Hydrogen's Feasibility and Safety as a Therapy in ECPR

NCT ID: NCT05574296

Last Updated: 2025-07-03

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 53 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-04
• Study Completion Date: 2027-08-31

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% hydrogen in gases administered via the ventilator and ECMO membrane for 72 hours.

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% H2 gas for 72 hours or to usual care. Patients will be recruited from two sites. We will primarily examine feasibility and safety (severe adverse events, independently adjudicated), as well as some indicators of efficacy.

Hypotheses. Primary feasibility endpoint: We hypothesize that H2 gas will be administered for a mean of >90% of the first 72 consecutive post-arrest hours in patients so-assigned. Primary 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. Secondary feasibility endpoint: We hypothesize that H2 gas will be administered for a mean of >90% of the first 72 consecutive hours post-H2 initiation in patients so-assigned.

Conditions

Cardiac Arrest; Extracorporeal Membrane Oxygenation; Reperfusion Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Usual care + H2 therapy

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

Group Type: EXPERIMENTAL

Hydrogen

Intervention Type: DRUG

Hydrogen gas (2%) in air or oxygen administered for 72 hours via ventilator and ECMO membrane. Oxygen concentration titrated per clinical team.

Usual care

Intervention Type: OTHER

Usual care post-ECPR event, including targeted temperature management.

Usual care

The current standard of care.

Group Type: ACTIVE_COMPARATOR

Usual care

Intervention Type: OTHER

Usual care post-ECPR event, including targeted temperature management.

Interventions

Hydrogen

Hydrogen gas (2%) in air or oxygen administered for 72 hours via ventilator and ECMO membrane. Oxygen concentration titrated per clinical team.

Intervention Type: DRUG

Usual care

Usual care post-ECPR event, including targeted temperature management.

Intervention Type: OTHER

Other Intervention Names

H2 gas; Standard of care

Eligibility Criteria

Inclusion Criteria

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. Patients admitted to a cardiac intensive care unit at a participating site with cardiac comorbidity, including congenital heart disease, myocarditis, cardiac arrhythmia, or rejection of a transplanted heart.

2. Patients are anticipated to be between birth to 18 years of age, although occasionally a patient over the age of 18 may be enrolled.

3. Patient experiencing a refractory cardiac arrest >5 minutes and receiving ongoing CPR in the ICU, cardiac catheterization lab, or cardiac operating room.

4. The decision made by the clinical team to resuscitate from ongoing, refractory cardiac arrest using ECPR due to a lack of other available options.

Exclusion Criteria

Meeting any of the following criterion renders the patient ineligible for the trial:

1. Enrollment in the opt-out program.

2. Patients known to be pregnant.

3. Patients who are prisoners.

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

5. Enrollment does not occur within 6 hours of the decision to resuscitate using ECPR.

Note that ECMO cannulation without preceding CPR does not qualify as ECPR and such patients will not be included.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boston Children's Hospital

OTHER

Sponsor Role: lead

Responsible Party

John Kheir

Associate Professor of Pediatrics, Harvard Medical School

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

John N Kheir, MD

Role: PRINCIPAL_INVESTIGATOR

Associate Professor of Pediatrics, Harvard Medical School

Locations

Children's National Hospital

Washington D.C., District of Columbia, United States

Site Status: NOT_YET_RECRUITING

Boston Children's Hospital

Boston, Massachusetts, United States

Site Status: RECRUITING

Children's Mercy Kansas City

Kansas City, Missouri, United States

Site Status: NOT_YET_RECRUITING

Primary Children's Hospital

Salt Lake City, Utah, United States

Site Status: NOT_YET_RECRUITING

Countries

United States

Central Contacts

John N Kheir, MD

Role: CONTACT

john.kheir@childrens.harvard.edu

8576368890

Victoria Habet, DO

Role: CONTACT

Facility Contacts

Bao (Robyn) Nguyen Puente, MD

Role: primary

bpuente@childrensnational.org

John Kheir, MD

Role: primary

john.kheir@childrens.harvard.edu

8576368890

Niranjan Vijayakumar, MBBS

Role: primary

nvijayakumar1@cmh.edu

Stephanie Goldstein, MD

Role: primary

stephanie.goldstein@hsc.utah.edu

Other Identifiers

IRB-P00043374

Identifier Type: -

Identifier Source: org_study_id