TITRE: Trial of Indication-Based Transfusion of Red Blood Cells in ECMO
Abstract
Background: Critically ill children with lungs and heart failure unresponsive to medical and surgical therapies can be rescued with invasive support called Extracorporeal Membrane Oxygenation (ECMO). Although lifesaving, half of all children supported with ECMO die during the hospital admission in which it is used, and survivors often suffer complications that can cause long-term disabilities and impaired quality of life. Rationale: While ECMO supports heart and lung function, delivery of oxygen to tissues to restore organ function requires the oxygen-carrying molecule, hemoglobin (Hb) present in red blood cells (RBCs). Children on ECMO often receive frequent RBC transfusions to maintain a level of Hb thought to be high enough for recovery of organ function, but RBC transfusion itself can cause inflammation, organ failure, and death. The safest strategy to optimize RBC transfusion for children supported by ECMO remains a critical knowledge gap. This study is designed to assess the optimal RBC transfusion strategy to reduce organ dysfunction in critically ill children and to ensure that later neurodevelopmental and health-related quality of life outcomes of survivors are preserved. Objectives: The goal of this study is to determine, in children receiving ECMO, whether an approach that provides RBC transfusion for poor tissue oxygen delivery to tissues (Group 1), compared to an RBC transfusion strategy that is based only on hemoglobin level (Group 2), can reduce organ dysfunction and death and improve functioning in survivors. A total of 228 infants and children will be randomly assigned to the two different RBC transfusion strategies (114 per group). The study outcomes include change in organ dysfunction from the start to end of ECMO support, as well as 12-month neurodevelopmental status of survivors. The trial will be conducted in 18 large pediatric ECMO centers, led by an experienced, multidisciplinary clinical trial leadership group. Relevance to Topic Areas: Based on the study population, the proposed study will include many topic areas targeted by Department of Defense (DOD) for research: (1) Congenital Heart Disease (CHD): CHD refers to a number of malformations of the heart present from birth in almost 1% of the population. These children require surgery to correct the defect. Congenital cardiac surgical programs performing these specialized operations use ECMO to rescue patients when they encounter postoperative heart failure. Many of the ECMO patients to be enrolled in the proposed study will have CHD. (2) Cardiomyopathy: Cardiomyopathy is a rare form of heart disease that presents with severe heart failure requiring mechanical heart support with devices such as ECMO for survival or to get patients to transplantation. (3) Emerging Viral Pathogens: ECMO has been invaluable in the support of children and adults with viral heart and lung failure as evidenced in the 2009–2010 H1N1 Influenza and 2019 COVID-19 pandemics. (4) Pathogen-Inactivated Blood Products: Identifying the best approach to maintaining oxygen-carrying hemoglobin via RBC transfusion, a pathogen-inactivated blood product, is the primary goal of this study. In addition, utilization of limited resources, including blood product transfusion volumes, will be assessed as outcomes. (5) Hemorrhage Control will additionally be addressed in the proposed study, as we document the effects of indication-based RBC transfusion on clinical outcomes of bleeding, thrombosis (blood clots), and organ dysfunction. Applicability and Impact: The results of this study will be immediately applicable to the care of more than 3,300 critically ill children supported annually with ECMO in 492 centers across the world. Results will inform RBC transfusion strategies and practice for other critically ill children, including military children undergoing cardiac surgery. In addition, successful completion of the proposed study will inform future clinical tri
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210301
Entities
People
- Lynn A Sleeper
Organizations
- United States Army