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15 Study Matches
Negative Pressure Wound Therapy in Cesarean Section (NPWTCS)
The investigators propose a prospective, randomized trial evaluating the use of negative pressure wound therapy (NPWT) with high risk obstetrical patients. The investigators hypothesize that negative pressure wound therapy will decrease the wound complications in these patients. The investigators aim to look at all wound complications such as infection and disruption and will be using Prevena incision management system for our NPWT device .
10 Years to 64 Years old
• Pregnant women with BMI > 40 undergoing a cesarean delivery at Parkland Health and Hospital System.
• Any patient not meeting inclusion criteria will be deemed ineligible.
• All HIV positive patients will be excluded due to the increased risk of infectious complications in these patients.
• Although patients on anticoagulants can use NPWT, they will be excluded as there may be an increased risk of bleeding in these patients.
• according to the wound therapy manufacturer's instructions patients with:
• fragile skin
• allergy to silver or acrylic adhesives
• a malignancy in the wound bed or margins of the wound bed
• non-enteric and unexplored fistulas
• necrotic tissue with eschar present
• exposed arteries, veins, nerves or organs, anastomotic sites, or surgical suction are not candidates for usage of the device.
Device: Negative pressure wound therapy
Postoperative Wound Complications
Efficacy and Safety Study of Maribavir Treatment Compared to Investigator-assigned Treatment in Transplant Recipients With Cytomegalovirus (CMV) Infections That Are Refractory or Resistant to Treatment With Ganciclovir, Valganciclovir, Foscarnet, or Cidofovir
Ricardo La Hoz
12 Years and over
Inclusion Criteria:1. The participant must be able to provide written, personally signed, and dated informed consent to participate in the study before completing any study-related procedures. As applicable, a parent/both parents or legally authorized representative (LAR) must provide signature of informed consent and there must be documentation of assent by the participant before completing any study-related procedures. 2. The participant must be a recipient of hematopoietic stem cell or solid organ transplant. 3. The participant must have a documented CMV infection in whole blood or plasma, with a screening value of greater than or equal to (>=) 2730 international units per milliliter (IU/mL) in whole blood or >= 910 IU/mL in plasma in 2 consecutive assessments, separated by at least 1 day, as determined by local or central specialty laboratory quantitative polymerase chain reaction (qPCR) or comparable quantitative CMV DNA results. Both samples should be taken within 14 days prior to randomization with second sample obtained within 5 days prior to randomization. The same laboratory and same sample type (whole blood or plasma) must be used for these assessments. 4. The participant must have a current CMV infection that is refractory to the most recently administered of the four anti-CMV treatment agents. Refractory is defined as documented failure to achieve greater than (>) 1 log10 (common logarithm to base 10) decrease in CMV DNA level in whole blood or plasma after a 14 day or longer treatment period with intravenous (IV) ganciclovir/oral valganciclovir, IV foscarnet, or IV cidofovir. a. Participants with documentation of 1 or more CMV genetic mutations associated with resistance to ganciclovir/valganciclovir, foscarnet, and/or cidofovir must also meet the definition of refractory CMV infection. 5. The Investigator must be willing to treat the participant with at least one of the available anti-CMV drugs (ganciclovir, valganciclovir, foscarnet, or cidofovir). Note: Combination therapy with foscarnet and cidofovir is not permitted in the investigator-assigned anti-CMV treatment (IAT) arm due to the potential for serious nephrotoxicity. 6. The participant must be >= 12 years of age at the time of consent. 7. The participant must weigh >= 35 kilogram (kg). 8. The participant must have all of the following results as part of screening laboratory assessments (results from either the central laboratory or a local laboratory can be used for qualification): 1. Absolute neutrophil count (ANC) >= 1000/ millimeter cube (mm^3) (1.0 x 10^9/liter [L]) 2. Platelet count >= 25,000/mm^3 [25 x 10^9/L], 3. Hemoglobin >= 8 grams per deciliter (g/dL). 4. Estimated glomerular filtration rate (eGFR) > 30 (milliliters per minute (mL/min) /1.73 square meter (m^2) as assessed by Modification of Diet in Renal Disease (MDRD) formula for participants >= 18 years of age or Schwartz formula for participants less than (<) 18 years of age. 9. The participant must have a negative serum beta-human chorionic gonadotropin (beta-HCG) pregnancy test at screening, if a female of child bearing potential. Additional urine pregnancy tests may be done per institutional requirements. Sexually active females of child bearing potential must agree to comply with any applicable contraceptive requirements of the protocol. If male, must agree to use an acceptable method of birth control, as defined in the protocol, during the study treatment administration period and for 90 days afterward if treated with maribavir, ganciclovir, valganciclovir, or cidofovir and for 180 days afterward if treated with foscarnet. 10. The participant must be able to swallow tablets, or receive tablets crushed and/or dispensed in water via nasogastric or orogastric tube. 11. The participant must be willing and have an understanding and ability to fully comply with study procedures and restrictions defined in the protocol. 12. The participant must be willing to provide necessary samples (example [e.g,] biopsy) for the diagnosis of tissue invasive CMV disease at baseline as determined by the Investigator. 13. The participant must have a life expectancy of >= 8 weeks.
