorded at Screening and analyzed by the central ECG laboratory. Subjects with evidence of intraventricular conduction delay, defined as a QRS interval greater than 110 msec, will be excluded if the QTcF is >500 msec for both males and females.
• Severe chronic liver disease (ie, Child-Pugh Class C), portal hypertension, cirrhosis or complications of cirrhosis/portal hypertension (eg, history of variceal hemorrhage, encephalopathy).
• Confirmed active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).
• Subjects with alanine aminotransferase or aspartate aminotransferase ≥3 times the upper limit of normal (ULN) or total bilirubin ≥2 × ULN at Screening.
• Chronic renal insufficiency as defined by serum creatinine >2.5 mg/dL or requiring dialysis at Screening.
• Hemoglobin concentration <9 g/dL at Screening.
• Subjects treated with an IV or SC prostacyclin pathway agent (eg, epoprostenol, treprostinil, or iloprost) for PAH at any time prior to Baseline (use in vasoreactive testing is permitted).
• Subjects currently on or who were treated with an inhaled or oral prostacyclin pathway agent (iloprost, treprostinil, beraprost, or selexipag) for >6 months or within 90 days prior to Baseline.
• Subject has pulmonary veno-occlusive disease.
• Malignancy diagnosed and/or treated within 5 years prior to Screening, with the exception of localized non-metastatic basal cell or squamous cell carcinoma of the skin or in-situ carcinoma of the cervix excised with curative intent.
• Subject tests positive for amphetamine, cocaine, methamphetamine, methylenedioxymethamphetamine or phencyclidine in urine drug screen performed at Screening, or has a recent history (6 months) of alcohol or drug abuse. A subject will not be excluded due to a positive drug screen caused by prescribed medications.
• Initiation or discontinuation of a cardio-pulmonary rehabilitation program based upon exercise within 90 days prior to Screening and/or planned during study participation.
• Prior participation in any study of ralinepag or participation in another interventional clinical study with medicinal products within 30 days prior to Screening. Concurrent participation in registry or observational studies is allowed, as long as the subject can fulfill all other entry criteria and comply with all study procedures.
• Any reason that, in the opinion of the Investigator or Medical Monitor, precludes the subject from participating in the study (eg, any previous or intercurrent medical condition) that may increase the risk associated with study participation or that would confound study analysis or impair study participation or cooperation.
• Known hypersensitivity to ralinepag or any of the excipients.
• Life expectancy <12 months based on the Investigator's opinion.
• Women who are pregnant, lactating or breast-feeding.
Stereotactic Radiosurgery (SRS) Dose-Escalation Study for Brain Metastasis (SRS)
SRS dose escalation for brain metastases in radiation-naïve patients will establish true tolerable doses, which may exceed the current standard doses. This may lead to an improvement in local control, patient survival, and/or quality-of life.
• Biopsy-proven non-hematopoietic malignancy, except for small cell lung cancer, germ cell cancer, or unknown primary tumor.
• Radiographic evidence by MRI (or by CT scan with CT contrast if ineligible or intolerant of MRI) of brain metastasis. (If patient is unable to tolerate MRI contrast, an MRI without contrast is acceptable if lesions are visible)
• All brain metastases must be outside the brain stem (midbrain, pons and medulla).
• Patient must have 10 or less brain metastases.
• The maximum diameter of any lesion must be less than or equal to 3.0 cm.
• Previous treatment with surgery, radiation, chemotherapy, immunotherapy or any targeted agents are allowed provided that:
• Radiation was not to the brain.
• Surgery to the brain was > 7 days prior to SRS and there remains at least one additional brain metastasis that can be targeted with SRS
• Age ≥ 18 years.
• ECOG Performance Score of 2 or better/Karnofsky Performance Status score of 50-60 or better.
• All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months). Medically acceptable birth control (contraceptives) includes:
• Approved hormonal contraceptives (such as birth control pills, patch, or ring: Depo-Provera, Implanon), or
• Barrier methods (such as a condom or diaphragm) used with a spermicide (a substance that kills sperm)
• Ability to understand and the willingness to sign a written informed consent. Exclusion Criteria
• Patients had craniotomy and surgery to the brain within 7 days from the date of SRS.
• Patients with leptomeningeal metastasis. NOTE: For the purposes of exclusion, LMD is a clinical diagnosis, defined as positive CSF cytology and/or equivocal radiologic or clinical evidence of leptomeningeal involvement. Patients with leptomeningeal symptoms in the setting of leptomeningeal enhancement by imaging (MRI) would be considered to have LMD even in the absence of positive CSF cytology, unless a parenchymal lesion can adequately explain the neurologic symptoms and/or signs. In contrast, an asymptomatic or minimally symptomatic patient with mild or nonspecific leptomeningeal enhancement (MRI) would not be considered to have LMD. In that patient, CSF sampling is not required to formally exclude LMD, but can be performed at the investigator's discretion based on level of clinical suspicion.
