335 Clinical Trials for Various Conditions
This study aims to develop and refine a miR biomarker panel that can be used to phenotype net immune state after heart transplantation.
Cardiac Failure, Graft Rejection
This will be a prospective single-center interventional trial to compare the outcomes of HIV-positive heart transplant recipients by the HIV status of the donor; HIV-positive vs. HIV-negative and learn whether heart organ transplantation from HIV+ deceased donors is as safe and effective in HIV+ recipients as transplants from HIV- deceased donors. Patient will undergo standard evaluation for eligibility of transplantation by the primary heart transplant team. If patient meets eligibility criteria, they will be informed about the study and consent will be obtained. Informed consent will be obtained in a private clinic or inpatient hospital room in a confidential setting. HIV-positive or HIV-negative offers will be made by Organ Procurement and Transplantation Network (OPTN) (serving as a means of "natural randomization" and this information will also be collected, along with the information regarding any information for primary offer declines from the patients as well as other clinical indications to decline an organ offer. As a result of this, there will be two main groups in the study participants that will undergo analysis: 1. patients/recipients that are HIV+ who receive an organ from an HIV+ donor (HIV D+/R+ group) 2. patients/recipients that are HIV+ who receive an organ from an HIV negative donor (HIV D-/R+ group) Only study participants will be able to receive organ offers from both HIV-positive and HIV-negative organ donors whichever is available first regardless of HIV status. This is the only study intervention. Baseline visit parameters will be obtained during a routine heart transplant visit. There will be no additional procedures or blood collection after the baseline study visit. Study data will be collected from chart review of routine post-transplant follow-up visits at weeks 52 (1 year), 104 (2 years), and 152 (3 years) after the transplant.
HIV Infection, Advanced End Stage Heart Failure
Heart transplant (HTx) is an established therapy for advanced heart disease that restores quality of life and improves survival. However, due to preexisting comorbidities combined with the immunosuppressive therapies required after transplantation, HTx recipients remain at high risk for kidney, cardiovascular (CV), and metabolic disease. Large randomized clinical trials have recently shown that sodium-glucose cotransporter 2 inhibitors (SGLT2i) have potent kidney protective and CV benefits in many populations of patients with chronic kidney disease (CKD), CV disease and/or diabetes. SGLT2i have not been studied prospectively in HTx recipients, which represents a barrier to their use in this population. In this multicenter randomized controlled trial in Veterans with HTx, investigators will evaluate the potential benefits of empagliflozin on kidney function, cardiometabolic risk, erythropoiesis, and functional status. A total of 200 Veterans will be randomly assigned to receive either empagliflozin 10 mg daily or a matching placebo for 12 months.
Heart Transplant, Cardiovascular Disease, Kidney Disease
This study aims to discover circulating microRNAs (associated with drug doses and levels) that can be used to characterize the overall immune state in pediatric heart transplant patients and predict patients that will go on to develop infection and rejection. MicroRNAs (miRs) are small, non-coding RNA molecules that regulate gene expression and serve as molecular biomarkers found in the circulation.
Cardiac Failure, Graft Rejection
This is a phase 2, prospective, multi-center, open-label clinical trial. Sixty-six (66) primary heart transplant recipients will be randomized (1:2) to receive either standard-of-care, tacrolimus-based immunosuppression, or a belatacept-based regimen with gradual tacrolimus withdrawal over 9-months post-transplant. Both study arms will receive CellCept® (mycophenolate mofetil- MMF) or Myfortic® (mycophenolate sodium). Corticosteroids will be continued throughout the study in the belatacept arm. The primary objective is to evaluate whether NULOJIX® (belatacept), when implemented with gradual tacrolimus withdrawal over 9 months, is safe with respect to preventing the composite endpoint of acute cellular rejection (ACR) \>= International Society of Heart and Lung Transplantation (ISHLT) 2R, hemodynamic compromise rejection in the absence of a biopsy or histological rejection, re-transplantation, and death at 18 months post-transplant.
Heart Transplant
This will be a prospective, randomized study performed at a single tertiary referral academic medical center (University of California San Francisco, CA), evaluating the survival benefits of levothyroxine compared with no levothyroxine for patients who have undergone heart transplant. It will be double-blinded and placebo-control; participants will be randomized to receive levothyroxine or receive no levothyroxine.