Exclusion Criteria:1. Have a current CMV infection that is considered refractory or resistant due to inadequate adherence to prior anti-CMV treatment, to the best knowledge of the Investigator. 2. Require ganciclovir, valganciclovir, foscarnet, or cidofovir administration for conditions other than CMV when study treatment is initiated (example: herpes simplex virus (HSV) coinfection requiring use of any of these agents after the randomization) or would need a coadministration with maribavir for CMV infection. NOTE: A participant who is not continuing with the same anti-CMV drug(s) (ganciclovir, valganciclovir or foscarnet) for the study treatment (if randomized to the investigator assigned anti-CMV treatment arm), must discontinue their use before the first dose of study drug. If participant is currently being treated with cidofovir and is assigned another anti-CMV therapy by the investigator, the participant must discontinue its use at least 14 days prior to randomization at Visit 2/Day 0 and the first dose of study treatment. 3. Be receiving leflunomide, letermovir, or artesunate when study treatment is initiated. NOTE: Participants receiving leflunomide must discontinue the use at least 14 days prior to randomization at Visit 2/Day 0 and the first dose of study treatment. Participants receiving letermovir must discontinue use at least 3 days prior to the first dose of study treatment. Participants receiving artesunate must discontinue the use prior to the first dose of study treatment. 4. Have severe vomiting, diarrhea, or other severe gastrointestinal illness within 24 hours prior to the first dose of study treatment that would preclude administration of oral/enteral medication. 5. Have known hypersensitivity to the active substance or to an excipient for a study treatment. 6. Have tissue invasive CMV disease with central nervous system involvement including the retina (example, CMV retinitis). 7. Have serum aspartate aminotransferase (AST) > 5 times upper limit of normal (ULN) at screening, or serum alanine aminotransferase (ALT) > 5 times ULN at screening, or total bilirubin >= 3.0 x ULN at screening (except for documented Gilbert's syndrome), by local or central lab. Participants with biopsy confirmed CMV hepatitis will not be excluded from study participation despite AST or ALT > 5 times ULN at screening. 8. Have known positive results for human immunodeficiency virus (HIV). Participants must have a confirmed negative HIV test result within 3 months of study entry or, if unavailable, be tested by a local laboratory during the screening period. 9. Require mechanical ventilation or vasopressors for hemodynamic support at the time of enrollment. 10. Be female and pregnant or breast feeding. 11. Have previously received maribavir. 12. Have received any investigational agent with known anti-CMV activity within 30 days before initiation of study treatment or investigational CMV vaccine at any time. 13. Have received any unapproved agent or device within 30 days before initiation of study treatment. 14. Have active malignancy with the exception of nonmelanoma skin cancer. Participants who have had a hematopoietic stem cell transplant (HSCT) and who experience relapse or progression of the malignancy as per investigator's opinion are not to be enrolled. 15. Be undergoing treatment for acute or chronic hepatitis C. 16. Have any clinically significant medical or surgical condition that, in the investigator's opinion, could interfere with the interpretation of study results, contraindicate the administration of the assigned study treatment, or compromise the safety or well-being of the participant.
Drug: Maribavir, Drug: Ganciclovir, Drug: Valganciclovir, Drug: Foscarnet, Drug: Cidofovir
Individualized Treatment in Treating Patients With Stage II-IVB Nasopharyngeal Cancer Based on EBV DNA
There are two study questions we are asking in this randomized phase II/III trial based on a blood biomarker, Epstein Barr virus (EBV) deoxyribonucleic acid (DNA) for locoregionally advanced non-metastatic nasopharyngeal cancer. All patients will first undergo standard concurrent chemotherapy and radiation therapy. When this standard treatment is completed, if there is no detectable EBV DNA in their plasma, then patients are randomized to either standard adjuvant cisplatin and fluorouracil chemotherapy or observation. If there is still detectable levels of plasma EBV DNA, patients will be randomized to standard cisplatin and fluorouracil chemotherapy versus gemcitabine and paclitaxel. Radiation therapy uses high energy x rays to kill tumor cells. Drugs used in chemotherapy, such as cisplatin, fluorouracil, gemcitabine hydrochloride, and paclitaxel work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving cisplatin and fluorouracil is more effective than gemcitabine hydrochloride and paclitaxel after radiation therapy in treating patients with nasopharyngeal cancer.
18 Years and over
Phase 2/Phase 3
• Biopsy proven (from primary lesion and/or lymph nodes) diagnosis of cancer of the nasopharynx
• Patients must have detectable pretreatment plasma EBV DNA, determined by the central lab prior to Step 2 registration
• Stage II-IVB disease (American Joint Committee on Cancer [AJCC], 7th edition [ed.]) with no evidence of distant metastasis, based upon the following minimum diagnostic workup:
• History/physical examination by a Medical Oncologist or Clinical Oncologist or Radiation Oncologist or Ear, Nose, Throat specialist (ENT), which must include an endoscopic evaluation, a complete list of current medications, and assessment of weight and weight loss in the past 6 months within 21 days prior to registration
• Evaluation of tumor extent with magnetic resonance imaging (MRI) of the nasopharynx and neck within 28 days prior to registration; if MRI is medically contraindicated, obtain computed tomography (CT) scan with =< 3 mm contiguous slices with contrast and bone windows (to evaluate base of skull involvement); Note: If a treatment planning CT scan is used, it must be with =< 3 mm contiguous slices with contrast and be read by a radiologist
• To rule out distant metastasis, patients must undergo the following imaging within 28 days prior to registration:
• A CT scan with contrast of the chest, abdomen, and/or pelvis or a total body positron emission tomography (PET)/CT scan (non-contrast PET/CT is acceptable)
