Clinical Research Directory

XVIVO Heart Perfusion System (XHPS) With Supplemented XVIVO Heart Solution (SXHS)

The purpose of this study is to evaluate if Non-Ischemic Heart Preservation (NIHP) of extended criteria donor hearts using the XVIVO Heart Preservation System (XHPS) is a safe and effective way to preserve and transport hearts for transplantation.

XVIVO Heart Box (XHB) With Supplemented XVIVO Heart Solution (SXHS) Continued Access Protocol (CAP)

The purpose of this study is to evaluate if Non-Ischemic Heart Preservation (NIHP) of extended criteria donor hearts using the XVIVO Heart Preservation System (XHPS) is a safe and effective way to preserve and transport hearts for transplantation.

HIIT in Pediatric Heart Transplant Recipients (MedBIKE™)

Heart transplantation is the long-term treatment for children and adults with advanced heart failure. Post-transplant outcomes have improved over time, such that 50% of pediatric heart transplant recipients (HTR) remain alive with a need for re-transplantation 17-years following the initial transplant. With improved short- and medium-term outcomes, focus has shifted towards optimizing long-term survival and reducing transplant-associated morbidities. This includes strategies aimed at optimizing cardiorespiratory fitness and physical activity levels. Pediatric and adult HTRs have reduced exercise capacity compared with the general population. Previous groups have shown gradual improvements in heart rate response to exercise and exercise capacity in pediatric HTRs. However, after an initial improvement, exercise capacity appears to plateau, or even decline in pediatric HTRs, and remains sub-optimal compared with the general population. Most exercise interventions in HTRs to date have focused on moderate-intensity continuous exercise (MICE), with some resistance components incorporated. More recently, high-intensity interval training (HIIT), consisting of short, intense bursts of exercise with rest periods, has been explored in the adult HTR population, with findings to date suggesting that it may yield greater improvements in cardiorespiratory fitness compared with MICE. Exercise interventions, particularly HIIT interventions, have consistently shown clinically important improvements in exercise capacity in adult HTRs that are linked with improved long-term post-transplant outcomes and well-being. Unfortunately, trials of exercise interventions in pediatric HTRs remain lacking. This study team is proposing an assessment of the feasibility of a home-based HIIT exercise program using a novel telemedicine-enable video game linked customizable cycle ergometer (MedBIKE™).

EXCOR Active Driving System for the EXCOR Pediatric VAD IDE Study

The purpose of this study is to evaluate the device performance and monitor the safety and effectiveness of the Berlin Heart EXCOR Active Driving System while being used with the approved EXCOR Pediatric Ventricular Assist Device. EXCOR Active Driving System is intended for use with the approved EXCOR Pediatric VAD. The EXCOR Pediatric VAD is intended to provide mechanical circulatory support as a bridge to cardiac transplantation for pediatric patients. Pediatric candidates with severe isolated left ventricular or biventricular dysfunction who are candidates for cardiac transplant and require circulatory support may be treated using the EXCOR Pediatric. EXCOR Active is intended for use in a clinical setting. EXCOR Active can be used in any kind of hospital unit (e.g. OR, ICU, intermediate care unit or general care unit). The driving unit may be moved between clinical units using the caddy or baby buggy; however, a patient must always be accompanied by a person trained in the use of the manual pump and emergency procedures during transport in the event of an emergency. The driving unit can be transported during operation.

Cardiopulmonary Stress Testing (CPET) AlloSure Study

1. Cell-free DNA does not vary significantly as a function of the activity of immunologically quiescent cardiac transplant recipients, despite the metabolic demands of the transplanted organ. (The implication of the null result would be that no restrictions to patient activity, nor modification of cardiac rehabilitation prescription, would be necessary to maintain proper test characteristics of AlloSure testing). 2. In immunologically active cardiac transplant allografts, exercise prior to assay of donor-derived cell-free DNA can be used to increase the sensitivity of the AlloSure test. (The implication of this would be that the optimal time-frame for drawing an Allosure may actually be post-exercise, and that window will be characterized).

The Hepatitis C Transplant Collaborative

In this study we seek to test the hypothesis that safety and clinical outcomes after cardiac transplantation utilizing HCV NAT+ donor organs as currently performed are acceptable.

Non-ischaemic Heart Preservation Versus Standard Cold Storage in Human Heart Transplantation

The overall aim of this study is to compare a new state-of-the-art ex-vivo organ preservation method with standard ischemic cold static storage of donor hearts in adult cardiac transplantation. Standard heart preservation before transplantation consists of cold ischemic storage of the heart. Clinical studies have shown that the morbidity and mortality risk increases with the extension of the allograft ischemic time over four hours. For each additional hour the mortality risk increase with 25% the first year. This time constraint is costly and results in severe logistical problems, leading to loss of transplantable organs. The preliminary results from our safety study, where six patients transplanted with the new state-of-the-art ex-vivo organ preservation method, have shown promising results. The study is a multicenter, prospective, open, blinded endpoint, randomized, controlled clinical trial. The primary end-point is survival free of acute cellular rejection (ACR) and retransplantation within 1-year post-transplant. ACR will be assessed blinded. The secondary end-points are ischemia/reperfusion injury, early graft dysfunction, and QoL.