• Patients with a contraindication to both MRI (with or without contrast) and CT scan (with contrast)
• Patients with life expectancy < 3 months.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
• Subjects must not be pregnant or nursing at the time of SRS treatment due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
Milrinone in Congenital Diaphragmatic Hernia
Infants with congenital diaphragmatic hernia (CDH) usually have pulmonary hypoplasia and persistent pulmonary hypertension of the newborn (PPHN) leading to hypoxemic respiratory failure (HRF). Pulmonary hypertension associated with CDH is frequently resistant to conventional pulmonary vasodilator therapy including inhaled nitric oxide (iNO). Increased pulmonary vascular resistance (PVR) can lead to right ventricular overload and dysfunction. In patients with CDH, left ventricular dysfunction, either caused by right ventricular overload or a relative underdevelopment of the left ventricle, is associated with poor prognosis. Milrinone is an intravenous inotrope and lusitrope (enhances cardiac systolic contraction and diastolic relaxation respectively) with pulmonary vasodilator properties and has been shown anecdotally to improve oxygenation in PPHN. Milrinone is commonly used during the management of CDH although no randomized trials have been performed to test its efficacy. Thirty percent of infants with CDH in the Children's Hospital Neonatal Database (CHND) and 22% of late-preterm and term infants with CDH in the Pediatrix database received milrinone. In the recently published VICI trial, 84% of patients with CDH received a vasoactive medication. In the current pilot trial, neonates with an antenatal or postnatal diagnosis of CDH will be randomized to receive milrinone or placebo to establish safety of this medication in CDH and test its efficacy in improving oxygenation.
• ≥ 36 0/7 weeks PMA by best obstetric estimate AND birth weight of ≥ 2000g
• postnatal age ≤7 days (168 hours of age)
• invasive mechanical ventilation (defined as ventilation with an endotracheal tube) and
• one arterial blood gas with an OI ≥ 10 (after tracheal tube obstruction and other easily resolvable mechanical causes for increased OI are ruled out) on the most recent arterial blood gas within 12 hours prior to the time of randomization.
• if an arterial blood gas is not available at the time of randomization, a preductal OSI of ≥ 5 can be used as an inclusion criterion instead of OI ≥ 10; (the OSI should be based on the most recent preductal pulse oximetry recording and must be within 12 hours of randomization)
• postnatal blood gas with PCO2 ≤ 80 mmHg (arterial, capillary or venous blood gas) on the most recent blood gas sample obtained within 12 hours prior to randomization Note: Criteria (iv) to (vi) must be met at the most recent analysis within 12 hours prior to randomization.
• known hypertrophic cardiomyopathy
• Note 1: infants of diabetic mothers with asymmetric septal hypertrophy can be included as long as there is no evidence of obstruction to left ventricular outflow tract on echocardiogram,
• Note 2: infants with other acyanotic congenital heart disease (CHD) and CDH may be included in the study and will be a predetermined subgroup for analysis)
• cyanotic CHD - transposition of great arteries (TGA), total anomalous pulmonary venous return (TAPVR), partial anomalous pulmonary venous return (PAPVR), truncus arteriosus (TA), tetralogy of Fallot (TOF), single ventricle physiology - hypoplastic left heart syndrome (HLHS), tricuspid atresia, critical pulmonic stenosis or atresia etc.,
• enrolled in conflicting clinical trials (such as a randomized controlled blinded trial of another pulmonary vasodilator therapy); Note: mothers enrolled in fetal tracheal occlusion studies such as FETO may be enrolled if permitted by investigators of the fetal tracheal occlusion study; [FETO refers to fetoscopic endoluminal tracheal occlusion and involves occlusion of fetal trachea with a balloon device at mid-gestation and subsequent removal in later gestation]
• infants with bilateral CDH o Note 3: infants with anterior and central defects are included in the study
• associated abnormalities of the trachea or esophagus (trachea-esophageal fistula, esophageal atresia, laryngeal web, tracheal agenesis)
• renal dysfunction (with serum creatinine > 2 mg/dL not due to maternal factors) or severe oligohydramnios associated with renal dysfunction at randomization; renal dysfunction may be secondary to renal anomalies or medical conditions such as acute tubular necrosis
• severe systemic hypotension (mean blood pressure < 35 mm Hg for at least 2 h with a vasoactive inotrope score of > 30)
• decision is made to provide comfort/ palliative care and not full treatment
• Intracranial bleed (including the following findings on the cranial ultrasound)
• Cerebral parenchymal hemorrhage
• Blood/echodensity in the ventricle with distension of the ventricle
• Periventricular hemorrhagic infarction
• Posterior fossa hemorrhage
• Cerebellar hemorrhage
• persistent thrombocytopenia (platelet count < 80,000/mm3) despite blood product administration on the most recent blood draw prior to randomization
• coagulopathy (PT INR > 1.7) despite blood product administration on the most recent blood draw (if checked - there is no reason to check PT for the purpose of this study)
• aneuploidy associated with short life span (such as trisomy 13 or 18) will not be included in the study (infants with trisomy 21 can be included in the study)
• elevated arterial, venous or capillary PCO2 > 80 mmHg in spite of maximal ventilator support (including high frequency ventilation) on the most recent blood gas obtained within 12 hours prior to randomization
• use of milrinone infusion prior to randomization (the use of other inhaled pulmonary vasodilators such as iNO, inhaled epoprosternol, inhaled PGE1 and oral such as endothelin receptor antagonists is permitted - Note: it is unlikely to be on oral pulmonary vasodilators early in the course of CDH)
• ongoing therapy with parenteral (intravenous or subcutaneous) pulmonary vasodilators such as IV/SQ prostacyclin analogs (Epoprostenol - Flolan or Treprostinil - Remodulin or PGE1 - Alprostadil) or IV phosphodiesterase 5 inhibitors (sildenafil - Revatio) at the time of randomization. In addition, initiation of therapy with these two classes of parenteral medications during the first 24 hours of study drug initiation is not permitted and will be considered a protocol deviation. The risk of systemic hypotension is high during the first 24 hours of study-drug (milrinone) infusion and hence parenteral administration of other pulmonary vasodilators is avoided to minimize risk of hypotension.