• A bone scan only when there is suspicion of bone metastases (a PET/CT scan can substitute for the bone scan)
• Zubrod performance status 0-1 within 21 days prior to registration
• Absolute neutrophil count (ANC) >= 1,500 cells/mm^3
• Platelets >= 100,000 cells/mm^3
• Hemoglobin >= 8.0 g/dl (Note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dl is acceptable)
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 1.5 x institutional ULN
• Alkaline phosphatase =< 1.5 x institutional ULN
• Serum creatinine =< 1.5 mg/dl or calculated creatinine clearance (CC) >= 50 ml/min determined by 24-hour urine collection or estimated by Cockcroft-Gault formula
• Negative serum pregnancy test within 14 days prior to registration for women of childbearing potential
• Women of childbearing potential and male participants who are sexually active must agree to use a medically effective means of birth control throughout protocol treatment
• Patient must provide study specific informed consent prior to study entry, including the mandatory pre-treatment plasma EBV DNA assay
• Prior invasive malignancy (except node negative, non-melanomatous skin cancer) unless disease free for a minimum of 1095 days (3 years) (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible)
• Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable; however, at least 6-weeks recovery is necessary if the last regimen included nitrosourea or mitomycin
• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
• Patients with hearing loss assessed to be primarily sensorineural in nature, requiring a hearing aid, or intervention (i.e. interfering in a clinically significant way with activities of daily living); a conductive hearing loss that is tumor-related is allowed
• >= Grade 2 peripheral sensory neuropathy (CTCAE, v. 4.0)
• Severe, active co-morbidity, defined as follows:
• Major medical or psychiatric illness, which in the investigator's opinion would interfere with the completion of therapy and follow up or with full understanding of the risks and potential complications of the therapy
• Unstable angina and/or uncontrolled congestive heart failure within the past 6 months
• Myocardial infarction within the last 6 months
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration; note that patients switched from IV antibiotics and currently on oral antibiotics whose infection is assessed to be adequately treated or controlled are eligible
• Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days prior to registration
• Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol
• Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
• Prior allergic reaction to the study drug(s) involved in this protocol
• Patients with undetectable pre-treatment plasma EBV DNA
Drug: Cisplatin, Other: Clinical Observation, Drug: Fluorouracil, Drug: Gemcitabine Hydrochloride, Radiation: Intensity-Modulated Radiation Therapy, Other: Laboratory Biomarker Analysis, Drug: Paclitaxel, Other: Quality-of-Life Assessment
Epstein-Barr Virus Infection, Stage II Nasopharyngeal Carcinoma, Stage III Nasopharyngeal Carcinoma, Stage IVA Nasopharyngeal Carcinoma, Stage IVB Nasopharyngeal Carcinoma
A Study of AeroVanc for the Treatment of MRSA Infection in CF Patients
6 Years and over
Inclusion Criteria 1. Subjects ≥ 6 years of age at time of Informed Consent Form (ICF) or Assent Form signing. 2. Confirmed diagnosis of CF, determined by having clinical features consistent with the CF phenotype, plus one of the following: 1. Positive sweat chloride test (value ≥ 60 mEq/L), 2. Genotype with 2 mutations consistent with CF (i.e., a mutation in each of the cystic fibrosis transmembrane conductance regulator [CFTR] genes). 3. Positive sputum culture or a throat swab culture for MRSA at Screening. 4. In addition to the Screening sample, have at least 2 prior sputum or throat swab cultures positive for MRSA, of which at least 1 sample is more than 6 months prior to Screening. At least 50% of all MRSA cultures (sputum or throat swab culture) collected from the time of the first positive culture (in the previous 1 year) must have tested positive for MRSA. (Note: Screening sample may count towards 50% positive count) 5. Forced expiratory volume in 1 second (FEV1) ≥ 30% and ≤ 90% of predicted that is normal for age, gender, race, and height, using the Global Lung Function Initiative (GLI) equation. 6. At least 1 episode of acute pulmonary infection treated with non-maintenance antibiotics within 12 months prior to the Baseline visit. (Initiation of treatment with intermittent inhaled anti-Pseudomonal therapy will not qualify as treatment with non-maintenance antibiotics). 7. If female of childbearing potential, an acceptable method of contraception must be used during the study and must be combined with a negative pregnancy test obtained during Screening; sexually active male subjects of reproductive potential who are non-sterile (i.e., male who has not been sterilized by vasectomy for at least 6 months, and were not diagnosed with infertility through demonstration of azoospermia in a semen sample and/or absence of vas deferens through ultrasound) must be willing to use a barrier method of contraception, or their female partner must use an acceptable method of contraception, during the study. For purposes of this study, the Sponsor defines "acceptable methods of contraception" as: 1. Oral birth control pills administered for at least 1 monthly cycle prior to administration of the study drug. 2. A synthetic progestin implanted rod (eg, Implanon®) for at least 1 monthly cycle prior to the study drug administration but not beyond the 4th successive year following insertion. 3. Intrauterine devices (IUDs), inserted by a qualified clinician for at least 1 monthly cycle prior to study drug administration. 4. Medroxyprogesterone acetate (eg, Depo-Provera®) administered for a minimum of 1 monthly cycle prior to administration of the study drug and continuing through 1 month following study completion. 5. Hysterectomy or surgical sterilization. 6. Abstinence. 7. Double barrier method (diaphragm with spermicidal gel or condoms with contraceptive foam). NOTE: For subjects prescribed Orkambi: Orkambi may substantially decrease hormonal contraceptive exposure, reducing the effectiveness and increasing the incidence of menstruation-associated adverse reactions. Hormonal contraceptives, including oral, injectable, transdermal, and implantable, should not be relied upon as an effective method of contraception when co-administered with Orkambi. 