Hydrogen Therapy for Cardiac Arrest

(HydrogenFAST Trial)

Overseen By Victoria Habet, DO

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Boston Children's Hospital

Disqualifiers: Pregnancy, Prisoners, Prior ECPR, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 72 hours

53 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this project is to test the feasibility and safety of inhaled hydrogen gas (H2) administration as a rescue therapy during cardiac arrest requiring extracorporeal cardiopulmonary resuscitation (ECPR, i.e. mechanical circulatory support). Under exemption from informed consent, patients undergoing refractory cardiac arrest in the cardiac ICU at a participating center will be randomized to standard therapy with or without the administration of 2% hydrogen in gases administered via the ventilator and ECMO membrane for 72 hours.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment Hydrogen Therapy for Cardiac Arrest?

Research shows that inhaling hydrogen gas can improve brain and heart function in animal models of cardiac arrest, and it is safe and feasible for human patients. Additionally, hydrogen-rich saline has been found to protect organs and improve survival and brain function in rats after cardiac arrest. ^{1 2 3 4 5}

How does hydrogen therapy differ from other treatments for cardiac arrest?

Hydrogen therapy is unique because it involves inhaling hydrogen gas, which acts as an antioxidant to protect cells and organs from damage after cardiac arrest. This approach is different from traditional treatments like therapeutic hypothermia, as it directly targets oxidative stress and inflammation. ^{1 2 6 7 8}

Research Team

John N Kheir, MD

Principal Investigator

Associate Professor of Pediatrics, Harvard Medical School

Eligibility Criteria

This trial is for patients from birth to 18 years, and occasionally older, who are experiencing a tough-to-treat cardiac arrest and are being treated with ECPR in the ICU at Boston Children's or Texas Children's Hospital. They may have heart conditions like congenital disease, myocarditis, arrhythmia, or transplant rejection.

Inclusion Criteria

I am in a cardiac ICU at Boston or Texas Children's Hospital for a heart condition.

My clinical team has chosen ECPR for my ongoing cardiac arrest due to no other options.

I am 18 years old or younger, but there might be exceptions if I'm older.

Exclusion Criteria

I was not enrolled in the trial within 2 hours after deciding to use ECPR.

Patients who are prisoners

Prior ECPR episode during admission (whether or not they were enrolled in the trial)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive usual care plus 2% H2 gas for 72 hours or usual care alone

72 hours

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

Long-term follow-up

Participants' ICU and hospital length of stay, survival to hospital discharge, and functional status are assessed

Up to 12 months

Treatment Details

Interventions

• Hydrogen

Trial Overview The study tests if breathing hydrogen gas is safe and doable as an extra treatment during ECPR for cardiac arrest. Patients will either get standard care or standard plus hydrogen gas through their ventilator and ECMO system for three days.

Participant Groups

Group I: Usual care + H2 therapy Experimental Treatment 2 Interventions

Hydrogen administered via mechanical ventilator and sweep gas into ECMO membrane for 72 hours

Group II: Usual care Active Control 1 Intervention

The current standard of care.

Who Is Running the Clinical Trial?

Boston Children's Hospital

Lead Sponsor

Trials

801

Recruited

5,584,000+

Baylor College of Medicine

Collaborator

Trials

1,044

Recruited

6,031,000+

Findings from Research

Inhaled molecular hydrogen (H2) was tested in a trial with 73 patients who suffered out-of-hospital cardiac arrest, showing a promising increase in 90-day survival rates (85% in the H2 group vs. 61% in the control group).

While the primary outcome of improved neurological function was not statistically significant, secondary outcomes indicated that H2 inhalation may lead to better survival rates and fewer neurological deficits, suggesting potential benefits of H2 therapy in post-cardiac arrest care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of inhaled hydrogen on neurological outcome following brain ischaemia during post-cardiac arrest care (HYBRID II): a multi-centre, randomised, double-blind, placebo-controlled trial. Tamura, T., Suzuki, M., Homma, K., et al.[2023]

In a small study of 5 patients who experienced out-of-hospital cardiac arrest, hydrogen gas inhalation (HI) combined with target temperature management (TTM) showed no adverse effects and resulted in 4 patients surviving with favorable neurological outcomes after 90 days.

This suggests that HI is a feasible and potentially beneficial therapy for patients suffering from post-cardiac arrest syndrome (PCAS), marking the first investigation of HI in human subjects with this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility and Safety of Hydrogen Gas Inhalation for Post-Cardiac Arrest Syndrome - First-in-Human Pilot Study. Tamura, T., Hayashida, K., Sano, M., et al.[2017]

The HYBRID II trial is a large-scale study involving 360 adult comatose patients who experienced out-of-hospital cardiac arrest, aiming to evaluate the efficacy of hydrogen gas inhalation (HI) on neurological outcomes after cardiac arrest.

