Hydrogen’s Feasibility and Safety as a Therapy in Extracorporeal Cardiopulmonary Resuscitation (Hydrogen‑FAST): study protocol for a trial of inhaled hydrogen gas as an adjunctive therapy in refractory cardiac arrest

Abstract

Background: Extracorporeal cardiopulmonary resuscitation (ECPR) improves survival for patients experiencing refractory cardiac arrest but is often associated with severe ischemia-reperfusion injury (IRI). Hydrogen gas (H2) has demonstrated promising preclinical efficacy in reducing IRI. The Hydrogen-FAST trial investigates the feasibility and safety of inhaled hydrogen gas as an adjunctive therapy during ECPR in patients with congenital heart disease (CHD). Methods: This phase 1 multicenter randomized controlled trial enrols patients of any age undergoing ECPR due to refractory cardiac arrest associated with underlying cardiac morbidity. Due to the emergent nature of ECPR events, the trial leverages an Exception from Informed Consent enrolment process. Fifty-three participants will be randomized to standard care or standard care plus inhaled 2% H2 gas delivered continuously for 72 h via mechanical ventilator and extracorporeal membrane oxygenation (ECMO) circuit. Primary endpoints include feasibility, measured as the percentage of the first 72 h post-arrest in which hydrogen is successfully administered, with feasibility defined as a mean percentage of ≥90%, and safety, evaluated through incidence rates of treatment-related serious adverse events (SAEs). Secondary endpoints examine clinical outcomes including survival to discharge, ICU length of stay, functional status at 6 months, neurologic function, and markers of ischemic injury. Discussion: The Hydrogen-FAST trial will provide essential data on the feasibility and safety of H2 administration during ECPR, informing larger efficacy studies and potential broader clinical use in critical care settings.

Study details

Article type

Original Research

Disease / injury model

Cardiac arrest with resuscitation using extracorporeal cardiopulmonary resuscitation (ECPR)

Duration

30 days

Dose-dependent effect

No

Outcome

Neutral

Findings

This phase 1 multicenter randomized controlled trial will assess the feasibility and safety of inhaled 2% hydrogen gas as an adjunctive therapy during ECPR in patients with congenital heart disease. The primary endpoints are feasibility (mean percentage of 72 hours post-arrest with successful hydrogen administration ≥90%) and safety (incidence of treatment-related serious adverse events). Secondary endpoints include survival to discharge, ICU/hospital length of stay, functional status at 6 months, neurologic function, and markers of ischemic injury. The trial will provide essential data to inform larger efficacy studies and potential broader clinical use in critical care settings.