8. Able and willing to comply with the protocol, including availability for all scheduled study visits and able to perform all techniques necessary to use the AeroVanc inhaler and measure lung function. 9. Agree not to smoke during any part of the clinical trial (Screening visit through end of study). 10. Subjects with a P. aeruginosa co-infection must either be stable on a regular suppression regimen of inhaled antibiotics or must be, in the opinion of the Investigator, stable despite the lack of such treatment. Exclusion Criteria 1. Use of anti-MRSA treatments prescribed as maintenance therapy (intravenous [IV] or inhaled treatment within 28 days; oral treatment within 14 days) prior to the Baseline visit. 2. Use of non-maintenance antibiotic for pulmonary infection or extrapulmonary MRSA infection (IV or inhaled antibiotic within 28 days; oral antibiotic within 14 days) prior to the Baseline visit. 3. History of previous allergies or sensitivity to vancomycin, or other component(s) of the study drug or placebo except for a history of red-man syndrome. 4. Inability to tolerate inhaled products. 5. First time sputum culture or throat swab culture yielding B. cepacia, or nontuberculous Mycobacteria in the previous 6 months to Screening. 6. History of lung or other solid organ transplantation or currently on the list to receive lung or other solid organ transplantation. 7. Resistance to vancomycin at Screening (vancomycin resistant Staphylococcus aureus [VRSA], or vancomycin intermediate resistant Staphylococcus aureus [VISA], with minimum inhibitory concentration [MIC] ≥ 8 μg/mL). 8. Oral corticosteroids in doses exceeding 10 mg prednisone per day or 20 mg prednisone every other day, or equipotent doses of other corticosteroids. 9. Changes in antimicrobial, bronchodilator, anti-inflammatory or corticosteroid medications within 14 days, or changes in CFTR modulators within 28 days, prior to the Baseline visit. 10. Abnormal laboratory findings or other findings or medical history at Screening that, in the Investigator's opinion, would compromise the safety of the subject or the quality of the study data. 11. Inability to tolerate inhalation of a short acting beta2 agonist 12. SpO2 <90% at Screening. 13. Changes in physiotherapy technique or physiotherapy scheduled within 1 week of the Baseline visit. 14. Administration of any investigational drug or device within 4 weeks prior to the Screening visit and during the study 15. Female with positive pregnancy test result during Screening, pregnant (or intends to become pregnant), lactating or intends to breastfeed during the study. 16. Renal insufficiency, defined as creatinine clearance < 50 mL/min using the Cockcroft-Gault equation for adults or Schwartz equation for children at the Screening visit. 17. Abnormal liver function, defined as ≥ 4x upper limit of normal (ULN), of serum aspartate aminotransferase (AST) or serum alanine aminotransferase (ALT), or known cirrhosis at Screening. 18. Diagnosed with clinically significant hearing loss. 19. History of positive result for human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). 20. Planned hospitalizations for prophylaxis antibiotic treatment within 28 days prior to Baseline visit or during the double-blind period (Period 1).
Drug: Vancomycin inhalation powder, Drug: Placebo inhalation powder
Cystic Fibrosis, MRSA
Local Antibiotic Therapy to Reduce Infection After Operative Treatment of Fractures at High Risk of Infection: A Multicenter Randomized, Controlled Trial (VANCO) (VANCO)
The Vancomycin Study is a multi-center, prospective randomized controlled trial that will compare the proportion of deep surgical site infections within 6 months in patients treated with local Vancomycin powder compared to those treated without local Vancomycin powder at the time of fracture fixation.
18 Years to 80 Years old
• All "high energy" tibial plateau fractures treated operatively with plate and screw fixation.
• We define "high energy" tibial plateau fractures as patients who are either:
• Initially treated with an external fixation (with or without limited internal fixation) and treated definitively more than 3 days later after swelling has resolved.
• Any open type I, II, or IIIA fracture, regardless of timing of definitive treatment.
• Any tibial plateau fracture associated with ipsilateral leg compartment syndrome fasciotomy wounds.
• All "high energy" pilon (distal tibial plafond) fractures treated operatively with plate and screw fixation. We define "high energy" pilon fractures as patients who are either:
• Initially treated with an external fixation (with or without fibula fixation or limited internal fixation) and treated definitively more than 3 days later after swelling has resolved.
• Any open type I, II, or IIIA fracture, regardless of timing of definitive treatment.
• Any tibial pilon fracture associated with ipsilateral leg compartment syndrome fasciotomy wounds.
• Ages 18 to 80 years
• Patients may have co-existing non-tibial infection, with or without antibiotic treatment.
• Patients may have risk factors for infection including diabetes, immunosuppression from steroids or other medications, HIV, or other infections.
• Patients may have a head injury
• Patients may have a portion of the fixation (e.g. fibula fixation in pilon or percutaneous screws across a tibial plateau fracture) prior to definitive plate fixation, at the initial surgery before randomization.
• Patients may have other orthopedic and non-orthopaedic injuries.
• Patients may have pre-existing musculoskeletal injuries, be non ambulators, or have spinal cord injuries.
• Women and minorities are included
• The study injury: tibial plateau, pilon, is already infected at time of study enrollment.
• Patient speaks neither English nor Spanish.
• Patients who have already had definitive fixation prior to enrollment in the study.
• Severe problems with maintaining follow-up (e.g. patients who are homeless at the time of injury or those how are intellectually challenged without adequate family support).
• Patients with allergies, drug administration reactions, or other sensitivities to Vancomycin (such as a history of Redman's Syndrome).
• The study injury is a type IIIB or IIIC open fracture.
