An overview of clinical trials on atrial fibrillation ablation devices seeking FDA approval was presented by Hugh Calkins, Johns Hopkins Hospital, Baltimore, USA, at the Boston AF Symposium (Boston, 14–16 January 2010).
“2009 was a landmark year for the field of AF ablation as the Biosense Navistar Thermocool ablation system was approved by the FDA for AF ablation,” he said.
This year, two trials will compare two investigational devices in the USA to Navistar Thermocool control groups. The IRASE AF study will randomise 324 symptomatic paroxysmal AF patients to receive the St Jude Medical Duo System or the Thermocool catheter. Enrolment will beging in mid 2010. The other trial, the ToccaStar, will compare the TactiCath (Endosense) which was approved in the Europe Union in 2009, to the Thermocool catheter. The study is to be initiated in the first half of 2010.
Calkins told delegates that there are 120 trials involving AF ablation listed on Clinicaltrials.gov. Of these, 83 are catheter ablation trials – 72 involving available ablation technology and 11 involving new technologies. “Twelve are completed, 36 are enrolling, 14 are inactive, four terminated or suspended, and six are pending,” he said. “It is interesting that 49 are hospital-funded trials, 25 funded by industry, and three by the National Heart, Lung and Blood Institute.”
The Cryo-Cath Arctic Front trial has completed follow-up and the data is being analysed for FDA review. The Ablation Frontiers trial of continuous AF ablation has completed enrolment and is in the follow-up phase. The CardioFocus ablation trial has entered a new feasibility phase.
Cardiac Rhythm News does a round up on the main trials reviewed by Calkins.
Studies seeking FDA approval
Navistar Thermocool Trial
Sponsor: Biosense Webster.
This randomised (2:1), unblended, controlled trial enrolled symptomatic, paroxysmal AF patients, refractory to at least one anti-arrhythmic drug. The study targeted up to 30 sites enrolling a maximum of 230 subjects. The Navistar Thermocool catheter was approved by the FDA for AF indication on 6 February 2009.
Biosense Webster also sponsors a Post Approval Registry to demonstrate that AF ablation with ThermoCool is safe when performed by less experienced operators. The registry also aims to demonstrate long-term safety and effectiveness of the device. It is a prospective, multicentre, non-randomised post approval evaluation of two registry arms that include physicians with different levels of AF ablation experience. Patients will be followed for five years. Primary endpoint is seven-day major complication rate. Secondary endpoint is long-term recurrence of symptomatic AF and long-term complication rate.
STOP-AF Pivotal Trial (Arctic Front Cardiac Cryoablation Catheter and Cryoconsole with the Freezor Max Cardiac Cryoablation Catheter)
Sponsor: Medtronic Cryocath
This randomised, controlled, multicentre trial will compare in a 2:1 ratio the Cryoablation catheter to an approved anti-arrhythmic drug arm. The anti-arrhythmic drug group will be allowed to crossover to cryoablation after six months. The trial enrolled 245 patients to be followed for 12 months. Patients with paroxysmal AF, who failed one or more anti-arrhythmic drugs (flecainide, propafenone, sotalol), with two episodes per month in two months prior to ablation, one episode documented with a tracing, and left appendage 5cm or smaller were included. The study excluded patients with persistent and chronic AF, patients who used amiodarone six months prior to ablation, had cardioversion three months prior to ablation, or two cardioversions in two years prior to ablation.
The study started in October 2006, and enrolment was completed in 2008. Twelve-month follow-up was completed in July 2009. Data analysis is underway for FDA submission.
TTOP-AF (Tailored treatment of permanent AF trial)
Sponsor: Medtronic Ablation Frontiers
This open label, multicentre trial randomised 210 patients to ablation with the Ablation Frontiers RF Ablation System or medical management (2:1). Patients are between 18 and 70 years old, with symptomatic persistent or permanent AF, and one failed class I or III anti-arrhythmic drug. Enrolment in the pivotal trial completed in May 2009. Study follow-up completion is scheduled for June 2010.
Endoscopic Ablation System
This is a prospective, multicentre feasibility trial for patients with paroxysmal AF. The study included 100 patients (18–70 years) at 10 sites to be followed for 12 months.
IRASE AF Study (Irrigated ablation system evaluation for AF)
Sponsor: St Jude Medical
This randomised, open-label, multicentre trial will compare ablation with the St Jude Medical Duo System to an active control group (Thermocool catheter). It involves 324 symptomatic paroxysmal AF patients, aged >18 years, with one failed class I or III anti-arrhythmic drug. In
the safety and efficacy study design, patients will followed by for 12 months (including three month blanking period). Primary endpoint is freedom from symptomatic AF. Conditional approval received from FDA. Enrolment will start mid-2010.
ToccaStar Trial of the TactiCath Ablation Catheter (Proposed IDE study design)
This prospective, randomised, multicentre study will compare the TactiCath catheter to the Biosense Thermocool catheter in patients with symptomatic paroxysmal AF, who failed one class I–IV anti-arrhythmic drug. Effectiveness will be assessed by acute and chronic success, and incidence of procedure related serious adverse events. The study is to be initiated in the first half of 2010.
Magellan Study of the Bard HD Mesh ablator diagnostic and ablation catheter
Sponsor: CR Bard
This study is a prospective, randomised, controlled, multicentre trial comparing the HD Mesh ablator to medical therapy. The trial included 279 paroxysmal AF patients (21–75 years old) at 30 sites. The study will follow patients for 12 months, with a blanking period of 90 days. Anti-arrhythmic drug patients who have AF recurrence after completion of the blanking period may crossover to the ablation arm. Study enrolment started in 2009. The trial has been suspended with plans to restart once modifications are made to the ablation catheter.