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

Trials. 2017 Oct 23;18(1):488. doi: 10.1186/s13063-017-2246-3.

Abstract

Background: Hydrogen gas inhalation (HI) improved survival and neurological outcomes in an animal model of post-cardiac arrest syndrome (PCAS). The feasibility and safety of HI for patients with PCAS was confirmed in a pilot study. The objective of this study is to evaluate the efficacy of HI for patients with PCAS.

Methods/design: The efficacy of inhaled HYdrogen on neurological outcome following BRain Ischemia During post-cardiac arrest care (HYBRID II) trial is an investigator-initiated, randomized, double-blind, placebo-controlled trial designed to enroll 360 adult comatose (Glasgow Coma Scale score < 8) patients who will be resuscitated following an out-of-hospital cardiac arrest of a presumed cardiac cause. The patients will be randomized (1:1) to either the HI or control group. Patients in the HI group will inhale 2% hydrogen with 24% to 50% oxygen, and those in the control group will inhale 24% to 50% oxygen for 18 h after admission via mechanical ventilation. Multidisciplinary post-arrest care, including targeted temperature management (TTM) between 33 °C and 36 °C, will be provided in accordance with the latest guidelines. The primary outcome of interest is the 90-day neurological outcome, as evaluated using the Cerebral Performance Categories scale (CPC). The secondary outcomes of interest are the 90-day survival rate and other neurological outcomes. This study will provide 80% power to detect a 15% change in the proportion of patients with good neurological outcomes (CPCs of 1 and 2), from 50% to 65%, with an overall significance level of 0.05.

Discussion: The first multicenter randomized trial is underway to confirm the efficacy of HI on neurological outcomes in comatose out-of-hospital cardiac arrest survivors. Our study has the potential to address HI as an appealing and innovative therapeutic strategy for PCAS in combination with TTM.

Trials registration: University Hospital Medical Information Network (UMIN), 000019820 . Registered on 17 November 2015.

Keywords: Out-of-hospital cardiac arrest; hydrogen gas inhalation; post-cardiac arrest syndrome.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Inhalation
  • Adult
  • Aged
  • Aged, 80 and over
  • Brain Ischemia / diagnosis
  • Brain Ischemia / mortality
  • Brain Ischemia / physiopathology
  • Brain Ischemia / therapy*
  • Clinical Protocols
  • Combined Modality Therapy
  • Double-Blind Method
  • Female
  • Glasgow Coma Scale
  • Humans
  • Hydrogen / administration & dosage*
  • Hydrogen / adverse effects
  • Japan
  • Male
  • Middle Aged
  • Neurologic Examination
  • Out-of-Hospital Cardiac Arrest / diagnosis
  • Out-of-Hospital Cardiac Arrest / mortality
  • Out-of-Hospital Cardiac Arrest / physiopathology
  • Out-of-Hospital Cardiac Arrest / therapy*
  • Recovery of Function
  • Research Design
  • Respiration, Artificial* / adverse effects
  • Respiration, Artificial* / mortality
  • Resuscitation* / adverse effects
  • Resuscitation* / mortality
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Hydrogen