Drug: Vancomycin antibiotic powder
Post Operative Surgical Site Infection
Surgical site infection risk prevention, Bacterial species type and antibacterial sensitives
Rituximab and LMP-Specific T-Cells in Treating Pediatric Solid Organ Recipients With EBV-Positive, CD20-Positive Post-Transplant Lymphoproliferative Disorder
up to 29 Years old
• Patient must have a history of solid organ transplantation
• Patients must have biopsy-proven newly diagnosed polymorphic or monomorphic PTLD using the World Health Organization (WHO) classification and that is:
• CD20 positive
• EBV positive by Epstein-Barr virus early ribonucleic acid (RNA) (EBER) in situ hybridization (preferred) and/or LMP immunoperoxidase staining
• There must be measurable disease at study entry
• Note: a measurable node must have an LDi (longest diameter) greater than 1.5 cm; a measurable extranodal lesion should have an LDi greater than 1.0 cm; all tumor measurements must be recorded in millimeters (or decimal fractions of centimeters)
• Patients must be considered medically refractory to decreased immunosuppression (50% or greater reduction) for at least 1 week or there must be documentation in the medical chart that decreased immunosuppression would be associated with an unacceptable risk of rejection
• Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0 or 1
• Use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
• Patients must have a life expectancy of >= 8 weeks
• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
• Myelosuppressive chemotherapy: must not have received within 2 weeks of entry onto this study
• Must not have received therapy with anti-CD20 monoclonal antibodies within 90 days of entry onto this study
• Must not have received any prior radiation to any sites of measurable disease
• Must not have received any prior stem cell transplant
• Must not have received investigational therapy within 30 days of entry onto this study
• Must not have received prior EBV or LMP-specific T cells within 90 days of entry onto this study
• Must not have received alemtuzumab or other anti-T-cell antibody therapy within 28 days of entry onto this study
• Burkitt morphology
• Central nervous system (CNS) involvement; CNS status must be confirmed by lumbar puncture
• Note: lumbar puncture can be performed at the time of diagnosis and does not need to be repeated unless there is a change in neurological status or it was performed more than 14 days prior to study entry
• Bone marrow involvement (> 25%)
• Note: bone marrow aspiration/biopsy can be performed at the time of diagnosis and does not need to be repeated unless there is a change in peripheral blood counts or it was performed more than 14 days prior to study entry
• Fulminant PTLD defined as: fever > 38 degrees Celsius (C), hypotension, and evidence of multi-organ involvement/failure including two or more of the following:
• Bone marrow (including pancytopenia without any detectable B-cell proliferation)
• Liver (coagulopathy, transaminitis and/or hyperbilirubinemia)
• Lungs (interstitial pneumonitis with or without pleural effusions)
• Gastrointestinal hemorrhage
• Any documented donor-derived PTLD
• Hepatitis B or C serologies consistent with past or current infections
• Severe and/or symptomatic refractory concurrent infection other than EBV
• Pregnant females are ineligible
• Lactating females are not eligible unless they have agreed not to breastfeed their infants
• Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
• Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation and until six months after completion of study therapy
• All patients and/or their parents or legal guardians must sign a written informed consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Biological: Allogeneic LMP1/LMP2-Specific Cytotoxic T-Lymphocytes, Other: Laboratory Biomarker Analysis, Biological: Rituximab
CD20 Positive, EBV-Related Post-Transplant Lymphoproliferative Disorder, Epstein-Barr Virus Positive, Monomorphic Post-Transplant Lymphoproliferative Disorder, Polymorphic Post-Transplant Lymphoproliferative Disorder, Solid Organ Transplantation Recipient
Safety of 1 g and 2 g of Cefazolin in Pediatric Subjects
10 Years to 17 Years old
Inclusion Criteria:1. The subject is between the ages of 10 and 17 years (inclusive) at the time of giving informed consent. 2. The subject is scheduled for surgery that will last less than 3 hours. 3. The subject and the subject's legally authorized representative voluntarily agree that the subject will participate in this study. In accordance with applicable laws, regulations, and institutional review board requirements, the subject signs or orally agrees to an age-appropriate assent and the subject's legally authorized representative signs both an institutional review board approved informed consent form and Health Insurance Portability and Accountability Act authorization prior to the performance of any screening procedures. 4. For subjects who agree to participate in the PK subgroup additional consent will be obtained. 5. The subject weighs (on Day 1) ≥25 kg but <60 kg for inclusion in 1 g dose group. 6. The subject weighs (on Day 1) ≥60 kg for inclusion in 2 g dose group. 7. The subject has been scheduled for any type of surgery requiring single dose perioperative cefazolin prophylaxis.
Exclusion Criteria:1. Female subjects who are pregnant or lactating/breastfeeding. 2. Female subjects of childbearing potential who are sexually active and who are not willing to use an effective method of birth control during the study period, eg, oral contraceptives, double barrier methods, hormonal injectable or implanted contraceptives, tubal ligation, or have a partner with a vasectomy. 3. The subject has impaired renal function based on the revised Schwartz formula. 4. The subject has a known allergy or hypersensitivity to β lactam/cephalosporin antibiotics, penicillins, corn products, or dextrose containing products or solutions, or any of the other ingredients of Cefazolin for Injection United States Pharmacopeia (USP) and Dextrose Injection USP in DUPLEX. 5. The subject has abnormal vital signs or an abnormal electrocardiograph (ECG) considered by the investigator to be clinically significant. 6. The subject has a result of any laboratory test (or repeat test, if done), obtained as standard of care, that is outside the normal limit of the site's laboratory reference range AND is considered by the investigator to be clinically significant. 7. The subject has a known history of human immunodeficiency virus, hepatitis B, or hepatitis C infection. 8. The subject has a history of alcohol or drug abuse. 9. The subject has received any other investigational drug/device within 30 days prior to the study drug administration. 10. The subject has a history of or is currently smoking or using nicotine-containing substances or electronic cigarettes as determined by medical history or subject's verbal report.