Heart Transplant Failure, Heart Transplant Infection
This is an open label Comparative Effectiveness Research (CER) study in which patients will be randomized at the site level to Prospera surveillance or EMB surveillance in a 2:1 ratio (Prospera to EMB) at each site. Subjects will be enrolled into the study while under evaluation for heart transplantation or on the transplant waiting list prior to heart transplantation. All subjects will follow the center's standard of care surveillance schedule from transplant through 4 weeks post-transplantation. EMB during this phase is expected to occur roughly weekly or bi-weekly. Study group assignment will take place at randomization. Subjects will be randomized 30 days (± 10 days) post-transplant to Prospera surveillance versus EMB surveillance in a 2:1 ratio. Rejection surveillance (Prospera Group and EMB Group) will be performed at times corresponding to the institutional standard of care schedule for rejection surveillance.
Heart Transplant Failure and Rejection
This research study is investigating whether completing breathing exercises before surgery helps heart transplant patients recover after surgery. Previous studies have shown that breathing exercises can improve breathing, cough, and swallow function in patients with other diseases/conditions. The current study will investigate the impact of a preoperative respiratory muscle strength training program on breathing and cough function, swallow function, patient-reported eating and swallowing fatigue, and health outcomes in individuals undergoing heart transplantation. Participants will: * undergo tests of breathing, cough, and swallow function * complete questionnaires about the treatment, their swallow function * complete breathing exercises daily
Dysphagia, Heart Transplant Recipients
The purpose of this research is to detect episodes of rejection versus non-rejection after cardiac transplant and the diagnostic accuracy of an Artificial Intelligence (AI) algorithm using the data from an ECG (electrocardiogram) and Cardiac Ultrasound (Echocardiogram and/or point of care ultrasound).
Cardiac Transplant Rejection
Following orthoptopic heart transplantation (OHT), children undergo surveillance cardiac catheterizations to assess for signs of rejection including muscle biopsy as well as pressure measurements to guide post transplant treatment regiments. These procedures are done under general anesthesia which promotes lung tissue collapse (atelectasis). What is not known is the effect of atelectasis on intracardiac pressures which are a critical area of monitoring post-transplant patients for rejection.
Heart Transplant Failure, Anesthesia
The purpose of this study is to determine if a partial heart transplantation in patients with congenital heart disease is safe and feasible. Participants will have a partial heart transplant involving surgical replacement of the pulmonary valve with the heart valve and supporting blood vessels from an organ donor. The procedure, tests, medications, and follow-up visits will all be done per standard of care. Medical data will be collected to look at outcomes after surgery.
Congenital Heart Disease
We will conduct a two-group randomized controlled trial to examine the eMocha DOT intervention with pediatric HT recipients.In this population, medication nonadherence remains a primary cause of late acute rejection (LAR) episodes, increased number of hospitalizations, graft failure, and patient mortality. Herein, we propose an innovative approach to promote medication adherence and improve patient and graft outcomes.
Heart Transplant Rejection, Immune Suppression, Pediatric Heart Transplant, Medication Nonadherence, Health Behavior, Remote Monitoring, Patient Engagement
Heart transplantation (HTx) is a well-established life-saving procedure but is associated with severe complications. Regular monitoring of heart transplant recipients is thus important for the early detection of these complications. Current standard clinical tests, however, rely on frequent invasive procedures including endomyocardial biopsies (EMB) and catheter angiography (Cath). In addition, these standard tests are limited by sampling error, the diffuse nature of HTx complications, and high health care utilization cost, estimated at \>$150,000 per year per patient in the US. To address these limitations, our group has developed a non-invasive multiparametric cardiac MRI, which can quantify abnormal changes in heart tissue and function. Our efforts during the initial period of this study (NIH funded 2014-2019) have focused on the two major complications of HTx: 1) acute cardiac rejection (ACR), the leading cause of death in the first year after heart transplant; and 2) cardiac allograft vasculopathy (CAV), the greatest risk factor for 5-year mortality beyond the first year after heart transplantation. For these major compilation, our previous cardiac MRI studies have identified new non-invasive cardiac MRI measures that can detect abnormalities of heart tissue and function. In addition, the data was able to show that heart donor and recipient mismatch (age, sex, height, weight, etc.) can cause changes in tissue and function of the transplanted heart.
