Hydrogen Therapy for Cardiac Arrest

(HydrogenFAST Trial)

Recruiting at 4 trial locations

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether inhaled hydrogen gas can aid patients during a severe heart crisis called cardiac arrest. Researchers aim to determine if adding hydrogen to the usual treatment enhances safety and effectiveness when using a machine that supports circulation, known as ECPR. The trial compares standard care with and without hydrogen treatment. It seeks patients in a cardiac intensive care unit who have existing heart problems and are experiencing a serious cardiac arrest with ongoing CPR. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

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

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that inhaling hydrogen gas can be safe for people. One study found that breathing in 2.4% hydrogen gas did not cause major side effects in healthy adults, suggesting it is well-tolerated.

Other studies have found that hydrogen gas improved outcomes in animals after cardiac arrest, indicating potential benefits when the heart stops suddenly.

This trial is in its early stages, focusing primarily on ensuring the treatment's safety and lack of harm. Testing at this stage usually indicates some confidence in its safety, but more information is needed for certainty.

Overall, the treatment appears promising, but further research is necessary to confirm its safety for people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cardiac arrest?

Most treatments for cardiac arrest focus on restoring blood flow and oxygenation through techniques like CPR, defibrillation, and advanced life support. However, hydrogen therapy stands out because it introduces hydrogen gas as an active ingredient, administered via a mechanical ventilator and sweep gas into the ECMO membrane. Researchers are excited about this approach because hydrogen has potential antioxidant properties that may protect heart and brain tissues from damage after cardiac arrest. This innovative method could offer a new layer of protection and improve recovery outcomes, setting it apart from traditional treatments.

What evidence suggests that hydrogen therapy might be an effective treatment for cardiac arrest?

This trial will compare the effects of usual care with and without the addition of hydrogen therapy for cardiac arrest recovery. Studies have shown that inhaling hydrogen gas (H2) can enhance recovery after a heart attack. Animal research has demonstrated that inhaling H2 can increase survival rates and improve brain function. Human studies suggest that combining hydrogen therapy with mild cooling treatment results in better brain recovery than cooling alone. Specifically, one study found that inhaling H2 improved heart function after resuscitation by reducing harmful cell activities. These early findings indicate that hydrogen therapy could be promising for aiding recovery after a heart attack. ^{1 4 6 7 8}

Who Is on the Research Team?

John N Kheir, MD

Principal Investigator

Associate Professor of Pediatrics, Harvard Medical School

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10030910/

Efficacy of inhaled hydrogen on neurological outcome ... Inhaled molecular hydrogen gas (H2) has been shown to improve outcomes in animal models of cardiac arrest (CA). H2 inhalation is safe and ...

2. journals.lww.com journals.lww.com/ccmjournal/fulltext/2024/10000/combination_of_hydrogen_inhalation_and_hypothermic.7.aspx

A Post hoc Analysis of the Efficacy of Inhaled Hydrogen ... CONCLUSIONS: Hydrogen + TTM32–TTM34 was associated with improved neurologic outcomes after cardiogenic OHCA compared with TTM32–TTM34 monotherapy. Hydrogen ...

3. ahajournals.org ahajournals.org/doi/10.1161/JAHA.112.003459

H2 Gas Improves Functional Outcome After Cardiac Arrest ... H2 gas inhalation yielded better improvement in survival and neurological deficit score (NDS) after ROSC to an extent comparable to TH. H2 gas ...

4. spandidos-publications.com spandidos-publications.com/10.3892/etm.2022.11302

Hydrogen therapy after resuscitation improves myocardial ... In conclusion, H2 gas inhalation after return of spontaneous circulation improved cardiac function via the inhibition of autophagy. Introduction.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39133068/

A Post hoc Analysis of the Efficacy of Inhaled Hydrogen on ... Conclusions: Hydrogen + TTM32-TTM34 was associated with improved neurologic outcomes after cardiogenic OHCA compared with TTM32-TTM34 ...

6. childrensnational.org childrensnational.org/get-care/departments/cardiac-intensive-care-unit-cicu/hydrogen-fast-study

Hydrogen-FAST Study Unfortunately, fewer than 50% of patients who have a cardiac arrest and are placed on ECMO survive, largely due to the lack of oxygen that occurs during the ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05574296

Hydrogen's Feasibility and Safety as a Therapy in ECPR 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 ...

8. ahajournals.org ahajournals.org/doi/10.1161/circ.144.suppl_2.10368

Abstract 10368: The Safety and Tolerability of Prolonged ... Conclusion: Inhalation of 2.4% H2 gas does not appear to cause clinically significant adverse effects in healthy adults. These data will be ...