Multicenter Trial of ECMO in Children With Severe Cardiac Failure Using the Cardiohelp System

This is a multicenter clinical trial to evaluate the safety and effectiveness of the Cardiohelp System for up to 30 days of support in children with severe cardiac failure. The trial includes a secondary randomized study comparing heparin versus bivalirudin anticoagulation according to standard treatment protocols. Despite more than 50 years of ECMO use that carries up to 50% mortality, no standalone ECMO device has ever received FDA clearance for pediatric ECMO. All ECMO use in children is off-label, which may contribute to substantial mortality and complications, as well as wide center-to-center variation in ECMO practices that lacks an evidence base. Additionally, while two anticoagulants (heparin and bivalirudin) are commonly used in ECMO circuits, the optimal choice remains unknown-specifically, which anticoagulant is associated with the fewest circuit clots and least bleeding. This study, funded by an R01 clinical trials Orphan Grant from the FDA, seeks to change the current status quo. By collecting systematic safety and effectiveness data on the Cardiohelp Device, we aim to determine whether it is safe and effective enough to become the first standalone ECMO device to receive FDA clearance for up to 30 days of support in children. The FDA clearance decision will be based on how the Cardiohelp performs relative to several key performance benchmarks drawn from the published ECMO literature, which the FDA has jointly agreed upon. These benchmarks include overall survival without severe stroke, degree of hemolysis (red blood cell breakdown), frequency of circuit change due to thrombus or device malfunction, stroke rate, and kidney injury rate. For the anticoagulant randomized trial, we will collect systematic data on clotting and bleeding complications associated with each anticoagulant. As a Phase II study, the goal is not to reach a final answer, but to design a Phase III (pivotal) trial that is as informative and efficient as possible for addressing this critical question in the field of ECMO. Tertiary goals of the study are: (1) to determine the optimal performance range (i.e., device specifications) for the Cardiohelp device in children to inform an eventual FDA label and Instructions for Use (IFU); and (2) to provide the FDA with a predicate device to support FDA clearance of other ECMO systems under 510(k) regulation, as no predicate devices currently exist to support such regulatory comparisons.