A meeting of the Circulatory System Devices Panel was held on April 23, 2009, to discuss and vote on the premarket approval application PMA P080022) for the Atritech, Inc. WATCHMAN® Left Atrial Appendage (LAA) Closure Technology. The Panel listened to the Company and FDA presentations, discussed the clinical data presented, addressed the FDA questions, and finally voted (7-5-0) to recommend that the PMA application for the WATCHMAN® LAA Closure Technology be found “Approvable with Conditions.”
The WATCHMAN® device is a percutaneously delivered permanent implant placed in the left atrial appendage in order to occlude the appendage and prevent systemic embolization of thrombus, specifically stroke.
The PROTECT AF trial was conducted to evaluate the WATCHMAN ® Left Atrial Appendage (LAA) Closure Technology versus warfarin, in patients with non-valvular atrial fibrillation at risk of stroke. The trial enrolled 800 patients and was conducted in 60 centers across the United States and Europe.
The following indication for use has been proposed for the WATCHMAN device:
“The WATCHMAN® Left Atrial Appendage (LAA) Closure Technology is intended as an alternative to warfarin therapy for patients with non-valvular atrial fibrillation. The WATCHMAN LAA Closure Technology is designed to prevent embolization of thrombi that may form in the LAA, thereby preventing the occurrence of ischemic stroke and systemic thromboembolism.”
Trial Name: PROTECT AF = WATCHMAN LAA Closure Technology for Embolic PROTECTion in Patients with Atrial Fibrillation. The objective of the Protect AF study was to demonstrate the safety and efficacy of the WATCHMAN device for the prevention of ischemic stroke and systemic thromboembolism in patients with non-valvular atrial fibrillation who require treatment for potential thrombus formation and who are eligible for warfarin therapy.
The design was a prospective, multicenter, randomized controlled trial comparing device implantation plus short term (45-days) warfarin therapy (WATCHMAN) to warfarin therapy (Control).
During the deliberations the panel largely felt short term efficacy had been demonstrated by the data available from the PROTECT AF trial. However, due to the lack of available long-term data, longer term efficacy had not been adequately demonstrated with this implant. There were varied opinions on whether adequate safety information exists on use of this device. Discussion ranged from the potential for improved safety compared to long-term warfarin use to concerns about the peri-procedural risks associated with device placement.
The panel discussed the indications for use proposed by the applicant and felt that the wording should be modified to the following or similar wording: intended as a non-inferior treatment to long-term warfarin therapy in patients with non-valvular atrial fibrillation to reduce the risk of ischemic stroke, cardiovascular or unexplained death, and systemic embolization.
The panel discussed in detail a possible physician training plan that would be necessary for physicians should the device be approved. The panel concurred on a certification program for implanting physicians, including a minimum of three guided successful implantations, proficiency in trans-septal catheterization and an on-line training program for trans-esophageal echocardiography (TEE) operators.
The panel deliberated on possible changes to the labeling including adding Contraindications and Warnings/Precautions. The recommendations included (1) that FDA include appropriate wording about use of the device in patients who are unable to take warfarin, (2) that the labeling describe that there are alternatives to device or warfarin treatment in patients with a CHADS2 score of 1 (e.g., per AHA guidelines,) and (3) that the labeling include recommendations for TEE studies on follow-up for patients who receive the device.
Following presentations by the sponsor and the FDA, and after extensive deliberation, the Panel voted (7 in favor, 5 opposed; 0 abstained) in favor of “Approvable with Conditions.” The recommended conditions of approval are summarized as follows:
- Indications to be changed as discussed. 11:1 in favor
- Postapproval registry of approximately 2000 newly enrolled patients, followed to at least 2 years to evaluate acute procedural and longer term outcomes, similar to those from the pivotal study, with FDA to make the final recommendations with respect to study size. In addition, that the patients enrolled in the premarket trial (PROTECT AF), both arms, be followed for 5 years. 12:0 in favor
- Physician certification program as discussed. 12:0 in favor
- Labeling to specify that device implantation should only be performed at institutions where cardiac surgeon and facilities for cardiac surgery are accessible (urgently available). 9:3 in favor
Contact: James Swink, Executive Secretary,
(240) 276-4050 James.Swink@fda.hhs.gov
Transcripts may be purchased from: (written requests only)
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