The US Food and Drug Administration’s (FDA) Circulatory Systems Devices advisory panel voted against Medtronic’s Phased RF Ablation System, the first atrial fibrillation ablation therapy under investigation for the treatment of persistent and long-standing persistent atrial fibrillation. While the panel unanimously agreed the technology is effective, the majority did not believe there is reasonable assurance of the safety of the ablation system, and that the clinical benefits of the technology do not outweigh the potential risks based on the TTOP-AF clinical trial data.
The committee recommendation, although not binding, will be considered by the FDA as it reviews the pre-market approval application for the Medtronic Phased RF Ablation System. Medtronic submitted a modular pre-market approval application with the last submission completed in June 2011 based on data from its pivotal TTOP-AF (Tailored treatment of persistent atrial fibrillation) clinical trial, the first randomised study comparing ablation therapy to traditional medical management (antiarrhythmic drugs and direct current cardioversion) in patients with persistent or long-standing persistent atrial fibrillation.
“While we are disappointed with this outcome, Medtronic looks forward to continuing discussions with the FDA to determine the best path forward,” said Reggie Groves, vice president and general manager of Medtronic’s AF Solutions business. “We believe this technology would represent an important option for the persistent or long-standing persistent atrial fibrillation population, for whom treatment is limited.”
Currently, the only FDA approved atrial fibrillation ablation medical devices are indicated for the treatment of paroxysmal atrial fibrillation. As the disease progresses into persistent or long-standing persistent atrial fibrillation, it becomes more complex to treat. Persistent atrial fibrillation patients often have increased hospitalisations and healthcare costs, and the condition is more debilitating in terms of quality of life.
Results from the TTOP-AF clinical trial were presented on 10 October at Venice Arrhythmias 2011, the 12th International Workshop on Cardiac Arrhythmias. The study met its chronic effectiveness endpoint, demonstrating that 55.8% of patients treated with the Medtronic Phased RF Ablation System had an atrial fibrillation and atrial flutter burden reduction of greater than 90% and were free from antiarrhythmic drug therapy at six months, compared to 26.4% in the traditional medical management arm (p<0.0001). When including patients still on antiarrhythmic drug therapy following the procedure with the ablation system, 67.4% had a greater than 90% reduction of atrial fibrillation burden at six months.
The acute safety event rate in the trial was 12.3% with an upper 95% confidence interval of 19%, which did not meet the pre-defined performance goal of 16%. At the time the trial was designed, no benchmark for the persistent atrial fibrillation patient population existed, so the performance goal of 16% was established based on a literature review evaluating ablation procedures in paroxysmal atrial fibrillation ablation patients. These specific safety findings were not unexpected since persistent or long-standing persistent atrial fibrillation patients undergoing ablation have a higher risk of adverse events due to the advanced state of the disease and the complexity of the procedure.
The Medtronic Phased RF Ablation System is investigational in the United States and currently approved for use in areas of Europe, Asia, and Africa, as well as in Canada. More than 13,000 patients in 24 countries have been treated with the system since January 2009.
About the Phased RF Ablation System
The Medtronic Phased RF Ablation System is a percutaneous cardiac catheter and generator system that delivers customised radiofrequency (RF) energy designed to eliminate or isolate abnormal electrical impulses in the left atrium (upper left chamber of the heart) that initiate or sustain atrial fibrillation. The anatomically designed, multi-electrode catheters are intended to allow physicians to identify and selectively ablate a broader area of heart tissue without the use of current single point catheters and complex mapping and navigation equipment.