• Subjects already on ECMO or patients who are being actively considered for ECMO by the neonatal or surgical team
• attending (neonatal, critical care or surgical) refusal for participation in the trial (including concern about presence of hemodynamic instability)
Study to Determine the Pharmacokinetics and Pharmacodynamic Effects of Phenylephrine on BP Via IV
The primary objective of this study is to evaluate the dose effect of Phenylephrine Hydrochloride Injection on the treatment of clinically relevant decreased blood pressure in the pediatric population, ≥12 to 16 year old patients undergoing general and neuraxial anesthesia. The secondary objectives are to describe changes in blood pressure and heart rate, time to onset and to maximal response, and the duration of response; to assess the safety of the product in this population; and to characterize the pharmacokinetics of phenylephrine hydrochloride.
• Subject's age is between ≥12 and 16 years, inclusive
• Subject is scheduled for a procedure that requires general or neuraxial anesthesia
• Subjects must have normal or clinically acceptable physical exam
• Subjects with controlled diabetes prior to entry must have a mean systolic/diastolic office blood pressure ≤128/78 mmHg (sitting, after 5 minutes of rest)
• Females must have a urine or serum pregnancy test (Human Chorionic Gonadotropin) that is negative at Screening and Day 1
• Subject's parent or legal guardian gives informed consent and subject gives assent.
• Subject has a contraindication to vasoconstrictor therapy for control of blood pressure
• Subject has participated in other clinical trials for investigational drugs and/or devices within 30 days prior to enrollment
• Subject has any serious medical condition which, in the opinion of the investigator, is likely to interfere with study procedures
• Subjects who have a history of any clinically significant local or systemic infectious disease within four weeks prior to initial treatment administration
• Subjects who are positive for hepatitis B surface antigen or hepatitis C antibody
• Subjects taking antihypertensive medication
• Subject is moribund (death is likely to occur in less than 48 hours)
• Females who are pregnant, nursing or unwilling to use/practice adequate contraception.
Multicenter Trial of Congenital Pulmonic Valve Dysfunction Studying the SAPIEN 3 THV With the Alterra Adaptive Prestent (ALTERRA)
To demonstrate the safety and functionality of the Edwards Alterra Adaptive Prestent in conjunction with the Edwards SAPIEN 3 Transcatheter Heart Valve (THV) System in patients with a dysfunctional right ventricular outflow tract/pulmonary valve (RVOT/PV) who are indicated for treatment of pulmonary regurgitation (PR).
• The patient/patient's legally authorized representative has been informed of the nature of the study, agrees to its provisions and has provided written informed consent.
• Pediatric or adult patent whose weight is ≥ 20 kg (44 lbs).
• The patient has a dysfunctional RVOT/PV.
• RVOT/PV proximal and distal landing zone diameter ≥ 27 mm and ≤ 38 mm and/or minimum of 35 mm from contractile tissue to lowest pulmonary artery takeoff immediately prior to Alterra Prestent insertion.
• Active infection requiring current antibiotic therapy (if temporary illness, patient may be a candidate 2 weeks after discontinuation of antibiotics).
• History of or active endocarditis (active treatment with antibiotics) within the past 180 days.
• Leukopenia (WBC < 2000 cells/μL), anemia (Hgb < 7 g/dL), thrombocytopenia (platelets < 50,000 cells/μL) or any known blood clotting disorder.
• Inappropriate anatomy for introduction and delivery of the Alterra Adaptive Prestent or the SAPIEN 3 THV.
AtRial Cardiopathy and Antithrombotic Drugs In Prevention After Cryptogenic Stroke (ARCADIA)
Objectives - Primary: To test the hypothesis that apixaban is superior to aspirin for the prevention of recurrent stroke in patients with cryptogenic ischemic stroke and atrial cardiopathy. - Secondary: To test the hypothesis that the relative efficacy of apixaban over aspirin increases with the severity of atrial cardiopathy.
• Age ≥ 45 years.
• Clinical diagnosis of ischemic stroke + brain imaging to rule out hemorrhagic stroke.
• Modified Rankin Scale (MRS) score ≤ 4.
• Ability to be randomized within 3 to 180 days after stroke onset.
• ESUS, defined as all of the following:
• Stroke detected by CT or MRI that is not lacunar. Lacunar is defined as a subcortical (this includes pons and midbrain) infarct in the distribution of the small, penetrating cerebral arteries whose largest dimension is ≤1.5 cm on CT or ≤2.0 cm on MRI diffusion images/<1.5 cm on T2 weighted MR images. The following are not considered lacunes: multiple simultaneous small deep infarcts, lateral medullary infarcts, and cerebellar infarcts. Patients with a clinical lacunar stroke syndrome and no infarct on imaging are excluded.
