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

BackgroundHydrogen 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/designThe 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.DiscussionThe 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 registrationUniversity Hospital Medical Information Network (UMIN), 000019820. Registered on 17 November 2015.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-017-2246-3) contains supplementary material, which is available to authorized users.

Hydrogen gas inhalation alleviates oxidative stress in patients with post-cardiac arrest syndrome

“…Due to the small sample size and overall high percentage of favorable outcomes, levels of cytokines were low compared to those in previous reports. (7,44) To further enhance our understanding of this treatment modality, we are currently conducting a large, multicenter, double-blind, randomized control trial in Japan, (45) and the results of this study are expected to reveal the anti-oxidative and anti-inflammatory effect of inhaled H 2 .…”

Hydrogen gas distribution in organs after inhalation: Real-time monitoring of tissue hydrogen concentration in rat

“…Furthermore, it was shown that the inhalation of less than 4% hydrogen is practical and safe for patients 14 . A double-blind, randomised control trials using 2% hydrogen inhalation are ongoing 11,24 . Therefore, we believe that the current results may be applicable to clinical settings.…”

Hydrogen: A Potential New Adjuvant Therapy for COVID-19 Patients

“…Thus, exhaled H 2 diffuses instantly, without accumulating or resulting in an increased concentration exceeding the inspiratory H 2 concentration. Therefore, 2% H 2 gas can be carefully administered in a hospital (Tamura et al, 2017). During this treatment, a very small number of patients have symptoms such as sparse stool, increased defecation frequency, heartburn, and headache after drinking.…”