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

Overview

There are two primary goals of this multicenter clinical trial that combines an FDA device trial and a phase II drug trial in the same study cohort. These two goals are to: 1. To evaluate the safety and effectiveness of the Cardiohelp Device for VA-ECMO (heart-lung support) for up to 30 days of support in children with severe heart failure with the goal to support its FDA clearance in children. 2. To evaluate heparin versus bivalirudin as the primary blood thinner (anticoagulant) in a randomized trial of children supported with the Cardiohelp ECMO System with the goal to plan a phase III (pivotal) randomized clinical trial The main questions the Cardiohelp single-arm trial seeks to answer are: * What is the safety and effectiveness of the Cardiohelp device for pediatric ECMO? * Should the Cardiohelp device be FDA-cleared for children based on the results of the study? * What are the optimal performance specifications of the Cardiohelp device in children? The main questions the blood thinner randomized trial seeks to answer are: * Which blood thinner is more promising (i.e., more effective and safer) in children on the Cardiohelp device? * How should a pivotal trial of heparin vs. bivalirudin be designed so it is the most informative and efficient to determine the best blood thinner? Children who are receiving the Cardiohelp device will be approached and consented to participate if interested. For the Cardiohelp device trial, participants will undergo a standardized data collection to estimate survival to 30 days and the prevalence of serious adverse events like stroke, bleeding, and hemolysis. For the blood thinner randomized trial, participants will be randomized 1:1 to blood thinner strategy to determine which blood thinner has the fewest bleeding and clotting complications. For the Cardiohelp single-arm trial, participant outcomes will be compared to performance goals (PG) derived from the ECMO literature. For the blood thinner randomized trial, the amount of bleeding and clotting will be measured. The study is funded by an R01 grant from the FDA's Office of Orphan Product Development (OOPD).

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.