Multi-center, randomized, controlled trial of the feasibility and safety of inhaled hydrogen gas during ECPR

ECPR期间吸入氢气可行性和安全性的多中心、随机、对照试验

• 批准号: 10501177
• 负责人: John Nagi Kheir
• 金额: $ 41.06万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10501177
• 关键词: Adult; Adverse effects; Agreement; Area; Biological Markers; Blinded; Blood flow; Boston; Brain; Brain Death; Brain Injuries; Cannulas; Cardiopulmonary Bypass; Cardiopulmonary Resuscitation; Caring; Cellular Structures; Cephalic; Chemicals; Clinical; Clinical Trials; Clinical Trials Data Monitoring Committees; Creatinine; Critical Care; Data; Data Analyses; Devices; Diatoms; Disease; Documentation; Education; Emergency Situation; Enrollment; Ensure; Environment; Family suidae; Feedback; Foundations; Functional disorder; Gases; Goals; Graft Rejection; Heart Arrest; Hepatic; Hour; Hydrogen; Hypoxemia; Image; Impairment; Informed Consent; Infrastructure; Inhalation; Injury; Injury to Kidney; Institutional Review Boards; Interruption; Investigation; Ischemia; Ischemic Stroke; Lead; Logistics; Magnetic Resonance Imaging; Manuals; Measures; Mediator of activation protein; Modeling; Myocardial Infarction; Myocarditis; Nature; Nervous System Physiology; Nervous System Trauma; Neurologic; Nose; Organ Transplantation; Outpatients; Oxygen; Participant; Pathology; Patients; Pediatric Hospitals; Phase; Phase 0 Trial; Pilot Projects; Play; Population; Process; Protocols documentation; Randomized; Randomized Controlled Trials; Recording of previous events; Regulation; Renal function; Reperfusion Injury; Reperfusion Therapy; Reporting; Research; Research Design; Research Personnel; Resuscitation; Rodent; Role; Safety; Seizures; Sepsis; Serious Adverse Event; Serum; Site; Specific qualifier value; Stroke; Symptoms; Testing; Texas; Therapeutic Agents; Time; Translational Research; Work; adjudicate; adjudication; cell injury; clinically significant; community consultation; comorbidity; congenital heart disorder; deprivation; efficacy study; empowered; experience; feasibility testing; functional status; heart function; improved; improved outcome; inclusion criteria; ischemic injury; mechanical circulatory support; meetings; open label; operation; phase 3 study; point of care; pre-clinical; primary endpoint; pulmonary function; randomized trial; recruit; safety and feasibility; safety study; secondary endpoint; severe injury; treatment as usual; treatment group; trial design; white matter injury

Project Summary/Abstract Background. The purpose of the proposed research is to test the feasibility and safety of inhaled hydrogen gas (H2) administration as a rescue therapy during cardiac arrest requiring extracorporeal cardiopulmonary resuscitation (ECPR). Among patients with congenital heart disease (CHD) receiving ECPR, 52% either die or suffer severe neurologic impairment. Diatomic hydrogen (H2) chemically reduces toxic oxygen mediators that directly damage cellular structures, and has been shown to improve neurologic and renal function in a number of preclinical ischemic injury models. Recently, we have demonstrated that inhalation of 2.4% H2 for up to 72 hours is safe in healthy adults. However, H2 has never been applied to the ECPR population. Study design. We propose an early-phase, two-site, randomized trial of H2 in ECPR patients entitled the ‘Hydrogen FAST Trial’ (Hydrogen’s Feasibility And Safety as a Therapeutic agent). Key Inclusion criteria are (1) patients with CHD (broadly defined, including myocarditis, channelopathies, transplant rejection), (2) experiencing a cardiac arrest >5 minutes and receiving ongoing CPR, and (3) a decision made to resuscitate using ECPR. The trial will be led by MPIs John Kheir, MD and Lynn Sleeper, ScD, who have a strong collaborative history in this area and complementary expertise in critical care, translational research, and clinical trials. Furthermore, the trial design has received favorable feedback from the FDA. During the R61 Phase: (1) Regulatory (IRB and FDA) approvals will be obtained, including exception from informed consent (EFIC) requirements. This is necessary because the emergent nature of ECPR and time- sensitivity of H2 preclude traditional informed consent. Instead, non-opt-out patients will be randomized and enrolled emergently, with subsequent traditional informed consent. (2) Investigational product (IP) manufacturing, storage, and administration logistics will be established. (3) Endpoint adjudication processes and DSMB infrastructure will be established. (4) Study roll-out and clinical staff education will be completed, followed by a 3-patient vanguard phase (Phase 0) trial. During the R33 Phase, 53 patients with CHD will be randomly assigned in a 3:2 (32/21) ratio to either usual care plus 2.4% H2 gas following ECPR for 72 hours or to usual care from two sites. Primary endpoints include measures of feasibility and safety (rate of treatment-associated severe adverse events, adjudicated by an independent committee blinded to treatment group). Secondary endpoints will include functional status, brain biomarkers and cranial images obtained using a new point-of-care MRI device. Impact. The experienced team and infrastructure in place for this trial will ensure the successful completion of R31 and R466 milestones. If H2 therapy is shown to be feasible and safe, this work will provide a foundation for H2 administration in the critical care environment, and subsequent testing in cardiac arrest, stroke, myocardial infarction, and other disorders in which ischemia-reperfusion injury plays a role.

项目总结/文摘