A meeting of the Circulatory System Devices Panel was held on October 22 and 23, 2002. On October 22, the Panel discussed, made recommendations, and voted on a premarket approval application, Cordis’ Corporation CYPHER™ Sirolimus-Eluting Coronary Stent System (P020026). The device is a combination product, consisting of a permanently-implanted stent with a conformal drug/polymer coating and the CYPHER™ Delivery Catheter System. The stent is intended to reduce restenosis of de novo coronary artery lesions in patients with coronary artery disease. The company completed a clinical study with 1,058 patients randomized into two treatment arms: 533 patients received the Sirolimus-Eluting stent and 525 received a bare metal coronary stent. The CYPHER™ Sirolimus-Eluting Coronary Stent System reduced target vessel failure at nine months to 8.6% compared to a 21% rate for patients treated with the bare metal stent.
Following presentations by the sponsor and the FDA, and after questioning the sponsor and deliberating, the Panel voted (8-0) that the application be found ‘approvable with conditions’. The Panel’s conditions included recommendations for five year follow-up of patients enrolled in the three principal clinical studies conducted to date, completion of a pharmacokinetic study and revisions to the patient and product labeling to include more information regarding the drug coating and reflect the vessel diameter (2.5 to 3.5 mm) and lesion length (15 to 30 mm) studied in the clinical trial.
A Panel meeting was held to discuss the EMBOL-X Aortic Filter 510(k) (K022071) in light of some issues raised during the 1289 patient clinical study, potentially affecting the safety and/or risk profile of the device.
The EMBOL-X Aortic Filter is “intended to contain and remove particulate emboli from the ascending aorta during and following cross-clamp removal and as the heart resumes ejection”. The heparin-coated filter has a pore size of 120 microns and is mounted on a nitinol frame. The filter is inserted into the ascending aorta via a side-port on the EMBOL-X Cannula. The flexible wire filter frame expands upon insertion into the vessel, and is available in 5 sizes. The filter is then retracted back through the same side-port at the end of the procedure.
The major issues discussed were:
- Does the device demonstrate a reasonable safety profile in light of the equivalence safety endpoint and the endothelial injuries demonstrated with the device?
- Can this method of embolic entrapment be extrapolated to clinical efficacy?
- Labeling, specifically the appropriate patient population that should be identified in the indications for use and labeling.
The Panel concluded that the device demonstrated equivalent safety as compared to the control. The issue of the endothelial injuries was neutralized by the fact that short-term imaging data indicate that the injuries are not associated with short-term clinical events (7.0 days).
The Panel had several discussions, as has the FDA, on the issue of clinical efficacy and the fact that the study was unable to demonstrate any clinical benefit, although some capture of debris was noted in 96% of the filters deployed. Although intuitively one would assume that clinical benefit would be demonstrated with the capture of debris, it wasn’t demonstrated in this study. As such, the labeling should steer clear of these implications.
It was basically discussed that the labeling should include clearly and decisively the patient population studied, and that no safety data is available for patients outside the definition of those studied. Specific patient demographics from the study should be presented in the labeling, along with more precise explanations of the inclusion/exclusion criteria defined in the study.
For the patient population studied, the RISK/BENEFIT profile is neutral (i.e., no real risk, and no clinical benefit).
For a higher risk patient population, the RISK/BENEFIT profile is not clear (e.g., risk may be greater, but there may be clinical benefit).
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