Drug: Cefazolin 1 g Infusion, Drug: Cefazolin 2 g Infusion
EC-18 for Oral Mucositis in Patients With Concomitant Chemoirradiation
18 Years and over
• Signed informed consent
• Male or female age 18 years or older
• Pathologically confirmed diagnosis of squamous cell carcinoma of the mouth, oropharynx, hypopharynx or nasopharynx
• Planned to receive IMRT with daily fractions of 2.0 Gy to 2.2 Gy to a cumulative dose of at least 60 Gy and a maximum of 72 Gy
• Radiation fields to include at least two mucositis sites at risk (buccal mucosa, floor of mouth, ventral and lateral tongue, soft palate) in which both sites receive a minimum cumulative dose of 55 Gy
• Planned to receive concomitant single agent chemotherapy with cisplatin given either weekly or tri-weekly
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1
• Screening Laboratory Values Hemoglobin ≥ 9g/dL White blood cell count ≥ 3,500 cells/mm3 Absolute neutrophil count ≥ 1,500 cells/mm3 Total bilirubin ≤ 2 times upper limit of normal Serum AST and ALT ≤ 2.5 times upper limit of normal Serum creatinine concentration ≤ 2mg/mL Pregnancy test: negative for females of childbearing potential
• Subjects of childbearing potential must consent to utilize a medically accepted means of contraception throughout the active dosing period with study medication and for a minimum of 30 days following the administration of the last dose of study medication.
• Unable to provide informed consent or, in the opinion of the Principal Investigator, comply with the protocol.
• Prior radiation therapy to the head and neck
• Metastatic disease
• Presence of active infectious disease excluding oral candidiasis
• Presence of oral mucositis or any oral lesion that would confound the assessment of oral mucositis
• Active systemic disease or condition known to impact the risk or course of oral mucositis including chronic immunosuppression and known seropositivity for HIV
• Use of any investigational agent within 30 days of the first radiation dose
• Active alcohol abuse syndrome
• Subjects with a history of hepatitis of any etiology or hepatic insufficiency
• Pregnant or nursing at the time of signing informed consent
• Known sensitivity to any study medication
• Unwilling or unable to complete study diary
• Any other condition or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with the protocol
Drug: EC-18, Drug: Placebo
Exploring Safety & Clinical Benefit of Anti-Influenza Immunoglobulin Intravenous in Hospitalized Adults With Influenza A
18 Years and over
• Provision of voluntary informed consent in writing by patient, or legally authorized representative.
• Age ≥ 18 years of age.
• Locally determined positive influenza A infection (Rapid Antigen (Ag) Test or PCR) from a specimen obtained within 2 days prior to randomization.
• Onset of symptoms ≤ 6 days before randomization, defined as when the patient first experienced at least one respiratory symptom or fever.
• Hospitalized (or in observation unit) with influenza, with anticipated hospitalization for more than 24 hours and will be/already are receiving antiviral SOC.
• Experiencing ≥ 1 respiratory symptom (ex. cough, sore throat, nasal congestion) and ≥ 1 constitutional symptom (ex. headache, myalgia, feverishness or fatigue).
• For women of child-bearing potential: willingness to abstain from sexual intercourse or use at least 1 form of hormonal or barrier contraception through Day 60 of the study.
• Willingness to have blood and respiratory samples obtained and stored.
• National Early Warning Score (NEW score) ≥ 3 at screening.
• Use of any investigational product within the past 30 days prior to screening.
• History of hypersensitivity to blood or plasma products (as judged by the site investigator).
• History of allergy to latex or rubber.
• Known medical history of IgA deficiency.
• Pregnancy or lactation.
• Medical conditions for which receipt of a 500 mL volume of intravenous fluid may be dangerous to the patient (e.g. decompensated congestive heart failure), based on investigator's medical opinion with careful consideration of lab results.
• Liver function: liver function test (LFT) > 2.5 times upper limit of normal (ULN).
• Renal Function: glomerular filtration rate (GFR) < 60 mL/min/1.73 m2 (age and sex adjusted).
• A pre-existing condition or use of a medication that, in the opinion of the site investigator, may place the individual at a substantially increased risk of thrombosis (e.g. cryoglobulinemia, severe refractory hypertriglyceridemia, or clinically significant monoclonal gammopathy).
• An opinion of the investigator that it would be unwise to allow participation of the patient in the study (the reason for exclusion of the patient must be documented).
• Receiving extracorporeal membrane oxygenation (ECMO).
• Anticipated life expectancy of < 90 days.
• Confirmed bacterial pneumonia or any concurrent respiratory viral infection that is not influenza A (ex. respiratory syncytial virus (RSV) infection).
Biological: FLU-IGIV, Other: Placebo for FLU-IGIV
Influenza A H3N2, Influenza A H1N1
influenza A, hospitalized, H1N1, H3N2, human flu, respiratory tract infection, serious illness, flu
Expanded Access Protocol to Provide Brincidofovir for the Treatment of Serious Adenovirus Infection or Disease
Provide patients with serious AdV infection or disease access to treatment with BCV.
2 Months and over
• Confirmed serious AdV infection based on clinical symptoms and laboratory testing showing AdV in the blood or other bodily fluids
• Able to swallow medication, either tablet or liquid
• Previous dosing with Brincidofovir
• If female, not pregnant or trying to become pregnant
BIOPIC: Fungal Biomarkers for Diagnosis and Response to Therapy for Pediatric Candidemia (BIOPIC)
120 Days to 18 Years old
Inclusion Criteria:1. Males or females age > 120 days and <18 years 2. Have at least one of the following conditions:
• admitted to a non-neonatal ICU with any underlying disease
• being transferred imminently to a non-neonatal ICU with any underlying disease
• have gastro-intestinal insufficiency (eg. chronic short-gut syndrome) and admitted to anywhere in the hospital
• have a hematological malignancy (limited to AML, ALL, non-Hodgkin's lymphoma and myelodysplastic syndrome) and admitted to anywhere to the hospital
• have a solid tumor malignancy and admitted to anywhere in the hospital
• have a solid organ transplant and be admitted to anywhere in the hospital
• have a hemopoietic stem cell or bone marrow transplant and be admitted to anywhere in the hospital
• have aplastic anemia and be admitted to anywhere in the hospital 3. Have ≥ 1 central catheter (arterial or venous) 4. Have ≥ 1 blood culture drawn for clinical concern of infection at time of enrollment 5. Clinician initiates and/or changes any systemic antimicrobial therapy at time of enrollment 6. Parental/guardian permission (informed consent) and, if appropriate, child assent. 7. For Aim 2: Each of the above AND a positive blood culture or sterile site culture for Candida spp. that turns positive between day 0 and day +14.
