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

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

Tomoyoshi Tamura  1   2 , Kei Hayashida  3   4 , Motoaki Sano  4   5 , Shuko Onuki  4 , Masaru Suzuki  3   4
Affiliations
Randomized Controlled Trial

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

Tomoyoshi Tamura et al. Trials. .

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.

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Conflict of interest statement

Ethics approval and consent to participate

This protocol was approved by the ethics committee of the Keio University School of Medicine (reference number 20150266). Additionally, this trial has been approved as an advanced medicine clinical trial by the Ministry of Health, Labor and Welfare of the Japanese government (reference number 1117-2). Ethics committee approval will be obtained at each participating hospital, and recruitment of patients will not start in those hospitals unless this study is approved by the ethics committee of that hospital. All amendments will be submitted for approval of the ethics committee of the Keio University School of Medicine and the Ministry of Health, Labor and Welfare of the Japanese government. A detailed description of obtaining consent to participate is provided within the text of this article.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Flow diagram of the study design. Patients will be randomly allocated 1:1 to the hydrogen group or the control group using content-blinded cylinders. Trial gas inhalation will be initiated after intensive care unit admission and continued for 18 h. Multidisciplinary treatments, including targeted temperature management, will be performed in all patients according to the latest International Liaison Committee on Resuscitation (ILCOR) guidelines. CPC Cerebral Performance Categories scale, GCS Glasgow Coma Scale, PCAS Post-cardiac arrest syndrome, PEEP Positive end-expiratory pressure, ROSC Return of spontaneous circulation, SpO 2 Peripheral oxygen saturation
Fig. 2
Fig. 2
System of trial gas inhalation. The trial gas will be inhaled through this system. Trial gas will be supplied from a cylinder with constant flow, and it will be mixed with oxygen from the mechanical ventilator (SERVO-s®; MAQUET Critical Care AB) at the inspiratory duct. The cylinder is filled with 4% H2 and 96% nitrogen for the hydrogen group and 100% nitrogen for the control group. A tidal volume and fraction of inspired oxygen meter will be used during trial gas inhalation to monitor ventilation
Fig. 3
Fig. 3
Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) figure depicting schedule of enrollment, interventions, and assessments. † Hemodynamic parameters will be obtained using commercially available systems (PiCCO®, MAQUET Critical Care AB; or EV1000®, Edwards Lifesciences, Irvine, CA, USA). * Perform head CT scan and EEG during the daytime after 72 h from the initiation of intervention. ABG Arterial blood gas analysis, AEs Adverse events, BP Blood pressure, CAG Coronary angiography, CBC Complete blood count, CPC Cerebral Performance Categories scale, CT Computed tomography, ECG Electrocardiogram, EEG Electroencephalogram, ER Emergency room, FiO 2 Fraction of inspired oxygen, GCS Glasgow Coma Scale, HR Heart rate, MMSE Mini Mental State Examination, mRS Modified Rankin Scale, PCI Percutaneous coronary intervention, PEEP Positive end-expiratory pressure, SpO 2 Peripheral oxygen saturation
See this image and copyright information in PMC

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