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 enrolls 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 enrollment 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.

Trial registration: ClinicalTrials.gov NCT05574296. Registered on October 6, 2022. https://clinicaltrials.gov/study/NCT05574296 .

Keywords: Congenital heart disease; Extracorporeal cardiopulmonary resuscitation; Feasibility study; Hydrogen gas; Ischemia-reperfusion injury; Randomized controlled trial.

Fig. 1

The process of setting up and enrolling patients in the Hydrogen-FAST trial using Exception from Informed Consent includes six sequential steps. (1) A community consultation plan must be approved by both the FDA and single IRB (sIRB). (2) Following initial approval, a series of community consultation meetings take place with both patients and family members as well as staff. (3) Thereafter, comments and feedback are compiled and reviewed by the sIRB. (4) Following approval, a period of public disclosure takes place, after which enrollment can begin. Steps 1–4 are repeated at each participating center. (5) When an eligible patient is identified, a member of the care team checks the opt-out list to ensure the patient’s absence. (6) When deemed appropriate by the clinical staff (a minority of cases), a pre-enrollment opportunity to object or traditional informed consent may be provided to the LAR. (7) The patient is then randomized and enrolled. (8) When deemed appropriate by the clinical team, the LAR is provided an opportunity to object to ongoing participation by a member of the research team

Fig. 2

A secure and central location is used for storage of the investigational product. A “Do Not Enroll” list is affixed to an adjacent wall that contains a patient sticker for any patient who has opted out or who is known to fulfill an exclusion criterion. Two sets of hydrogen tanks (one primary, including a manifold, and one secondary) are each affixed to a cart for ease of transport. The primary cart contains randomization envelopes for on-site randomization by a member of the care team