Exclusion Criteria:1. Diagnosis of an invasive fungal disease within the 30 days prior to the blood culture drawn of clinical concern of infection. 2. Previous inclusion in this study 3. Weight < 4 kg (Due to constraints of no more than 3 ml/kg of blood to be drawn over an 8 week period). Subjects that fall below 4 kg during the study period that blood draws are occurring will not have more than 0.75 ml/kg of blood drawn each time. 4. Patient receiving empiric anti-fungal therapy for prolonged neutropenia or fever that was started prior to the time of blood culture 5. If blood cultures obtained and anti-infectives are added/changed only as part of a local protocol and not dictated by clinical concern of infection
IPFN, Pediatric, Fungal, Biomarker Assays, Candida, Pediatric ICU patient
An Observational Study of Hepatitis C Virus in Pregnancy (HCV)
This multi-center observational study examines risk factors for HCV transmission from mother to baby.
Inclusion Criteria:1. Singleton pregnancy 2. An HCV antibody positive screen (case) measured using two FDA-approved ELISA tests, the Abbott Architect version 3.0 system and the Ortho HCV 3.0. 3. Gestational age at screening no later than 23 weeks and 6 days, and gestational age at enrollment no later than 27 weeks and 6 days, based on clinical information and evaluation of the earliest ultrasound as described below.
Exclusion Criteria:1. Planned termination of pregnancy 2. Known major fetal anomalies or demise 3. Intention of the patient or the managing obstetricians for the delivery to be outside a MFMU Network center, unless special provisions are made to insure infant follow-up at two and 18 months of age. 4. Participation in this study in a previous pregnancy. 5. Unwilling or unable to commit to 18 months of follow-up for HCV positive infants
Observational Study of Persons With Hepatitis B Virus Infection in North America
The primary purpose of this study is to describe participants with hepatitis B virus (HBV) infection and identify factors that may cause the disease to activate or worsen.
18 Years to 100 Years old
• INCLUSION CRITERIA:
• Written informed consent
• At least 18 years of age
• HBsAg-positive and either
• Anti-HDV positive
• Diagnosed with acute HBV infection or experiencing a hepatitis flare
• Immune tolerant or immune active phenotype
• Potentially eligible for the Immune Regulation and Costimulation in Natural History of Chronic Hepatitis B ancillary study. EXCLUSION CRITERIA:
• History of hepatic decompensation
• Hepatocellular carcinoma (HCC)
• History of solid organ transplantation or bone marrow transplantation
• Current hepatitis B antiviral treatment (except pregnant women and patients who are anti-HDV positive)
• Chronic immunosuppression therapy
• Known HIV co-infection (patients with HDV or HCV co-infection are not excluded)
• Medical or social condition which, in the opinion of the investigator, would make the patient unsuitable for the study or interfere with or prevent follow-up per protocol
• Unable or unwilling to return for follow-up visits
Chronic Hepatitis B e Antigen Positive, Chronic Hepatitis B e Antigen Negative
Cirrhosis, Natural History, Hepatitis B
Entecavir/Pegylated Interferon in Immune Tolerant Children With Chronic Hepatitis B Virus (HBV) Infection
The purpose of this study is to determine the safety and efficacy of treatment using a combination of drugs (entecavir and pegylated interferon) in children ages 3-<18 years old with immunotolerant chronic hepatitis B.
3 Years to 18 Years old
• Enrolled in & completed the baseline evaluation in NCT01263600 OR completed necessary components of NCT01263600 baseline evaluation by the end of the baseline visit.
• 3 to <18 years at time of randomization (day 0).
• Documented chronic HBV infection as evidenced by detection of HBsAg in serum for ≥ 24 weeks prior to baseline OR positive HBsAg and negative anti-HBc IgM within 24 weeks of baseline visit.
• Presence of HBeAg in serum at the last screening visit within 6 weeks of baseline visit.
• Serum HBV DNA level >10^7 IU/mL on at least 2 occasions at least 12 weeks apart during the 52 weeks before baseline visit. The HBV DNA levels must be within 6 weeks of baseline visit.
• ALT ≤60 U/l in males or ≤40 U/l in females, measured on at least 2 occasions, at screening (within 6 weeks prior to baseline visit) & at least 12 weeks prior to the screening visit & within the 52 weeks prior to baseline visit.
• Compensated liver disease, with normal total bilirubin (except if Gilbert's syndrome), direct bilirubin ≤0.5 mg/dL, INR ≤1.5, and serum albumin ≥3.5 g/dL.
• Creatinine clearance 90 ml/min.
• Absence of hepatocellular carcinoma on liver ultrasound in the past 48 weeks. Exclusion criteria:
• Presence of infection with HCV-RNA or anti-HCV, anti-HDV, or HIV at screening.
• Presence of another cause of liver disease or HCC (serum alpha-fetoprotein >50ng /ml).
• Evidence of decompensated liver disease (Childs B-C).
• History or other evidence of a medical condition associated with chronic liver disease (e.g., hemochromatosis, autoimmune hepatitis, alcoholic liver disease, toxin exposures).