• Absence of extracranial or intracranial atherosclerosis causing ≥50 percent luminal stenosis of the artery supplying the area of ischemia. Patients must undergo vascular imaging of the extracranial and intracranial vessels using either catheter angiography, CT angiogram (CTA), MR angiogram (MRA), or ultrasound, as considered appropriate by the treating physician and local principal investigator.
• No major-risk cardioembolic source of embolism, including intracardiac thrombus, mechanical prosthetic cardiac valve, atrial myxoma or other cardiac tumors, moderate or severe mitral stenosis, myocardial infarction within the last 4 weeks, left ventricular ejection fraction <30 percent, valvular vegetations, or infective endocarditis). Patent foramen ovale is not an exclusion. All patients must undergo electrocardiogram, transthoracic or transesophageal echocardiography (TTE or TEE) and at least 24 hours of cardiac rhythm monitoring (Holter monitor or telemetry or equivalent). Additional cardiac imaging, such as cardiac MRI, or cardiac CT will be performed at the discretion of the local treating physician and principal investigator. Additional cardiac rhythm monitoring, such as monitored cardiac outpatient telemetry (MCOT) or an implanted cardiac monitor, will be at the discretion of the treating physician and local principal investigator.
• No other specific cause of stroke identified, such as arteritis, dissection, migraine, vasospasm, drug abuse, or hypercoagulability. Special testing, such as toxicological screens, serological testing for syphilis, and tests for hypercoagulability, will be performed at the discretion of the treating physician and local principal investigator.
• History of atrial fibrillation (AF), AF on 12-lead ECG, or any AF of any duration during heart-rhythm monitoring prior to randomization.
• Clear indication for treatment-dose anticoagulant therapy, such as venous thromboembolism or a mechanical heart valve.
• Need for antiplatelet agent, such as aspirin or clopidogrel
• History of spontaneous intracranial hemorrhage.
• Chronic kidney disease with serum creatinine ≥2.5 mg/dL.For Canadian sites only, estimated creatinine clearance (eCrCl) <15 mL/min is also an exclusion criterion.
• Active hepatitis or hepatic insufficiency with Child-Pugh score B or C.
• Clinically significant bleeding diathesis.
• Unresolved anemia (hemoglobin <9 g/dL) or thrombocytopenia (<100 x 10E9/L).
• Clinically significant gastrointestinal bleeding within the past year (e.g., not due to external hemorrhoids).
• At risk for pregnancy: premenopausal or postmenopausal woman within 12 months of last menses without a negative pregnancy test or not committing to adequate birth control, which includes an oral contraceptive, two methods of barrier birth control such as condom with or without spermicidal lubricant + diaphragm, or abstinence.
• Known allergy or intolerance to aspirin or apixaban.
• Concomitant participation in another clinical trial involving a drug or acute stroke intervention.
• Considered by the investigator to have a condition that precludes follow-up or safe participation in the trial.
• Inability of either participant or surrogate to provide written, informed consent for trial participation.
Tacrolimus/Everolimus vs. Tacrolimus/MMF in Pediatric Heart Transplant Recipients Using the MATE Score (TEAMMATE)
The TEAMMATE Trial will enroll 210 pediatric heart transplant patients from 25 centers at 6 months post-transplant and follow each patient for 2.5 years. Half of the participants will receive everolimus and low-dose tacrolimus and the other half will receive tacrolimus and mycophenolate mofetil. The trial will determine which treatment is better at reducing the cumulative risk of coronary artery vasculopathy, chronic kidney disease and biopsy proven-acute cellular rejection without an increase in graft loss due to all causes (e.g. infection, PTLD, antibody mediated rejection).
• Orthotopic heart transplantation
• Age < 21 years at time of transplant
• Stable immunosuppression at the time of randomization with no contraindication to everolimus, tacrolimus, or mycophenolate mofetil
• Planned follow-up at a study site for the 30 month duration of the study.
• Subject or legal adult representative capable of providing informed consent (in general, assent will be sought for children aged 12 years or older).
• Multi-organ transplant (e.g. heart-lung or heart-liver).
• Known hypersensitivity to everolimus, sirolimus, tacrolimus or mycophenolate mofetil (MMF), or to components of the drug products.
• Patients on maintenance corticosteroid therapy exceeding a dose equivalent of prednisone 0.1 mg/kg/day at randomization.
• High-risk for rejection defined as active rejection, recurrent (≥ 2 episodes of grade 2R rejection) cellular rejection, recurrent rejection (≥ 2 episodes of any grade) with hemodynamic compromise, steroid-resistant rejection or unresolved antibody-mediated rejection during the first 6 months post-heart transplant
• Graft dysfunction (LVEF <40% or wedge pressure >22 mmHg or cardiac index <2.2 L/min/m2)
• Stage 4 or 5 CKD (eGFR <30 ml/min/1.73 m2) or moderate proteinuria (urine protein to urine creatinine ratio >0.5 mg/mg).
• Active infection requiring hospitalization or treatment dose medical therapy.
• Patients with ongoing wound healing problems, clinically significant wound infection requiring continued therapy or other severe surgical complication in the opinion of the Site Principal Investigator.
• Fasting Serum Cholesterol ≥300 mg/dL OR greater than or equal to 7.75 mmol/L, AND fasting triglycerides ≥2.5x the upper limit of normal (ULN). Note: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication, and reduction of serum cholesterol and triglyceride levels to below exclusion ranges is confirmed.
