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

Abstract

IntroductionTo date, there are no randomised, 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. MethodsThis prospective trial was carried out at Barts Heart Centre, UK, employing a randomized, double-blinded, placebo-controlled design. Twenty patients with PersAF (duration <2years) 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. ResultsDuring 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=0.07 and repeat procedure 70% vs 40%;p=0.4). 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. ConclusionThis feasibility study establishes the potential for conducting a blinded, placebo-controlled trial to evaluate the efficacy of PVI versus DCCV in patients with PersAF.