Heart Transplant Clinical Trials

Cedars-Sinai Heart Institute is currently conducting the following Heart Transplant Research trials:

 

Early Invasive Monitoring Attenuation through Gene Expression (EIMAGE)

IRB Approval No.: 21046

Status: Enrollment Complete/Publication Pending

Project Summary: The purpose of this study is to compare the safety and effectiveness of gene expression blood tests to the commonly used method of heart biopsies for monitoring acute rejection in patients who have had a heart transplant. The study aims to demonstrate that acute rejection of the transplanted heart can be safely monitored using this blood test, first commercially introduced in 2005, so that repeated heart biopsies can be avoided. This blood test, called Gene Expression Profiling (GEP) identifies the expression of genes on white blood cells that circulate in the blood and cause the heart to be rejected. Results from the trial were presented at the 2013 International Society for Heart & Lung Transplantation Annual Meeting and Scientific Sessions in Montreal, Canada. A manuscript is currently in progress, with expected publication later this year.

 

Clinical Trials in Organ Transplantation (CTOT-11): Novel Therapies to Improve Renal and Cardiac Allograft Outcomes

IRB Approval No.: 23815

Status: Enrolling

Contact: Meridythe Washington, Study Coordinator, (310) 248-7132

Project Summary: Transplantation is the ideal therapy for end stage heart and end stage kidney failure, but allograft survival and function remain suboptimal. The overriding clinical hypothesis is that specifically designed therapies guided by rationally chosen noninvasive immune monitoring will improve outcomes in heart and kidney transplant recipients. The study involves identifying heart transplant candidates at high risk for antibody mediated injury (high PRA) and performing a pilot study to determine the safety and efficacy of desensitization using a combination of B cell depletion (rituximab) and IVIG plasmapheresis. The study will test the hypothesis that desensitization will lower PRA, diminish the waiting time to heart transplantation and result in acceptable 1 year graft survival and function. Associated mechanistic studies will determine how the desensitization protocol impacts preformed alloreactive T and B cell immunity and will test the hypothesis that residua l B and T cell immune memory with reactivity to donor antigens mediates post-transplant allograft injury.

 

Clinical Trials in Organ Transplantation (CTOT-13): A prospective, randomized, multicenter, two-parallel arm study evaluating the overall efficacy and safety of desensitization therapy on select sensitized patients awaiting heart transplantation

IRB Approval No.: 29841

Status: Enrolling

Contact: Meridythe Washington, Study Coordinator, (310) 248-7132

Project Summary: Because it has been difficult to find appropriate organs for highly sensitized heart transplant candidates, several groups have developed desensitization approaches aimed at removing or blocking the effector functions of preformed antibodies. This study is a controlled pilot trial with associated mechanistic studies to assess the safety, efficacy and associated mechanisms of desensitization therapy in heart transplantation using a strategy that includes plasmapheresis and bortezomib pre-transplantation. The evaluation of efficacy is defined by a lower complication rate while on the heart transplant waitlist. The secondary objective is to determine if desensitization therapy for the sensitized patient decreases pre-transplant morbidity and mortality on the waiting list and improves post-transplant outcomes.

 

Endothelial Cell Replacement by the host after Heart Transplantation and its Correlation with DSA Level and Allograft Outcome

IRB Approval No.: 31597

Contact: Frank Liou, Research Coordinator, (310) 248-7132

Project Summary: The presence of recipient derived endothelial cells in the donor organ is known as endothelial chimerism in transplanted organs. Since the 1960s, there is rising evidence for cell traffic from the graft into the host and vice versa following solid organ transplantation, and it is becoming clear that these processes influence whether an allograft is accepted or rejected. The migration of recipient endothelial cells into transplanted organs is of special interest, as this form of cell migration may play a key role in allograft acceptance. Despite the clear and widely accepted negative correlation of donor-specific antibodies and long-term allograft outcome in solid organ transplantation, there are still a number of patients presenting with donor specific antibodies that do not interfere with allograft function, even for a long period of time. We hypothesize, that in these patients, endothelial chimerism led to a tolerance of the recipient immune system towards the foreign organ, therefore leading to stable allograft function despite the presence of donor specific antibodies. This study will test for endothelial cell replacement in existing stored biopsy samples of patients one year post heart transplantation. Our aim is the evaluation of endothelial cell chimerism in cardiac allografts, its correlation to donor specific antibody level and its impact on allograft outcomes. The results may help to better understand the mechanisms of graft acceptance and rejection and thus may help in the decision whether a patient with donor specific antibodies after organ transplantation needs further therapy or not.

 

Heartsbreath Test for Heart Transplant Rejection

IRB Approval No.: 23823

Status: Enrollment Complete

Contact: Lucilla Garcia, Study Coordinator, (310) 248-7132

Project Summary: This research will evaluate whether the Heartsbreath device can assist in diagnosing heart transplant rejection in patients who have received a heart transplant during the preceding 12 months and are about to receive an endomyocardial biopsy. The main aim of this study is to validate the accuracy of the device to detect heart transplant rejection, by collecting samples prior to biopsy and comparing them with the biopsy results. Patients who have received a heart transplant within the previous 12 months and are scheduled for a routine endomyocardial biopsy may be eligible for participation in this trial. The breath test uses biomarkers found in human breath as indicators for rejection and its intensity. A screening breath test could potentially identify transplant recipients at low risk of Grade 3 rejection and reduce the number of endomyocardial biopsies. This multi-center trial is expected to complete enrollment in August 2013.