• Uncontrolled diabetes mellitus.
• Diagnosis of post-transplant lymphoproliferative disorder (PTLD) during the first 6 months post-heart transplant.
• History of non-adherence to medical regimens.
• Patients who are treated with drugs that are strong inducers or inhibitors of cytochrome P450 3A4 (CYP3A4) and cannot discontinue the treatment
• Patients who are pregnant or breast-feeding or intend to get pregnant during the study period.
Optimal Delay Time to Initiate Anticoagulation After Ischemic Stroke in Atrial Fibrillation (START)
Title: Optimal Delay Time to Initiate Anticoagulation after Ischemic Stroke in Atrial Fibrillation (START): a pragmatic, adaptive randomized clinical trial. Primary Objective: • To determine the optimal time to initiate anticoagulation with a Non-Vitamin K Oral Anticoagulant (NOAC) after ischemic stroke in patients with non-valvular atrial fibrillation. Secondary Objectives: - To compare the rates of primary adverse outcomes in a per protocol analysis - To compare 30 day clinical outcomes by the modified Rankin scale among the time-to-treatment groups - To compare 30 day clinical outcomes by the PROMIS-10 scale among the time-to-treatment groups. - To compare 90 day clinical outcomes by the modified Rankin scale among the time-to-treatment groups - To explore the optimal timing in subgroups of age, sex, outcome category, and NOAC choice
• New disabling neurological deficit attributable to new ischemic stroke.
• Minimum lesion diameter of 1.5cm on qualifying imaging. If lesion not visible on imaging, NIHSS must be greater than 4.
• Non-valvular atrial fibrillation (paroxysmal, persistent, or permanent).
• Not currently anticoagulated and/or will not be anticoagulated prior to starting their NOAC at the randomized time of initiation (except for DVT prophylaxis). Note: Patients who had been taking an anticoagulant prior to their qualifying index event (for any reason) are eligible for START, assuming the drug is no longer having a therapeutic effect in the patient's system by 48 hours from stroke onset.
• Treating physician plans to anticoagulate with a FDA-approved novel oral anticoagulant (NOAC): apixaban, dabigatran, edoxaban, or rivaroxaban, or other FDA-approved NOAC.
• Qualifying brain CT or MRI scan < 48hr from stroke onset (time last known well). If patient has been treated with thrombolytic or endovascular therapy for this stroke, then the qualifying scan is that which is performed after therapy to rule out clinically significant hemorrhagic transformation.
• Ability to randomize within 60 hours of symptom onset.
• Any clinical or imaging evidence of spontaneous intracranial hemorrhage in the previous 6 months. Note: Patients with hemorrhagic transformation of current or previous ischemic stroke may be included per Investigator's judgment. Sporadic microbleeds may be included per Investigator's judgment. As a general recommendation, a cerebral microbleed is considered to be ≤ 5mm, but sometimes up to 10mm, in greatest diameter on gradient recalled echo (GRE), or T2*, MRI sequences. Any blood visualized on a CT will be classified as a macrobleed.
• Infarct volume (estimated) is greater than 50% of middle cerebral artery territory on qualifying scan. If the full extent of the lesion is not visible, any patient with a NIHSS > 23 must be excluded. Note: The lesion does not need to be restricted to the mCA, but if the lesion volume is estimated to be greater than half of the mCA territory, the patient should be excluded. Note: In non-EVT patients, any NIHSS following the index stroke may be used to qualify the patient for START. For example, a patient that presents with a NIHSS of 10 who then receives tPA and improves to a NIHSS of 2 is still eligible for START. For patients whom had endovascular therapy, the qualifying NIHSS assessment is that which is obtained with their qualifying scan following therapy.
• Anticipated need for major surgery over the next 30 days that would require delay, discontinuation, or extended suspension of anticoagulant of more than 5 days.
• Symptomatic edema expected from size and location of ischemic stroke.
• Decreased level of consciousness present or expected.
• Life expectancy less than 90 days.
• Follow-up in person or by telephone for 90 days is not feasible.
Sleep for Stroke Management and Recovery Trial (Sleep SMART)
The purpose of this study is to determine whether treatment of obstructive sleep apnea (OSA) with positive airway pressure starting shortly after acute ischemic stroke or high risk TIA (1) reduces recurrent stroke, acute coronary syndrome, and all-cause mortality 6 months after the event, and (2) improves stroke outcomes at 3 months in patients who experienced an ischemic stroke.
• TIA with ABCD2 ≥4 or ischemic stroke, within the prior 14 days.
• pre-event inability to perform all of own basic ADLs
• unable to obtain informed consent from subject or legally authorized representative
• known pregnancy
• current mechanical ventilation (can enroll later if this resolves) or tracheostomy
• current use of positive airway pressure, or use within one month prior to stroke
• anatomical or dermatologic anomaly that makes use of CPAP interface unfeasible
• severe bullous lung disease
• history of prior spontaneous pneumothorax or current pneumothorax
• hypotension requiring current treatment with pressors (can enroll later if this resolves)
• other specific medical circumstances that conceivably, in the opinion of the site PI, could render the patient at risk of harm from use of CPAP
• massive epistaxis or previous history of massive epistaxis
• cranial surgery or head trauma within the past 6 months, with known or possible CSF leak or pneumocephalus
• recent hemicraniectomy or suboccipital craniectomy (i.e. those whose bone has not yet been replaced), or any other recent bone removal procedure for relief of intracranial pressure
• current receipt of oxygen supplementation >4 liters per minute
• current contact, droplet, respiratory/airborne precautions
Management of the PDA Trial (PDA)
Estimate the risks and benefits of active treatment versus expectant management of a symptomatic patent ductus arteriosus (sPDA) in premature infants.