Transplant, Heart, Magnetic Resonance Imaging
Transthyretin cardiac amyloidosis (ATTR-CA) is a relentlessly progressive disease that can progress to end stage heart failure, at which point recently approved transthyretin production silencing or structure stabilizing therapies provide no clinical benefit. For well-selected individuals, heart transplantation is an excellent therapeutic option to improve survival. Historically, concomitant liver transplantation has been used to halt the progression of non-cardiac transthyretin amyloidosis (ATTR) manifestations, especially for individuals with TTR genotypes associated with significant neuropathy. However, despite this, patients continue to experience progressive non-cardiac manifestations, particularly gastrointestinal and neuropathic, which can have a substantial influence on post-heart transplantation morbidity. Concomitant liver transplantation is also associated with substantial morbidity and its future therapeutic role is questionable with recently established therapies for ATTR. Therefore, there is a clear unmet need to determine the utility and safety of ATTR targeted therapies for patients with recent heart transplantation for end-stage ATTR-CA. The central hypothesis of this proposal is that in patients who have received a heart transplantation for end-stage ATTR-CA, tafamidis therapy will be efficacious and well-tolerated. We aim to determine the safety and efficacy of tafamidis in stable patients who have undergone heart or combined heart/liver transplantation for ATTR (wild-type or variant) cardiac amyloidosis. The proposed study will be a single-arm intervention clinical trial with tafamidis. Because of the efficacy of tafamidis for both variant ATTR-CA and wild-type ATTR-CA, there is no clinical equipoise for an inactive-comparator placebo arm. The primary endpoint of this study will be serial change in plasma transthyretin (TTR) levels from baseline to 12 months at 3-month intervals. The secondary endpoints of this study will include serial changes in neuropathy assessments, modified body mass indices, incident transplant-specific adverse events, and pharmacokinetics of tafamidis. Observations from this study will establish the role of tafamidis use for the management of ATTR in patients after transplantation for end-stage ATTR-CA.
Transthyretin Cardiac Amyloidosis
The aim of this 16-week group aerobic training program, delivered remotely via video-conferencing, is to assess program feasibility, and determine if program increases physical activity in adolescents after heart transplant.
Orthotopic Heart Transplant
The long-term goal of this research initiative is to develop a new valve replacement option for neonates, infants and young children. The central hypothesis is that transplantation of a freshly isolated heart valve will be associated with superior outcomes compared to currently available options, including preserved cadaver valves, bioprosthetic tissue valves, or mechanical valves. This new operation has been named "partial heart transplantation". The proposed study is a single-center, nonrandomized single arm pilot trial of "partial heart transplantation" in neonates, infants and young children who require semilunar heart valve replacement. This "first in man" trial seeks to determine whether valve replacement using partial heart transplant is feasible and safe. Primary aims are survival one year and five years following the procedure. The hypothesis is that, when compared to historical controls who have undergone homograft valve replacement, those undergoing partial heart transplantation will have equal or superior survival one year and five years following the procedure. Secondary aims are to assess growth and function of the transplanted valve. The hypothesis is that when compared to historical controls who have undergone conventional valve replacement, those undergoing partial heart transplantation will have valve growth that corresponds with somatic growth and superior valve function 1 year following the procedure. Up to five patients will be enrolled in this trial over three years.
Semilunar Heart Valve Replacement
This is a prospective, multicenter observational, unblinded, longitudinal cohort study. Subjects will be enrolled into the study prior to or at the time of heart transplantation. All subjects will follow the center's standard of care surveillance schedule. Blood samples will be collected for Prospera testing at the time any surveillance or for-cause testing, which may include endomyocardial biopsy (EMB), echocardiography or other cardiac imaging studies, and/or molecular testing, is performed.
Heart Transplant
This is a prospective, observational, pilot trial to evaluate the feasibility of heart transplantation using normothermic regional perfusion (NRP) donation after donor circulatory death (DCD). Adults who meet standard criteria for heart transplantation listing and study-specific eligibility criteria will enroll in the study. the investigators anticipate evaluating an initial cohort of approximately 100 DCD donors for a final yield of 40 hearts. The investigators will accept donors between the ages of 18 and 65 who are determined to have heart function/quality appropriate for donation for transplantation based on available donor data and testing. If feasible, donors might be relocated to BUMCP to maintain uniformity of process, minimize cold ischemic time, and allow for more rapid and improved communication during the initial pilot phase. Recipients will be selected based on blood group, crossmatch, size match, and clinical stability per standard allocation practices. Recipients will be followed post-transplantation per BUMCP Heart Transplant standard protocol.
Heart Transplantation, Perfusion, Transplant Recipients
The ProTECT registry is an observational longitudinal, multi-center study observing patients undergoing heart transplant for whom Prospera testing is part of routine clinical care, who are enrolled within 60 days of heart transplantation.
Heart Transplant Rejection
This is a prospective, pilot trial to evaluate the safety and effectiveness of The Paragonix SherpaPak™ Cardiac Transport System ("SherpaPak CTS") in transportation of cardiac allografts recovered from donors after circulatory death with thoracoabdominal normothermic regional perfusion (TA-NRP). SherpaPak™ CTS is an ultraportable hypothermic preservation and transport system that has been approved by United States Food \& Drug Administration (FDA) for clinical use in heart transplantation.
