• To evaluate the safety of treatment with the Arctic Front™ Cardiac CryoAblation Catheter System, including the FlexCath™ Steerable Sheath and Freezor® MAX Cardiac Cryoablation Catheter, compared to a randomized drug control group, by assessing the [ Time Frame: After the last patient is enrolled and the 12-month follow-up is terminated. ] [ Designated as safety issue: Yes ]
  

• To evaluate the effectiveness of treatment with the Arctic Front™ Cardiac CryoAblation Catheter System, including the FlexCath™ Steerable Sheath and Freezor® MAX Cardiac Cryoablation Catheter, compared to a randomized drug control group, by assess [ Time Frame: After the last patient is enrolled and the 12-month follow-up is terminated. ] [ Designated as safety issue: No ]
  

Atrial fibrillation (AF) is a common and disabling cardiac arrhythmia, affecting 1 to 1.5 million Americans. In addition to hemodynamic compromise and higher mortality rates, AF patients suffer an increased risk of systemic emboli arising from the left atrium (LA). The risk of stroke in patients with nonvalvular AF is 5 to 7 times greater than in comparable patients without AF; overall, 20 - 25% of ischemic strokes are due to cardiac emboli, of which half arise in patients with nonvalvular AF. In addition to such proven mortality and morbidity risks, AF is associated with a substantial burden of symptoms, stemming from the arrhythmia itself, exacerbation of comorbid conditions such as CHF, associated anxiety over possible sequelae as well as the substantial burden of side effects from antiarrhythmic drugs used to treat AF ("AF drugs" or AFDs). Currently available treatments are unsatisfactory for many patients. AFD treatment has a relatively low efficacy even in patients suffering from paroxysmal atrial fibrillation (PAF), with frequent recurrences and a high incidence of intolerable drug side effects. Ablation of pulmonary veins (PVs) using radiofrequency (RF) catheters has shown some level of clinical success in the treatment of PAF, but has been associated with serious complications, including PV stenosis, thromboembolic phenomena, cardiac perforation, phrenic nerve palsies, esophageal fistulae and pericardial tamponade. Furthermore, RF energy effects are rapidly irreversible and cannot be used to temporarily alter and reversibly assess the electrophysiologic functions of the cardiac conduction tissue adjacent to the ablating catheter. Ultrasound energy has been used with a balloon system to deliver heat to create a circumferential lesion at the os of the PVs. This system is under investigational testing in the U.S. and early results have shown moderate clinical success with multiple applications of energy. Thromboembolic incidents as well as irreversible phrenic nerve damage have also been reported. CryoCath Technologies has developed and tested the Arctic Front™ Cardiac CryoAblation Catheter System (with the FlexCath™ Steerable Sheath) and the Freezor® MAX Cardiac Cryoablation Catheter—the subjects of this investigation—to allow the rapid formation of continuous cryoablation lesions at the PV ostia. While it has a balloon rather than focal or linear cooling segment, it otherwise has the same principles of operation and comprehensive safety features as the 7F Freezor® Focal Ablation Catheter, which was the subject of PMA P020045, and the 7F Arctic Circler™ Curvilinear Cryoablation Catheter (IDE G030159). (Please see Section 2.9 for a description of the device system.)Pre-clinical data have demonstrated long-term effectiveness of balloon cryoablation for permanent electrical isolation of the PVs with low risk of PV stenosis. The potential of focal and linear cryoablation in the treatment of patients with PAF has been studied in clinical studies PS-005 and PS-009. Results from these studies suggest that no pulmonary venous stenosis and no thromboembolic incidents have occurred even with multiple 4 or 8-minute cryoapplications. However, achieving an adequate therapeutic effect using focal or linear cryolesions often required multiple applications and lengthy procedure times. Balloon cryoablation of subjects with PAF has been studied in PS-011, a feasibility study of the Arctic Front™ Balloon Cardiac CryoAblation Catheter System, in conjunction with the Freezor® MAX and Xtra and the Arctic Circler Linear™ Cardiac CryoAblation Catheter. Twenty (20) subjects were enrolled at two European centers using the 23 mm Arctic Front™ Balloon, and an additional 7 subjects were enrolled using 28 mm Arctic Front™ Balloon. Acute procedural success was 100%, and long term follow-up reveals a high rate of freedom from recurrent AF. A low incidence of adverse events was noted, with two patients experiencing reversible loss of phrenic nerve capture during the procedure. Both patients recovered fully. Of the original 20 subjects treated with the 23 mm balloon, 16 / 20 (80%) were AF-free between the 6 and 12 month follow-up visits.

Of the additional 7 subjects treated with the 28 mm balloon, 5 / 6 (83%) were AFfree through 6 months. Another non-randomized feasibility study of the Arctic Front™ 23 mm Balloon Cardiac CryoAblation Catheter System under protocol PS-012 has completed enrollment at four centers in the United States. Based on incompletely monitored data, as of July 12th, 2006, 31 patients have undergone a successful cryoablation procedure with Acute Procedural Success (isolation of ≥ 3 PVs) in 100% (31 / 31 subjects). Electrical isolation was achieved in 129 / 130 PVs (99.3%). A total of 67 AEs have been reported, and no deaths. Nine (9) serious adverse event (SAEs) have been reported. Four device related SAEs involved changes in phrenic nerve conduction: 3 patients had cryoablation discontinued immediately and nerve function recovered completely by 1 month, and the fourth subject had transient loss of capture during the procedure, followed at the 1 month visit by shortness of breath, a viral infection and slight paralysis of a hemidiaphragm. Two other device related SAEs were a pericardial tamponade requiring pericardiocentesis and hospitalization, and a right groin hematoma. Three additional non-device related SAEs included one episode of chest pain, one instance of right neck bleeding after vascular access and one instance of left groin site bleeding after vascular access. Long term follow-up for PS-012 is incomplete, but 17 subjects have reached 3 months, and 14 / 17 (82%) are free from recurrent AF. Only one of these 14 subjects was on a previously failed AF drug, giving a 76% (13 / 17) rate of freedom from recurrent AF off drugs. Based on these encouraging results, this pivotal clinical study has been designed to provide valid scientific evidence of the safety and effectiveness of the Arctic Front™ Cardiac CryoAblation Catheter System (with a FlexCath™ Steerable Sheath) with the adjunctive use of the Freezor® MAX Cardiac Cryoablation Catheter to electrically isolate PVs in patients with PAF, and thereby reduce the recurrence of PAF compared to a randomized drug control group.