HydrogenFAST: Hydrogen's Safety and Efficacy as a Therapy in ECPR
Study Details
Study Description
Brief Summary
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 2.4% hydrogen in gases administered via the ventilator and ECMO membrane for 72 hours.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
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). Each year, 500,000 patients in the US suffer a cardiac arrest and a growing number of them are resuscitated using ECPR. However, neurologic and renal injury remain important resulting comorbidities. The pathophysiology of these often-devastating injuries is ischemia (inadequacy of blood flow, at times compounded by hypoxemia) followed by an abrupt reperfusion (ECMO flow initiation). Among patients with congenital heart disease (CHD) receiving ECPR, 52% either die prior to discharge or suffer severe neurologic impairment. Diatomic hydrogen (H2) administration during and following ECPR may chemically reduce the toxic mediators that directly damage cellular structures and improve neurologically intact survival.
Preclinical data. Several groups have described that H2 inhalation decreases injury when administered following ischemic stroke, myocardial infarction, and cardiac arrest in rodents. Our group demonstrated that inhalation of 2.4% H2 for 24 hours following an experimental swine ischemia-reperfusion injury (as occurs in ECPR) improved neurologic scores, decreased seizures, diminished T2 white matter injury volume by 65%, and improved serum creatinine. Safety study in healthy participants. Under an investigator-initiated IND, we exposed 8 healthy adult participants to up to 72 hours of 2.4% H2 inhalation via high flow nasal cannula, finding no adverse effects on markers of hepatic, renal, cardiac or pulmonary function and no clinically significant symptoms reported. Having received a favorable pre-IND review from the FDA, we propose a two-center early phase study of H2 administration in patients with CHD receiving ECPR.
Study overview. We propose an early-phase randomized trial entitled the 'Hydrogen FAST Trial' (Hydrogen's Feasibility And Safety as a Therapeutic agent). The trial will have a 3-patient vanguard phase and 53 patients with CHD experiencing ECPR randomly assigned in a 3:2 (32/21) ratio to either usual care plus 2.4% H2 gas for 72 hours or to usual care. Patients will be recruited from two sites, Boston Children's Hospital and Texas Children's Hospital. We will primarily examine feasibility and safety (severe adverse events, independently adjudicated), as well as some indicators of efficacy.
Hypotheses. Feasibility endpoint: We hypothesize that H2 gas will be administered for >90% of the first 72 post-arrest hours in patients so-assigned and will be environmentally safe. Safety endpoint: We hypothesize that compared with patients receiving usual post-arrest care, patients receiving H2 will not exceed the treatment-related SAE rate of the usual care group by >12.5% in the 30 days following randomization.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Usual care + H2 therapy Hydrogen administered via mechanical ventilator and sweep gas into ECMO membrane for 72 hours |
Drug: Hydrogen
Hydrogen gas (2.4%) in air or oxygen administered for 72 hours via ventilator and ECMO membrane. Oxygen concentration titrated per clinical team.
Other Names:
Other: Usual care
Usual care post-ECPR event, including targeted temperature management.
Other Names:
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| Active Comparator: Usual care The current standard of care. |
Other: Usual care
Usual care post-ECPR event, including targeted temperature management.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Feasibility of hydrogen administration [72 hours]
Percentage of the first 72 post-randomization hours (starting at the time of randomization) in which H2 gas was administered via all of the applicable pathways (e.g. mechanical ventilator and ECMO membrane).
- Safety of hydrogen administration [30 days]
Incidence rate of SAEs of interest per day during the first 30 days post-randomization that have been classified as treatment-related or possibly treatment-related.
Secondary Outcome Measures
- Survival to hospital discharge [From date of randomization until the date of hospital discharge or date of death from any cause, whichever came first, assessed up to 12 months]
Survival to hospital discharge
- ICU length of stay [From date of randomization until the date of first ICU discharge or date of death from any cause, whichever came first, assessed up to 12 months]
Duration of ICU stay until first transfer out of ICU
- Hospital length of stay [From date of randomization until the date of hospital discharge or date of death from any cause, whichever came first, assessed up to 12 months]
Duration of hospital stay until first hospital discharge
- Functional status score [Calculated on admission to the hospital, at 24 h before cardiac arrest, at hospital discharge, and at 6 months post-randomization]
Functional status score computed based on a detailed review of neurology notes, primary team notes, nursing notes and physical exam documentation by two independent investigators.
Eligibility Criteria
Criteria
INCLUSION CRITERIA
In order to be eligible to participate in this study, an individual must meet all of the following criteria:
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Patients with congenital heart disease, which will be broadly defined, including myocarditis, channelopathies, transplant rejection.
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Patient experiencing a cardiac arrest >5 minutes and receiving ongoing CPR in a cardiac intensive care unit at either Boston Children's Hospital or Texas Children's Hospital.
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The decision made to resuscitate using ECPR.
EXCLUSION CRITERIA
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Enrollment in the opt-out program.
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Randomization is not expected to occur within 2 hours of the decision to resuscitate using ECPR. (This is to exclude patients who are not randomized within 2 hours of ECPR.)
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Boston Children's Hospital
- Baylor College of Medicine
Investigators
- Principal Investigator: John N Kheir, MD, Associate Professor of Pediatrics, Harvard Medical School
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IRB-P00043374