• Females who are pregnant or breastfeeding.
• Adolescent females unwilling or unable to use an acceptable method of contraception if sexually active during the treatment period.
• Children currently breastfeeding while their mother is taking lamivudine, or those who were exposed to lamivudine for ≥24 weeks via maternal lamivudine treatment during pregnancy and/or while breastfeeding.
• Previous liver or other organ transplantation including engrafted bone marrow transplant.
• Hematological abnormalities during the screening period that contraindicate full dosing with study drugs, e.g absolute neutrophil count < 1.5 x 10^9 cells/L or platelet count < 120 x 10^9 cells/L.
• Known allergy to study drugs; peginterferon alfa-2a or entecavir.
• Treatment with systemic acyclovir or famciclovir within the previous 6 months.
• Need for ongoing use of any antivirals with activity against HBV during the course of the study or history of receiving treatment for HBV.
• Any use of illegal drugs OR use of alcoholic beverages which in the opinion of a study physician is sufficient to prevent adequate compliance with study procedures or increase the risk of pancreatitis or hepatotoxicity.
• History of immunologically mediated disease (e.g. inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune haemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis).
• History or other evidence of bleeding from esophageal varices or consistent with decompensated liver disease.
• History or other evidence of chronic pulmonary disease associated with functional limitation.
• History of significant cardiovascular diseases.
• History of a severe seizure disorder or current anticonvulsant use.
• History or other evidence of severe retinopathy.
• History of thyroid disease poorly controlled on prescribed medications. Participants with elevated thyroid stimulating hormone concentrations with elevation of antibodies to thyroid peroxidase and any clinical manifestations of thyroid disease are excluded.
• Concomitant use or use during ≤ 6 months prior to the first dose of study drug of anti-neoplastic, immunosuppressive, nephrotoxic or hepatotoxic medication, methadone, theophylline or medications that may affect renal excretion or hepatic metabolism are not permitted.
• Concomitant use of complementary or alternative medications purported to have antiviral activity.
• A participant may not be co-enrolled in another clinical trial where an investigational drug is administered.
• Any other condition or situation that in the opinion of a study physician would make the participant unsuitable for enrollment or could interfere with the participant participating in and completing the study.
Drug: Entecavir and peginterferon
A Randomized Trial to Prevent Congenital Cytomegalovirus (CMV) (CMV)
Cytomegalovirus (CMV) is a common virus that usually presents with few if any side effects. When first infected, some people may have symptoms similar to mononucleosis (i.e., fatigue, weakness, fever, swollen glands). Most people in the United States are infected during childhood or as adults if they work around children. Pregnant women, who have not been infected with CMV in the past and become infected during pregnancy (i.e. a primary infection), may cause their babies to get infected with CMV. Babies that are infected may develop permanent disabilities including hearing loss and a small portion will die from the infection. Currently it is not routine practice to screen pregnant women for CMV infection. Additionally, there is no agreement about how to evaluate and manage pregnant women infected with CMV for the first time. There is also no evidence that treatment is beneficial for the baby. The purpose of this research study is to determine whether treating pregnant women who have a primary CMV infection with CMV antibodies will reduce the number of babies infected with CMV.
• Diagnosis of primary maternal CMV infection on the basis of one of the following: 1. A positive CMV Immunoglobulin M (IgM) antibody and low-avidity maternal CMV Immunoglobulin G (IgG) antibody screen 2. Evidence of maternal seroconversion with development of CMV IgG antibody following a prior negative CMV screen
• Gestational age at randomization no later than 23 weeks 6 days based on clinical information and evaluation of the earliest ultrasound; or no later than 27 weeks 6 days for women with a positive IgM, negative IgG initially screened before 23 weeks who are rescreened after 2-4 weeks and have evidence of IgG seroconversion.
• Singleton pregnancy. A twin pregnancy reduced to singleton (either spontaneously or therapeutically) before 14 weeks by project gestational age is acceptable.
• Maternal CMV infection pre-dating pregnancy as defined by a high IgG avidity index or a positive IgG in the presence of a negative IgM.
• Known hypersensitivity to plasma or plasma derived products
• Planned termination of pregnancy
• Known major fetal anomalies or demise
• Maternal Immunoglobulin A (IgA) deficiency
• Planned use of immune globulin, ganciclovir, or valganciclovir
• Maternal renal disease (most recent pre-randomization serum creatinine ≥ 1.4 mg/dL; all women must have serum creatinine measured during the pregnancy and prior to randomization)
• Maternal immune impairment (e.g., HIV infection, organ transplant on anti-rejection medications)
• Findings on pre-randomization ultrasound suggestive of established fetal CMV infection (cerebral ventriculomegaly, microcephaly, cerebral or intra-abdominal calcifications, abnormalities of amniotic fluid volume, echogenic bowel or ascites). Abnormally low amniotic fluid volume is defined as no fluid prior to 14 weeks or maximum vertical pocket < 2 cm on or after 14 weeks gestation. Abnormally high amniotic fluid volume is defined as > 10 cm.
• Positive fetal CMV findings from culture (amniotic fluid) or PCR.
• Congenital infection with rubella, syphilis, varicella, parvovirus or toxoplasmosis diagnosed by serology and ultrasound or amniotic fluid testing.
• Intention of the patient or of the managing obstetricians for the delivery to be outside a Maternal-Fetal Medicine Units Network (MFMU) Network center
• Participation in another interventional study that influences fetal or neonatal death
• Unwilling or unable to commit to 2 year follow-up of the infant
Drug: CMV hyperimmune globulin, Other: Placebo
Congenital Cytomegalovirus Infection, Maternal Cytomegalovirus Infection
Perinatology, Cytomegalovirus immune globulin, Cytogam, CMVIG infusions