 

ACE Inhibition and Cardiac Allograft Vasculopathy

IRB Approval No.: 24970

Status: Enrolling

Contact: Lucilla Garcia, Study Coordinator, (310) 248-7132

Project Summary: The purpose of this study is to investigate the effect of the Angiotensin Converting Enzyme Inhibitor (ACE I), ramipril, an antihypertensive agent, on the development of Cardiac Allograft Vasculopathy (CAV) in cardiac transplant recipients in a randomized, double-blind, placebo-controlled study. Cardiac allograft vasculopathy (CAV) is a leading cause of morbidity and mortality after heart transplant. Despite advances in prophylaxis against rejection and infection, as well as improved control of traditional atherosclerotic risk factors, significant development of atherosclerotic plaque and detrimental vascular remodeling occur early after orthotopic heart transplantation (OHT). The investigators hope to determine whether ACE I therapy with ramipril early after OHT impacts the development of CAV, and learn if the use of ACE I increases the number of circulating endothelial progenitor cells (EPC) resulting in improved endothelial function and less atherosclerosis. The primary objective is to investigate the effect of ACE I on the development of CAV in cardiac transplant recipients in a randomized, double-blind, placebo-controlled study.

 

Long Term Outcome Follow-Up of the RAD001 B253 Study, Everolimus for the Prevention of Allograft Rejection and Vasculopathy in Cardiac-Transplant Recipients

IRB Approval No.: 26266

Project Summary: Survival for transplant recipients is still limited by cardiac allograft vasculopathy (CAV), infectious complications, malignancy, and rejection. In the landmark heart transplant study RAD001 B253 with all groups given cyclosporine, both doses of everolimus (1.5 and 3 mg/day) were superior to azathioprine for efficacy failure at 6, 12, and 24 months post transplantation. This finding was primarily due to a reduction in the incidence of acute rejection (ISHLT ≥ grade 3A) in the everolimus groups. The RAD B253 study also confirmed that everolimus appeared to be more beneficial than azathioprine in reducing the severity and incidence of CAV at 1-year post transplantation. However, the long term benefit of everolimus in heart transplant patients has yet to be established and thus, a study evaluating long-term outcomes is warranted. The purpose of the this study is to compare the 10-year outcomes of cardiac transplant patients originally randomized to evero limus 1.5mg, everolimus 3.0mg and azathioprine groups from the multi-center RAD001 B253 study. These outcomes include survival, cardiac allograft vasculopathy (CAV) by angiography, and non-fatal major adverse cardiac events. This is an investigator-initiated study where Cedars-Sinai is serving as the coordinating site, gathering long-term follow up data on patients from the original study.

 

Prospective, Multi-Center, Randomized Clinical Investigation of Transmedics Organ Care System (OCS) for Cardiac Use

IRB Approval No.: 23931

Status: Enrolling

Contact: Maria Thottam, Study Coordinator, (310) 248-7132

Project Summary: The TransMedics Organ Care System is a portable organ perfusion and monitoring system intended to preserve a donated heart in a beating state during transport for the eventual transplantation into a recipient. The Organ Care System (OCS) maintains organ viability by providing a controlled environment, continuously perfusing the donated heart with warm, oxygenated blood, supplemented with the TransMedics Cardiac Solution Set. The blood is collected from the donor and is continuously circulated to the organ in a closed circuit along with the Cardiac Solution Set. The OCS preserves the heart and monitors the organ’s perfusion parameters immediately after explanation from a donor and connection to the device, during transportation to the recipient site, and until disconnection from the device. The purpose of this study is to compare the safety and effectiveness of the OCS with the existing cold static cardioplegia standard of care for the preservation of donor hearts. To date, CSMC has enrolled 39 subjects in this study and is the highest enrolling site for this multi-center trial. Total study enrollment is expected to be complete by August 2013, with data analysis to follow.

 

The De-novo Use of Eculizumab Alongside Conventional Therapy in Presensitized Patients Receiving Cardiac Transplantation: An Open-Label, Investigator-Initiated

Pilot Trial: [The DUET Cardiac Trial]

IRB Approval No.: 28970

Status: Enrolling

Contact: Meridythe Washington, Study Coordinator, (310) 248-7132

Project Summary: The growing proportion of sensitized cardiac recipients presents an additional challenge to the transplant practitioner attempting to minimize the occurrence of antibody mediated rejection (AMR). Patients pre-exposed or "sensitized" to antigen exposing events (i.e.: blood transfusions, multiple pregnancies, prior organ transplantations, ventricular support devices) are more likely to both possess preformed and develop de-novo antibodies. Sensitized patients with panel reactive antibodies > 25% are at risk for increased mortality after heart transplantation. A central component of antibody-mediated cell injury is complement activation. The inhibition of terminal complement activation may be the missing link to decreasing possibly both complement-mediated AMR and cellular rejection (CR) by inhibiting both the inflammatory effects of both circulating antibodies and cytokine induced cell death. Eculizumab is a monoclonal antibody that specifically binds to complement protein C5 with high affinity, thereby inhibiting its cleavage to C5a and C5b and preventing the generation of the terminal complement complex C5b-9. By this mechanism, eculizumab (Soliris®) inhibits terminal complement mediated intravascular hemolysis in paroxysmal nocturnal hemoglobinuria patients. This study is a non-randomized, open-label, investigator-initiated safety and efficacy trial investigating the de-novo use of eculizumab alongside conventional therapy to prevent antibody mediated rejection. The duration of the study will include an open enrollment period and at least 12 months of follow-up (post-transplant). The trial will enroll a total of up to 10 "sensitized" patients with a panel reactive antibody score of greater than 70% and not previously or currently enrolled in another ongoing trial. At the time of initial baseline screening prior to transplantation, patients willing to consent to the investigational use of eculizumab will be enrolled in the treatment arm (comprising a maximum of 10 patients). The use of eculizumab will be un-blinded to all study and research practitioner participants. A historical cohort of 10 additional patients will also be utilized for comparison.

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