Efficacy of inhaled HYdrogen on neurological outcome following BRain Ischemia During post-cardiac arrest care (HYBRID II trial): study protocol for a randomized controlled trial.

Abstract

This paper describes the protocol for the HYBRID II trial, a multicenter, double-blind, placebo-controlled randomized study enrolling 360 comatose adults (Glasgow Coma Scale score below 8) resuscitated after out-of-hospital cardiac arrest of presumed cardiac origin. Participants are allocated 1:1 to receive either 2% hydrogen gas combined with 24–50% oxygen, or oxygen alone, delivered via mechanical ventilation for 18 hours post-admission. All patients also receive multidisciplinary post-arrest care including targeted temperature management at 33–36°C. The primary endpoint is 90-day neurological outcome assessed by the Cerebral Performance Categories scale. Secondary endpoints include 90-day survival and additional neurological measures. The trial is powered at 80% to detect a 15-percentage-point improvement in favorable neurological outcomes (CPC 1–2), from 50% to 65%, at a significance level of 0.05. Prior animal and pilot human data supported the feasibility and safety of this approach.

Mechanism

Hydrogen gas is proposed to selectively scavenge reactive oxygen species, particularly hydroxyl radicals, thereby reducing cerebral ischemia-reperfusion injury occurring after cardiac arrest and resuscitation.