Feasibility of double-blinded, placebo-controlled interventional study for assessing catheter ablation efficacy in persistent atrial fibrillation: Insights from the ORBITA AF feasibility study

Background To date, there are no randomized, double-blinded clinical trials comparing catheter ablation to DC cardioversion (DCCV) with medical therapy in patients with persistent atrial fibrillation (PersAF). Conducting a large-scale trial to address this question presents considerable challenges, including recruitment, blinding, and implementation. We conducted a pilot study to evaluate the feasibility of conducting a definitive placebo-controlled trial. Methods This prospective trial was carried out at Barts Heart Centre, United Kingdom, employing a randomized, double-blinded, placebo-controlled design. Twenty patients with PersAF (duration < 2 years) were recruited, representing 10% of the proposed larger trial as determined by a power calculation. The patients were randomized in a 1:1 ratio to receive either PVI +/- DCCV (PVI group) or DCCV + Placebo (DCCV group). The primary endpoint of this feasibility study was to evaluate patient blinding. Patients remained unaware of their treatment allocation until end of study. Results During the study, 35% of patients experienced recurrence of PersAF prior to completion of 12 months follow-up. Blinding was successfully maintained amongst both patients and medical staff. The DCCV group had a trend to higher recurrence and repeat procedure rate compared to the PVI group (recurrence of PersAF 60% vs 30%; p = .07 and repeat procedure 70% vs 40%; p = .4). The quality of life experienced by individuals in the PVI group showed improvement, as evidenced by enhanced scores on the AF specific questionnaire (AF PROMS) (3 [ +/- 4] vs 21 [+/- 8]) and SF-12 mental-component raw score (51.4 [+/- 7] vs 43.24 [+/- 15]) in patients who maintained sinus rhythm at 12 months. Conclusion This feasibility study establishes the potential for conducting a blinded, placebo-controlled trial to evaluate the efficacy of PVI versus DCCV in patients with PersAF.