• Postnatal age 48 hours -21 days
• Infant 22 0/7 to 28 6/7 weeks gestation at birth
• sPDA, as defined as:
• Mild, Moderate, or Severe Clinical Criteria with Small or Moderate size PDA on echocardiogram
• Mild or Moderate Clinical Criteria with Large PDA on echocardiogram
• Cardiopulmonary compromise
• Known congenital heart disease (besides atrial septal defect or ventricular septal defect)
• Known pulmonary malformation (e.g. congenital lobar emphysema, congenital pulmonary adenomatous malformation)
• Any condition which, in the opinion of the investigator, would preclude enrollment
Mechanisms of Exercise Intolerance in Heart Failure With Preserved Ejection Fraction
The global objective of this study is to determine the mechanisms of exercise intolerance and dyspnea on exertion (DOE) in patients with HFpEF and based on this pathophysiology, test whether specific exercise training programs (whole body vs single leg) will result in improved exercise tolerance.
• signs and symptoms of heart failure
• an ejection fraction > 0.50
• objective evidence of diastolic dysfunction
• age < 60 years
• BMI > 50 kg/m2
• PDE5 inhibitor use
• Severe valvular disease
• Severe COPD
• CKD 4 or higher
• Contra-indication to MRI.
Hyperinflation Respiratory Therapies in Cardiac Surgery Patients
The purpose of this prospective randomized clinical trial is to evaluate three different types of hyperinflation respiratory therapies, Intermittent Positive Pressure Breathing (IPPB), Intermittent positive end expiratory pressure (EzPAP), Metaneb. Investigators will examine which hyperinflation therapy provides better lung expansion and may improve lung recovery after surgery.
• Age 18 years and older
• Admitted to Cardiovascular ICU (CVICU) after coronary artery bypass grafting (CABG), isolated valve repair/replacement, or CABG + valve repair/replacement
• Cardiac surgery performed via median sternotomy
• Refusal to be consented
• Prior or current lung transplant patients
CARDIO-TTRansform: A Study to Evaluate the Efficacy and Safety of Eplontersen (Formerly Known as ION-682884, IONIS-TTR-LRx and AKCEA-TTR-LRx) in Participants With Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM)
To evaluate the efficacy of eplontersen compared to placebo in participants with ATTR-CM receiving available standard of care (SoC). For more information, please visit https://www.cardio-ttransform.com.
• Females must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal or abstinent. If engaged in sexual relations of child-bearing potential, agree to use 1 highly effective contraceptive method
• Males must be surgically sterile or, abstinent or, if engaged in sexual relations with a woman of child-bearing potential, the participant or the participant's non-pregnant female partner must be using a highly effective contraceptive method
• Amyloid deposits in cardiac or non-cardiac tissue confirmed by Congo Red (or equivalent) staining OR technetium scintigraphy (99mTc -3,3-diphosphono-1,2- propanodicarboxylic acid [DPD-Tc], 99m Tc-pyrophosphate [PYP-Tc], or 99m Tc-hydroxymethylene-diphosphonate [HMDP-Tc]) with Grade 2 or 3 cardiac uptake in the absence of abnormal light chains ratio, centrally confirmed
• End-diastolic interventricular septum thickness of > 12 millimeters (mm) on Screening echocardiogram
• New York Heart Association (NYHA) class I-III
• Acute coronary syndrome, unstable angina, stroke, transient ischemic attack (TIA), coronary revascularization, cardiac device implantation, cardiac valve repair, or major surgery within 3 months of Screening
• Cardiomyopathy not primarily caused by ATTR-CM, for example, cardiomyopathy due to hypertension, valvular heart disease, or ischemic heart disease
• Monoclonal gammopathy of undetermined significance (MGUS) and/or alterations in immunoglobulin free light chain (FLC) ratio unless fat, bone marrow, or heart biopsy confirming the absence of light chain and the presence of TTR protein by mass spectrometry or immunoelectron microscopy. For participants with chronic kidney disease (CKD) and without presence of monoclonal protein in blood and urine, the acceptable FLC ratio is 0.26-2.25. Results different from that may be discussed with local hematologist, Investigator and Medical Monitor if the risks associated with the biopsy outweigh the benefits
• Prior liver or heart transplant, and/or Left Ventricular Assist Device (LVAD) or anticipated liver transplant or LVAD within 1 year after randomization
• Current or previous treatment with Tegsedi™ (inotersen) or Onpattro™ (patisiran) or other oligonucleotide or ribonucleic acid (RNA) therapeutic (including small interfering ribonucleic acid [siRNA]; does not apply to COVID-19 mitochondrial [mRNA] vaccinations)
• Current treatment with diflunisal, doxycycline, with or without ursodeoxycholic acid, and/or non-dihydropyridine calcium-channel blocker (e.g., verapamil, diltiazem). Participants receiving any of these agents must respect a wash-out period of 14 days before randomization.