HEARTBiT: Multi-Marker Blood Test for Acute Cardiac Transplant Rejection

Heart transplantation is a life saving therapy for people with end stage heart failure. Acute rejection, a process where the immune system recognizes the transplanted heart as foreign and mounts a response against it, remains a clinical problem despite improvements in immunosuppressive drugs. Acute rejection occurs in 20-30% of patients within the first 3 months post-transplant, and is currently detected by highly invasive heart tissue biopsies that happen 12-15 times in the first year post-transplant. Replacing the biopsy with a simple blood test is of utmost value to patients and will reduce healthcare costs. The goal of our project is to develop a new blood test to monitor heart transplant rejection. Advances in biotechnology have enabled simultaneous measurement of many molecules (e.g., proteins, nucleic acids) in blood, driving the development of new diagnostics. Our team is a leader in using computational tools to combine information from numerous biological molecules and clinical data to generate "biomarker panels" that are more powerful than existing diagnostic tests. Our sophisticated analytic methods has recently derived HEARTBiT, a promising test of acute rejection comprising 9 RNA biomarkers, from the measurement of 30,000 blood molecules in 150 Canadian heart transplant patients. Our objective is to study a custom-built HEARTBiT test in a setting and on a technology that enable clinical adoption. We will evaluate the new test on 400 new patients from 5 North American transplant centres. We will also track patients' HEARTBiT scores over time to help predict future rejection, and explore use of proteins and micoRNAs to improve HEARTBiT. Our work will provide the basis for a future clinical trial. The significance of this work rests in that it will provide a tool to identify acute cardiac rejection in a fast, accurate, cost-effective and minimally invasive manner, allowing for facile long-term monitoring and therapy tailoring for heart transplant patients.

Impact of SGLT2 Inhibitors in Heart Transplant Recipients

The goal of this clinical trial is to test if SGLT2 inhibitors could prevent or delay the development of Cardiac Allograft Vasculopathy (CAV) post-heart transplantation (TxC). The main questions it aims to answer are: Primary outcome: CAV, according to ISHLT grading system diagnosed by CCTA; Secondary outcomes: cardiovascular death, all-cause mortality, hospitalization, worsening glomerular filtration rate, fasting glucose, weight, and blood pressure. Exploratory and safety outcomes: Rejection, hypoglycemia, urinary tract infection, hypovolemia, and limb amputation. HYPOTHESIS The null hypothesis is that SGLT2 inhibitors do not reduce the incidence of CAV in transplanted patients. The alternative hypothesis is that SGLT2 inhibitors reduce the incidence of CAV in transplanted patients.METHODOLOGY Study Design A randomized clinical trial of superiority with active control (2 arms), with central randomization and blinded evaluation of outcomes, to evaluate the efficacy and safety of adding dapagliflozin or empagliflozin 10 mg once daily to conventional post-TxC treatment compared with the treatment of isolated conventional post-TxC for 6-8 months. Study Sample Sample: All adult patients undergoing a heart transplant between January 2017 and December 2023 at Hospital de Messejana. Inclusion Criteria Included: Patients of both sexes, aged ≥ 18 years, who have undergone heart transplantation between January 2017 and December 2023 and are under the care of the Heart Transplant and Heart Failure Unit at Hospital de Messejana.

EASE-SOT Pilot Study

Many transplant recipients may experience physical and emotional symptoms, such as anxiety, fatigue, sleep problems, pain, etc. Often, these symptoms are not reported or managed well, and can affect a patient's quality-of-life. Transplant recipients are grateful for the "gift of life" but physical and emotional symptoms reduce their quality-of-life. Transplant recipients and caregivers have felt unprepared for the ongoing symptoms and reduced quality-of-life post-transplant. One way of monitoring and managing these symptoms is using the Emotion And Symptom-focused Engagement (EASE) intervention. EASE was originally developed for patients with acute leukemia and has begun to be adapted to help monitor and manage physical and emotional symptoms for organ transplant recipients. EASE is comprised of two components: 1. Psychological - 8 supportive counselling sessions delivered by mental health clinicians to address concerns about mental health, losses from organ failure, coping with a transplant, experiences with living on the brink of death for a prolonged period of time, etc. 2. Physical - Regular assessments of physical symptoms using questionnaires and referral to healthcare professionals for symptom management as necessary. EASE uses questionnaires, also called patient reported outcome measures (PROMs), for symptom assessment and monitoring. PROMs measure symptom severity, similarly to how bloodwork measures organ functioning. PROMs, as part of EASE, will ask recipients questions and help identify relevant physical, emotional, and social symptoms to enhance their care. With the help of specialists, patients, and support from the Kidney Foundation of Canada, our team has begun to adapt the EASE intervention for transplant recipients. In order to finalize the adaptation of the EASE intervention for use in a routine transplant clinic, we are launching a pre-pilot study to gain real-life experience from managing symptoms of SOT recipients with the use of EASE-SOT.