Efficacy of Hydrogen Inhalation Therapy on Early Recurrence of Atrial Fibrillation Following Catheter Ablation: A Phase II Randomized Controlled Trial

The primary objective is to evaluate the efficacy of hydrogen inhalation therapy regarding the early recurrence of atrial fibrillation and the improvement of quality of life at 3 months following ablation. 5

Secondary objectives include:

• Assessment of hospitalizations and cardioversions during the 3-month blanking period.
• Evaluation of late recurrence of atrial fibrillation up to 12 months post-ablation.
• Measurement of post-operative inflammation markers, specifically white blood cells, interleukin-6, and C-reactive protein.
• Evaluation of the safety of inhaled hydrogen therapy during the perioperative period. 4
• Assessment of treatment acceptability among both patients and caregivers.

The sponsor did not provide information regarding the total number of participants. The study population consists of patients of both genders within the specified age ranges. Participants are diagnosed with atrial fibrillation, specifically presenting as paroxysmal or persistent forms with symptoms of less than 6 months duration. Eligible individuals are candidates for initial ablation via cryoablation or electroporation. Requirements for participation include being over 18 years of age and possessing a smartphone.

This phase II, multicenter, open-label, randomized, controlled trial evaluates the efficacy of inhaled hydrogen therapy on the early recurrence of atrial fibrillation following ablation. The study methodology involves a comparison to assess the impact of a hydrogen and nitrogen gas mixture on clinical outcomes and quality of life. The research includes a screening process to identify eligible candidates, specifically those aged over 18 with paroxysmal or persistent symptoms of less than 6 months who are candidates for first-time procedure. Following enrollment, the primary assessment focuses on the blanking period, defined as 3 months post-procedure, to evaluate the absence of atrial flutter or atrial tachycardia and improvements in the AFEQT score. Secondary endpoints include the frequency of hospitalizations, electrical cardioversion, and changes in inflammation markers such as CRP. The trial duration involves monitoring for late recurrence up to 12 months after the procedure. Adverse events are documented according to CTCAE terminology.

The experimental treatment consists of hydrogen administered as a medicinal gas, compressed. This formulation is a gas mixture composed of 3.6% hydrogen and 96.4% nitrogen. The total volume of 1440 liters is administered via intranasal use.

The primary efficacy endpoint is a binary, composite measure consisting of the absence of early recurrence of atrial fibrillation during the 3-month blanking period—defined as any episode of atrial fibrillation, atrial flutter, or atrial tachycardia lasting at least 30 seconds—combined with an improvement in quality of life. This improvement is quantified by a decrease of at least 5 points in the AFEQT score between day 0 and month 3.

Secondary endpoints include the frequency of hospitalizations, electrical cardioversion, or drug-induced cardioversion during the blanking period, as well as the rate of late recurrence occurring between 3 and 12 months post-ablation. The study will also evaluate changes in the blood concentration of inflammation markers, specifically granulocytes, C-reactive protein, and interleukin-6, comparing levels from 24 hours pre-ablation to 24–48 hours post-ablation. Assessment of treatment acceptance will be conducted using customized questionnaires for both patients and healthcare providers. Safety data will be monitored through the collection of adverse events, which are graded according to the Common Terminology Criteria for Adverse Events.