Cardiovascular Responses to Heat Waves in the Elderly
The purpose of this study is to assess the cardiovascular responses of the elderly to heat wave conditions
• Healthy male and female individuals
• 18-35 years or 65+ years of age
• Free of any underlying moderate to serious medical conditions
• Known heart disease; other chronic medical conditions requiring regular medical therapy including cancer, diabetes, neurological diseases, uncontrolled hypertension, and uncontrolled hypercholesterolemia.
• Taking of any medications (such as beta blockers and non-dihydropyridine calcium channel blockers) that have known influences on either cardiac function or sweating responses.
• Abnormalities detected on routine screening.
• Individuals who participate in a structured aerobic exercise training program at moderate to high intensities.
• Current smokers, as well as individuals who regularly smoked within the past 3 years.
• Body mass index of greater than 30 kg/m^2
• Pregnant individuals
Pragmatic Evaluation of Events And Benefits of Lipid-lowering in Older Adults (PREVENTABLE)
PREVENTABLE is a multi-center, randomized, parallel group, placebo-controlled superiority study. Participants will be randomized 1:1 to atorvastatin 40 mg or placebo. This large study conducted in community-dwelling older adults without cardiovascular disease (CVD) or dementia will demonstrate the benefit of statins for reducing the primary composite of death, dementia, and persistent disability and secondary composites including mild cognitive impairment (MCI) and cardiovascular events.
• Community-dwelling adults
• Age ≥75 years
• English or Spanish as primary language
• Clinically evident cardiovascular disease defined as prior myocardial Infarction (MI), prior stroke, prior revascularization procedure, or a secondary prevention indication for a statin (clinician determined)
• Hospitalization for a primary diagnosis of heart failure in the prior 12 months (Note: History of heart failure in the absence of recent hospitalization or clinically evident cardiovascular disease is not an exclusion)
• Dementia (clinically evident or previously diagnosed)
• Dependence in any Katz Basic Activities of Daily Living [ADL] (with the exception of urinary or bowel continence)
• Severe hearing impairment (preventing phone follow up)
• Unable to talk (preventing phone follow up)
• Severe visual impairment (preventing cognitive testing)
• Statin use in the past year or for longer than 5 years previously (participant reported)
• Ineligible to take atorvastatin 40 mg (clinician determined)
• Documented intolerance to statins
• Active Liver Disease
• Long-term use of daily colchicine, verapamil at any dose, or diltiazem at a dose >240mg/day.
A Phase 3 Trial of Pamrevlumab or Placebo in Combination With Systemic Corticosteroids, in Subjects With Non-ambulatory Duchenne Muscular Dystrophy (DMD)
To evaluate the efficacy and safety of pamrevlumab versus placebo in combination with systemic corticosteroids in subjects with non-ambulatory Duchenne muscular dystrophy (age 12 years and older).
• Males at least 12 years of age, non-ambulatory at screening initiation
• Written consent by patient and/or legal guardian as per regional/ country and/or IRB/IEC requirements
• Male subjects with partners of childbearing potential must use contraception during the conduct of the study, and for 3 months after the last dose of study drug.
• Medical history includes diagnosis of DMD and confirmed Duchenne mutation using a validated genetic test
• Brooke Score for Arms and Shoulders ≤5
• Able to undergo MRI test for the upper arm extremities (Biceps Brachii muscle) and cardiac muscle
• Able to perform spirometry
• Average (of Screening and Day 0) percent predicted FVC between 45 and 85, inclusive
• Left ventricular ejection fraction ≥50% as determined by cardiac MRI at screening or within 3 months prior to randomization (Day 0)
• Prior diagnosis of cardiomyopathy, subjects must be on a stable regimen dose for cardiomyopathy/ heart failure medications (e.g., angiotensin converting enzyme inhibitors, aldosterone receptors blockers, angiotensin-receptor blockers, and betablockers) for at least 1 month prior to screening
• On a stable dose of systemic corticosteroids for a minimum of 6 months, with no substantial change in dosage for a minimum of 3 months (except for adjustments for changes in body weight) prior to screening. Corticosteroid dosage should be in compliance with the DMD Care Considerations Working Group recommendations (e.g.prednisone or prednisolone 0.75 mg/kg per day or deflazacort 0.9 mg/kg per day) or stable dose. A reasonable expectation is that dosage and dosing regimen would not change significantly for the duration of the study.
