Cooperative Agreement U24HL163316

2/2 CIRCULATORY SUPPORT IN PEDIATRIC HEART FAILURE PATIENTS USING THE JARVIK 2015 LVAD: A PIVOTAL TRIAL - PROJECT SUMMARY/ABSTRACT THIS COLLABORATIVE GRANT APPLICATION PROPOSES (A) TO CONDUCT A MULTICENTER SINGLE-ARM PIVOTAL CLINICAL TRIAL OF THE JARVIK 2015 LEFT VENTRICULAR ASSIST DEVICE (LVAD) AS A BRIDGE-TO-TRANSPLANT IN 22 HOSPITALIZED CHILDREN WITH SEVERE HEART FAILURE (HF) REFRACTORY TO MEDICAL THERAPY; AND (B) TO GENERATE THE SAFETY AND EFFECTIVENESS DATA NECESSARY TO SUPPORT REGULATORY REVIEW AND POTENTIAL FDA APPROVAL OF THE JARVIK 2015 LVAD UNDER THE HUMANITARIAN DEVICE EXEMPTION (HDE) PATHWAY. THE HDE PATHWAY IS FDA'S APPROVAL PROCESS FOR HIGH-RISK MEDICAL DEVICES INTENDED TO TREAT RARE AND/OR ORPHAN DISEASES. THE NEED FOR SAFE, RELIABLE, AND DISCHARGEABLE LVADS FOR SMALLER CHILDREN WITH HF IS WELL-ESTABLISHED. CURRENTLY, THE BERLIN HEART EXCOR PEDIATRIC VAD IS THE ONLY FDA-APPROVED DURABLE VAD FOR SMALLER CHILDREN. WHILE OUTCOMES HAVE IMPROVED, THE BERLIN HEART HAS IMPORTANT LIMITATIONS: (1) PATIENTS CANNOT BE DISCHARGED ON VAD SUPPORT; (2) THE PARACORPOREAL DESIGN, WITH LARGE-BORE CANNULAE TRAVERSING THE ABDOMINAL WALL RESULTS IN A HIGH INCIDENCE OF WOUND COMPLICATIONS; AND (3) THE HIGH PUMP THROMBOGENICITY (ESPECIALLY AROUND THE VALVES) REQUIRES INTRAVENOUS ANTICOAGULANTS AND INTERMITTENT PUMP EXCHANGES TO PREEMPT THE RISK OF STROKE. THERE IS AN ENORMOUS TECHNOLOGY GAP BETWEEN CONTEMPORARY ADULT VADS (CONTINUOUS FLOW [CF], MAGNETICALLY-LEVITATED, AND SAFELY DISCHARGEABLE) AND CONTEMPORARY PEDIATRIC VADS (PULSATILE, PNEUMATICALLY DRIVEN, NON-DISCHARGEABLE). IN RECENT YEARS, THE JARVIK 2015 LVAD, A FULLY IMPLANTABLE CF DEVICE HAS EMERGED AS AN ALTERNATIVE TO THE BERLIN HEART. DATA FROM THE FDA'S EARLY FEASIBILITY STUDY (EFS) SUGGEST THE JARVIK 2015 LVAD CAN SUPPORT SMALLER CHILDREN SUCCESSFULLY FOR UP TO A YEAR OR LONGER AS A BRIDGE TO TRANSPLANT. HOWEVER, SYSTEMATIC DATA IN A 22-SUBJECT INVESTIGATIONAL DEVICE EXEMPTION (IDE) PIVOTAL TRIAL IS REQUIRED FOR FDA REVIEW AND APPROVAL. THE SAFETY ENDPOINT IS FREEDOM FROM DEVICE-RELATED STROKE. THE EFFECTIVENESS ENDPOINT IS SURVIVAL TO TRANSPLANT OR 180 DAYS IN THE ABSENCE OF SEVERE STROKE. THE IDE RECEIVED CONDITIONAL FDA APPROVAL ON JUNE 4, 2021 (IDE# G160185). THE TRIAL WILL BE CONDUCTED AT 14 CENTERS IN THE US AND EUROPE WITH A CLINICAL COORDINATING CENTER AT STANFORD UNIVERSITY AND A DATA COORDINATING CENTER AT HEALTHCORE, INC. THE INVESTIGATOR GROUP HAS A STRONG HISTORY OF COLLABORATIVE RESEARCH AND MULTICENTER CLINICAL TRIALS, FACILITATING SMOOTH EXECUTION OF THE PROPOSED STUDY. IN ACCORDANCE WITH FDA'S REQUIREMENTS FOR APPROVAL OF HUMANITARIAN DEVICES, A PRE-SPECIFIED PERFORMANCE GOAL WILL DEMONSTRATE SAFETY AND EFFECTIVENESS (=17 OF 22 SUBJECTS FREE OF STROKE, AND =17SUBJECTS SURVIVING TO TRANSPLANT OR 180 DAYS FREE OF SEVERE STROKE: WITH CENTRAL REVIEW OF CLINICAL EVENTS AND NEUROIMAGING STUDIES). WHILE SAFE, RELIABLE, AND DISCHARGEABLE LVADS ARE WIDELY AVAILABLE FOR ADULTS, PEDIATRIC VAD TECHNOLOGY LAGS BEHIND BY MULTIPLE GENERATIONS OF TECHNOLOGY. MOREOVER, CHILDREN WHO SAFELY SURVIVE THEIR VAD COURSE HAVE A SUBSTANTIALLY LONGER POTENTIAL LIFE EXPECTANCY MAKING EVALUATION OF NEWER PEDIATRIC VADS AN URGENT PRIORITY FOR THE HEART FAILURE COMMUNITY. THIS TRIAL HAS THE POTENTIAL TO TAKE A CRUCIAL STEP IN ACHIEVING THAT GOAL.