Hydrogen's Feasibility and Safety as a Therapy in ECPR

Cardiac Arrest Clinical Trial

— HydrogenFAST  

Official title:

Hydrogen's Feasibility and Safety as a Therapy in Extracorporeal Cardiopulmonary Resuscitation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05574296
• Other study ID #: IRB-P00043374
• Status: Recruiting
• Phase: Phase 1
• Start date: March 4, 2024
• Est. completion date: August 31, 2027

Study information

• Verified date: March 2024
• Source: Boston Children's Hospital
• Contact: John N Kheir, MD
• Phone: 8576368890
• Email: john.kheir[@]childrens.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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, 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 53
• Est. completion date: August 31, 2027
• Est. primary completion date: March 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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 Boston Children's Hospital or Texas Children's Hospital 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.

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 2 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.

Related Conditions & MeSH terms

• Cardiac Arrest
• Extracorporeal Membrane Oxygenation
• Reperfusion Injury

Intervention

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

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

Locations

Country	Name	City	State
United States	Boston Children's Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Boston Children's Hospital	Baylor College of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Feasibility of hydrogen administration	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).	72 hours
Primary	Safety of hydrogen administration	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.	30 days
Secondary	Survival to hospital discharge	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
Secondary	ICU length of stay	Duration of ICU stay until first transfer out of ICU	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
Secondary	Hospital length of stay	Duration of hospital stay until first 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
Secondary	Functional status score	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.	Calculated on admission to the hospital, at 24 h before cardiac arrest, at hospital discharge, and at 6 months post-randomization