• Received pneumococcal vaccine (PPSV23) (or any other pneumococcal polysaccharide vaccine as per national recommendations) and is receiving annual influenza vaccinations
• Adequate renal function: cystatin C ≤1.4 mg/L
• Adequate hematology and electrolytes parameters:
• Platelets >100,000/mcL
• Hemoglobin >12 g/dL
• Absolute neutrophil count >1500 /μL
• Serum calcium (Ca), potassium (K), sodium (Na), magnesium (Mg) and phosphorus (P) levels are within a clinically accepted range
• Adequate hepatic function:
• No history or evidence of liver disease
• Gamma glutamyl transferase (GGT) ≤3x upper limit of normal (ULN)
• Total bilirubin ≤1.5xULN
• Previous exposure to pamrevlumab
• BMI ≥40 kg/m2 or weight >117 kg
• History of allergic or anaphylactic reaction to human, humanized, chimeric or murine monoclonal antibodies
• Exposure to any investigational drug (for DMD or not), in the 30 days prior to screening initiation or use of approved DMD therapies (e.g., eteplirsen, ataluren, golodirsen) within 5 half-lives of screening, whichever is longer, with the exception of the systemic corticosteroids, including deflazacort
• Severe uncontrolled heart failure (NYHA Classes III-IV), including any of the following:
• Need for intravenous diuretics or inotropic support within 8 weeks prior to screening
• Hospitalization for a heart failure exacerbation or arrhythmia within 8 weeks prior to screening
• Arrhythmia requiring anti-arrhythmic therapy
• Requires ≥16 hours continuous ventilation
• Hospitalization due to respiratory failure within the 8 weeks prior to screening
• Poorly controlled asthma or underlying lung disease such as bronchitis, bronchiectasis,emphysema, recurrent pneumonia that in the opinion of the investigator might impact respiratory function
• The Investigator judges that the subject will be unable to fully participate in the study and complete it for any reason, including inability to comply with study procedures and treatment, or any other relevant medical or psychiatric conditions
Polypill Strategy for Heart Failure With Reduced Ejection Fraction
Heart failure with a reduced ejection fraction (HFrEF) represents a significant public health burden in the United States, with a growing prevalence particularly among African Americans and Hispanic Americans and individuals of low socioeconomic status (SES). Although effective therapies exist, gaps in their uptake contribute substantially to the excess burden of heart failure. The "polypill" is an inexpensive once daily pill containing three agents proven to improve morbidity and mortality in heart failure and represents potential strategy for increasing the utilization of proven HF therapies. The proposed study is a pragmatic, single-center, randomized trial to test the feasibility and effectiveness of a polypill-based strategy for the treatment of HFrEF in a low-income, racially diverse population.
• Adults age > = 18 years
• HF with left ventricular ejection fraction <= 40% within 3 months of screening who are not on optimal guideline directed medical therapy
• New York Heart Association class II, III, or IV symptoms
• Age < 18
• Systolic blood pressure < 120 mm Hg at enrollment
• Estimated glomerular filtration rate < 30 mL/min/1.73 m2 as measured by the simplified
• MDRD formula
• Serum potassium > 5.0 mEq/L
• Current need for inotropes
• Cardiac index < 2.2 L/min/m2
• History of revascularization within 30 days or plan for revascularization
• History of type 1 diabetes mellitus
• History of allergic reaction or contraindication to a beta-blocker (BB), mineralocorticoid receptor antagonist (MRA), or sodium glucose cotransporter 2 inhibitor (SGLT2i)
• Contraindication to receive any of the components of the polypill
• < 12 month expected survival
• Inability to provide written informed consent
• Persistent or permanent atrial fibrillation who may not have optimal MRI imaging
• Extreme obesity (BMI > 45 kg/m2)
• ICD/PAcemaker devices that are incompatible with MRI
Innovative Support for Patients With SARS-COV2 Infections (COVID-19) Registry (INSPIRE) (INSPIRE)
The Innovative Support for Patients with SARS COV-2 Infections Registry (INSPIRE) study is a CDC-funded COVID-19 project to understand the long-term health outcomes in recently tested adults, both negative and positive, who have suspected COVID symptoms at the time of their test. Participants will complete short online surveys every 3 months for 18 months, share information about their health using a secure web-based platform, and are compensated for their time.
• Fluent in English or Spanish;
• Age 18 and over;
• Self-reported symptoms suggestive of acute SARSCOV2 infection;
• Under investigation for SARSCOV2 (defined as a patient who has received any screening or diagnostic test used to detect the presence of COVID19 including any FDA approved or authorized molecular or antigen-based assay) within the last 42 days. EXCLUSION CRITERIA
• Unable to provide informed consent;
• Study team unable to confirm result of diagnostic test for SARSCOV2;
• Does not have access to a hand-held device or computer that would allow for digital participation in the study;
• Individuals who are prisoners while participating in the study.
A 12 Month Site Randomized Trial in Adults With Type 2 Diabetes Mellitus and History of Cardiovascular Disease (COORDINATE)
COORDINATE-Diabetes is a cluster-randomized clinical trial to test the effectiveness of an innovative, clinic-level educational intervention to improve the management of patients with type 2 diabetes mellitus and cardiovascular disease.
• Age ≥ 18 years old
• Diagnosis of Type 2 diabetes mellitus (T2DM)
• History of at least one of the following conditions:
• Coronary artery disease (defined as prior MI, coronary revascularization (CABG or PCI), and/or obstructive CAD (≥50%) as documented by angiography or CTA)
• Stroke and/or carotid artery stenosis (≥50%)
• Peripheral Arterial disease (defined as claudication with ABI<0.9, prior peripheral revascularization, and/or amputation due to circulatory insufficiency)
• Ability to communicate with site staff and understand and provide written informed consent and proof of Health Insurance Portability and Accountability Act (HIPAA) authorization
• Determined to be highly unlikely to survive and/or to continue follow-up in that clinic for at least 1 year, as identified by site investigator
• GFR<30 mL/min/1.73m2
• Already on all guideline-recommended therapies for T2DM and CVD
• Absolute contraindication to any of the guideline recommended therapies for T2DM and CVD