February 9, 2009 - Biosense Webster Inc. said Friday the FDA granted market clearance for the NaviStar ThermoCool Catheter for the treatment of drug refractory recurrent symptomatic paroxysmal atrial fibrillation, when used with compatible 3D electroanatomic mapping systems.
The FDA clearance is the first for an ablation system to treat atrial fibrillation, or AFib, in the U.S. AFib is a highly prevalent heart rhythm disorder affecting about 10 million people worldwide, and one of the most common causes of stroke. Cardiologists already treat simpler forms of arrhythmias with catheter ablation such as Wolff-Parkison-White Syndrome, Type I atrial flutter and atrioventricular nodal re-entry tachycardia (AVNRT).
The company said conditions of approval include a post-marketing registry and a physician education program about use of the product. The approval is based on results from a multicenter study comparing catheter ablation to drug therapy for the treatment of AFib. In this randomized clinical trial, catheter ablation was shown to significantly outperform anti-arrhythmic drug (AAD) therapy for the treatment of drug refractory recurrent symptomatic paroxysmal AFib. These data were first presented in November 2008 at the American Heart Association’s Annual Scientific Sessions.
The NaviStar ThermoCool Catheter is also approved in the U.S. for the treatment of Type 1 atrial flutter and recurrent drug/device refractory sustained monomorphic ventricular tachycardia due to prior myocardial infarction.
The FDA approval last week also includes the EZ Steer ThermoCool Navigational Catheter, which is a bi-directional version of the catheter. These catheters are compatible with 3D mapping systems that recognize the Carto System magnetic location sensors.
According to data from the clinical trials, patients receiving cardiac ablation with the NaviStar ThermoCool Catheter were significantly more likely to be free of recurring AF and experienced fewer serious adverse events than those receiving AAD therapy.
This clinical trial was a randomized, unblinded and controlled evaluation of symptomatic, paroxysmal AFib patients who were refractory to at least one AAD and had at least three episodes of AFib in the six months prior to randomization. A total of 167 patients were enrolled from 19 sites throughout the world and the primary effectiveness endpoint (chronic success) was freedom from documented symptomatic AFib recurrence following procedural endpoint confirmation and absent new AAD use or repeat ablation outside of protocol-defined criteria.
The probability of chronic success was 62.7 percent for patients receiving NaviStar ThermoCool Catheter ablation at end of the nine-month effectiveness evaluation period, which is significantly superior to the 17.2 percent probability for the group of patients treated with AAD. The NaviStar ThermoCool Catheter ablation group also demonstrated a dramatic reduction in symptomatic AFib recurrence compared with patients treated with AAD (75 vs. 21 percent).
Additionally, the catheter ablation group demonstrated an excellent safety profile with no device-related serious adverse events such as death, heart attack, stroke, cerebrovascular accident, heart block or atrial perforation within seven days post ablation. Importantly, there was no clinically significant pulmonary vein stenosis in patients receiving ablation, and the incidence of serious adverse events in the NaviStar ThermoCool Catheter group in the 90 days following initiation of therapy was observed to be approximately half that in the AAD group (35.1 vs. 18.4 percent). Biosense Webster sponsored this trial.
“The results are consistent with clinical experience,” said David Wilber, M.D., principal investigator of the study and a professor of cardiovascular science and director, division of cardiology, Loyola University Medical Center in Maywood, IL. “There have been a few other small trials that have been conducted in patients with paroxysmal AFib, which showed a similar advantage. Those trials were done with a variety of different tools, a variety of definitions of endpoints…this was probably the largest multicenter study. I think the results are encouraging because it was over a wide range of centers and had very good results.”
Dr. Wilber believes the NaviStar ThermoCool is a safe system due to its continuous irrigation feature.
“By providing continuous irrigation and cooling of the catheter tip, it helps prevent overheating of the endothelium immediately underneath the ablation catheter,” Dr. Wilber said. “This reduces the risk of charring and thrombus formation during radiofrequency energy application, and the risk of stroke and other thromboembolic events.”
As a result of the trial, the Circulatory System Devices Panel of the FDA unanimously recommended approval of Biosense Webster’s pre-market approval supplement for the NaviStar ThermoCool Catheter for the treatment of symptomatic paroxysmal AFib.
“Probably the most important part of that trial was it was one of the first times where there was regulatory approval based on that data,” said Gerald Naccarelli, M.D., professor of medicine, Penn State College of Medicine, chief, division of cardiology, Penn State Milton S. Hershey Medical Center. “We’ve been using catheters and systems approved for mapping and diagnostics and ablation of atrial flutter and other things. Through some of this data, we’re completing the loop of commercial approval.”
According to clinicians, more data is needed to understand the short- and long-term outcomes of catheter ablation for the treating AFib.
“What we don’t have are prospective randomized trials,” Dr. Naccarelli said. “[There is] very little data comparing it against anti-arrhythmic drugs, how recurrences were counted. Were asymptomatic or symptomatic counted? How hard are we going to look? We know lots of people have recurrences while healing up. Are we going to count them or not? We didn’t hear back from the patient, so we assume he’s doing well and call that a cure. There are some issues related to that kind of stuff. The whole anti-coagulation issue: We don’t know what to do if these patients are chronic anti-coagulation patients, patients with hypertension diabetes, heart failure, old patients.”
The upcoming CABANA trial will go a long way in answering more clinical questions regarding treating AFib with catheter ablation, according to Drs. Naccarelli and Wilber. CABANA is designed to test whether left atrial catheter ablation treatment to eliminate AFib is superior to the current state-of-the-art therapy with either rate control or AAD for reducing total mortality (primary endpoints) and decreasing the composite endpoints of total mortality, disabling stroke, serious bleeding and cardiac arrest (secondary endpoints) in patients with untreated or incompletely treated AFib warranting therapy. Biosense Webster, St. Jude Medical, CryoCath, Bard and Boston Scientific all have catheter ablation systems that will be used in the trial.
Zayd Eldadah, M.D., Ph.D., director of cardiac arrhythmia research at The Washington Hospital Center in Washington D.C., believes cryoablation therapy is an appealing alternative energy source because of its reversibility. Ultrasound is another experimental energy source that may someday have clinical merit, said Dr. Eldadah.
Other Devices in Trials
In January Medtronic Inc. said it would acquire Ablation Frontiers, a move designed to expand Medtronic’s radiofrequency (RF) ablation technology offerings for the treatment of AFib. In 2006, Ablation Frontiers received CE Mark to begin marketing its system of catheters and the RF generator. Ablation Frontiers is conducting a clinical trial under an FDA investigational device exemption (IDE) to gain approval for permanent, or chronic, AFib in the U.S., Medtronic said.
That acquisition came on the heels of Medtronic’s acquisition of CryoCath Technologies, which makes a cryoablation treatment for AFib.
Medtronic also said in January it is expanding its CURE-AF (Concomitant Utilization of Radiofrequency Energy for Atrial Fibrillation) U.S. clinical program with a post-market study in Europe and Canada. CURE-AF is being conducted to secure FDA Clearance of Cardioblate for the investigational treatment of AFib. The program will now collect post-market data internationally on the efficacy of irrigated cardiac ablation with radiofrequency (RF) energy in AFib patients. The system has been used in more than 90,000 procedures worldwide, Medtronic said.