The study will assess the impact of HI on 90-day neurological outcomes and survival rates, with the potential to show that HI, combined with targeted temperature management, could be a promising treatment for improving recovery in patients with post-cardiac arrest syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Tamura, T., Hayashida, K., Sano, M., et al.[2022]

Hydrogen (H2) inhalation started after achieving return of spontaneous circulation (ROSC) significantly improved survival rates and neurological outcomes in a rat model of cardiac arrest, with a survival rate of 85.7% in the group receiving both H2 and targeted temperature management (TTM).

The combination of TTM and H2 inhalation was more effective than TTM alone, leading to better neurological scores and reduced neuronal degeneration, highlighting the potential of H2 inhalation as a therapeutic strategy in post-cardiac arrest care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hydrogen inhalation during normoxic resuscitation improves neurological outcome in a rat model of cardiac arrest independently of targeted temperature management. Hayashida, K., Sano, M., Kamimura, N., et al.[2015]

In a study involving Sprague-Dawley rats, hydrogen-rich saline significantly improved survival rates and neurological outcomes after cardiac arrest and resuscitation, demonstrating its potential as a therapeutic intervention.

The benefits of hydrogen-rich saline were linked to its ability to reduce oxidative stress and inflammation, as well as decrease apoptosis, suggesting a protective mechanism that preserves brain function following cardiac events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hydrogen-rich saline improves survival and neurological outcome after cardiac arrest and cardiopulmonary resuscitation in rats. Huo, TT., Zeng, Y., Liu, XN., et al.[2021]

Inhalation of molecular hydrogen (H2) gas during cardiopulmonary resuscitation (CPR) significantly improved survival rates and neurological outcomes in a rat model of cardiac arrest, showing effects comparable to therapeutic hypothermia.

H2 gas inhalation also prevented harmful increases in left ventricular pressure and inflammatory markers after the return of spontaneous circulation, suggesting its effectiveness as an antioxidant in reducing ischemia-reperfusion injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

H(2) gas improves functional outcome after cardiac arrest to an extent comparable to therapeutic hypothermia in a rat model. Hayashida, K., Sano, M., Kamimura, N., et al.[2021]

Inhalation of hydrogen (H2) gas after cardiac arrest significantly improved survival rates in rabbits, with 15 out of 30 rabbits surviving in the H2 treatment group compared to 7 out of 30 in the control group after 72 hours.

H2 treatment led to quicker recovery of heart rate and reduced levels of cardiac injury markers (like cTnI and BNP) compared to the control group, indicating that H2 helps alleviate cardiac dysfunction and myocardial injury following resuscitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hydrogen can alleviate post-cardiac arrest myocardium injury in rabbits]. Wang, J., Lin, J., Zhang, M., et al.[2019]

Hydrogen has been identified as a significant physiological regulator with protective effects, including antioxidant, anti-inflammatory, and anti-apoptotic properties, which can benefit cells and organs.

Various delivery methods for therapeutic hydrogen, such as inhalation, drinking hydrogen-infused water, and injection of hydrogen-saturated saline, have shown promise in clinical and basic research, suggesting its potential as a major therapeutic strategy in medicine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent advances in hydrogen research as a therapeutic medical gas. Huang, CS., Kawamura, T., Toyoda, Y., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Efficacy of inhaled hydrogen on neurological outcome following brain ischaemia during post-cardiac arrest care (HYBRID II): a multi-centre, randomised, double-blind, placebo-controlled trial. [2023]

2. Japan pubmed.ncbi.nlm.nih.gov

Feasibility and Safety of Hydrogen Gas Inhalation for Post-Cardiac Arrest Syndrome - First-in-Human Pilot Study. [2017]

3. England pubmed.ncbi.nlm.nih.gov

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. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Hydrogen inhalation during normoxic resuscitation improves neurological outcome in a rat model of cardiac arrest independently of targeted temperature management. [2015]

5. United States pubmed.ncbi.nlm.nih.gov

Hydrogen-rich saline improves survival and neurological outcome after cardiac arrest and cardiopulmonary resuscitation in rats. [2021]

6. England pubmed.ncbi.nlm.nih.gov

H(2) gas improves functional outcome after cardiac arrest to an extent comparable to therapeutic hypothermia in a rat model. [2021]

7. China pubmed.ncbi.nlm.nih.gov

[Hydrogen can alleviate post-cardiac arrest myocardium injury in rabbits]. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Recent advances in hydrogen research as a therapeutic medical gas. [2022]