Heart Transplant Failure, Determination of Death, Outcomes Research, Extracorporeal Membrane Oxygenation
This is an open label trial in which letermovir will be given as prophylaxis for the prevention of CMV infection and disease to all heart transplants who are at risk for cytomegalovirus. The study will compare a 30 patient prospective cohort to a retrospective cohort of 374 heart transplant recipients for the rates of neutropenia. In addition, the tolerability of letermovir will be assessed in this population.
Cytomegalovirus Disease, Cytomegalovirus Infections, Heart Transplant Infection, Antiviral Toxicity, Neutropenia
This is a prospective, observational, pilot trial to evaluate the feasibility of heart transplantation using normothermic regional perfusion (NRP) donation after donor circulatory death (DCD). Normothermic regional perfusion utilizes Extracorporeal Membrane Oxygenation (ECMO) or cardiopulmonary bypass to reperfuse the heart and other organs in situ after isolation and ligation of the cerebral vessels. In situ resuscitation of the heart has the added advantage of allowing full hemodynamic and echocardiographic assessment of the donor heart prior to final acceptance for transplantation without the imminent danger of ongoing warm ischemia.
Heart Transplant Failure, Determination of Death, Outcomes Research, Death
The purpose of this study is to test whether Daratumumab-SC, a drug that eliminates antibody-producing plasma cells, can effectively lower the level of preformed antibodies in patients awaiting heart transplantation. These preformed antibodies limit the number of donor hearts that are compatible for the patients. If Daratumumab-SC can effectively remove preformed, donor-specific antibodies, then highly allosensitized patients will have more compatible hearts available to them, potentially decreasing transplant waitlist time and reducing mortality.
Allosensitization, Heart Transplant Failure and Rejection
The purpose of this study is to determine if Belatacept is safe to give to adult heart transplant recipients. Belatacept (NULOJIX) is an anti-rejection medication that is available through a prescription from a doctor. In this research study, belatacept is being used in an investigational manner (not for the purpose that it is approved for).
Heart Transplantation
Immunosuppressive therapy is required to prevent organ rejection, however, dosing of immunosuppressive agents is complicated by patient-specific differences impacting the body's absorption and elimination of these agents. The goal of this research proposal is to clinically validate an innovative precision medicine strategy for dosing the immunosuppressant tacrolimus in pediatric heart transplant, which will in turn lead to improvements in long-term transplant survival outcomes. The strategy and techniques used in this project can be extended to improve drug therapy across multiple pediatric diseases requiring chronic therapy.
Heart Transplant Failure and Rejection
Normothermic regional perfusion (NRP) utilizes Extracorporeal Membrane Oxygenation (ECMO) or cardiopulmonary bypass to reperfuse the heart and other organs in situ after isolation and ligation of the cerebral vessels. In situ resuscitation of the heart has the added advantage of allowing full hemodynamic and echocardiographic assessment of the donor heart prior to final acceptance for transplantation without the imminent danger of ongoing warm ischemia.
Heart Failure
This project aims: i) to identify Cardiac Allograft Vasculopathy (CAV) trajectories after heat transplantation using latent class mixed modeling, ii) to characterize the global and specific determinants of different trajectories and iii) to provide an easily accessible tool to project individual probability of CAV trajectory belonging.
Heart Transplantation, Allograft Arteriopathy
Coronary allograft vasculopathy (CAV) is diffusely accelerated atherosclerosis of a transplanted heart. Evolocumab (Repatha) is an FDA-approved drug for lowering low density lipoprotein (LDL) in patients who have not received a heart transplant. This drug works as a PCSK9-inhibitor. The primary objective of this study is to measure the impact of PCSK9-inhibitors on serum LDL in heart transplant patients with CAV after 12 weeks compared to baseline.
Heart Transplant
The purpose of this post market surveillance is to continue monitoring the safety and effectiveness of the Berlin Heart EXCOR® Pediatric. This surveillance includes an "all-comers" prospective cohort of pediatric (\<22 years of age) patients implanted according to the IFU with the EXCOR® Pediatric.
Ventricular Dysfunction, Ventricular Dysfunction, Left, Ventricular Dysfunction, Right
The purpose of this research study is to see if a study drug called Tocilizumab will, when given with standard anti-rejection medicines, lead to better heart transplantation outcomes at 1 year after the transplant. Specifically, the investigators will evaluate whether taking tocilizumab leads to less rejection, less development of unwanted antibodies, and better heart function.
Heart Transplant