ENDEAVOR III Confirmatory Study Demonstrates Clinical Outcomes Consistent With Previous Endeavor Trials
No Statistical Differences in Clinical Outcomes Between Endeavor and Cypher
Despite
Narrowly Missing Angiographic Primary Endpoint
WASHINGTON, Oct. 17, 2005 -- David E. Kandzari, M.D., Co-Principal Investigator
of the ENDEAVOR III clinical trial and Assistant Professor of Interventional
Cardiology at Duke Medical Center, today presented results of the ENDEAVOR III
clinical trial at the Cardiovascular Research Foundation's (CRF) Seventeenth
Annual Transcatheter Cardiovascular Therapeutics scientific symposium in Washington,
D.C. The ENDEAVOR III trial, a confirmatory study, demonstrated that the Endeavor™ drug-eluting coronary stent provides clinical and angiographic outcomes that are consistent with previous Endeavor trials.
"The two objectives of this trial were to compare in-segment late loss between the Endeavor stent and the Cypher stent, and also to see if the superior angiographic and clinical results achieved with the Endeavor stent in the international ENDEAVOR II trial could be replicated in a United States patient population," said Dr. Kandzari. "The non-inferiority endpoint was not reached, but as a confirmatory study, this trial definitively showed that the safety and efficacy results were achievable in a U.S. population. One of the key takeaways from this trial should be that the ENDEAVOR III clinical and angiographic outcomes are equivalent to those seen in ENDEAVOR II. In addition, there were no statistically significant differences in the clinical outcomes between Endeavor and Cypher. However, the study did show a significant procedure success rate in favor of Endeavor when it came to deliverability and a lower rate of in-hospital myocardial infarctions."
Sponsored by Medtronic, Inc. (NYSE:MDT - News), ENDEAVOR III was a randomized
trial evaluating the safety and efficacy of the Endeavor stent with the drug
compound ABT-578 compared to the Cypher™ Sirolimus-eluting stent marketed by
Cordis Corporation, a Johnson & Johnson company. The study included 436 patients
randomized 3-to-1 against Cypher (323 receiving Endeavor), with a primary endpoint
of in-segment late lumen loss at eight months. Secondary endpoints included Target
Lesion Revascularization (TLR), Target Vessel Revascularization (TVR), Target
Vessel Failure (TVF) and Major Adverse Cardiac Events (MACE) at nine months,
and Angiographic Binary Restenosis (ABR) at eight months. The ENDEAVOR III protocol
mandated angiographic follow-up for all patients.
Scott Ward, president of Medtronic Vascular, noted that the Endeavor clinical program is continuing to gain momentum as various key milestones have now been achieved. Following CE mark approval in late July, Medtronic has successfully launched the Endeavor stent in international markets, with positive physician feedback. The company filed its first PMA module with the U.S. Food and Drug Administration earlier this month, and enrollment in ENDEAVOR IV, another large confirmatory trial, is progressing as planned. The company remains on track for PMA approval in calendar year 2007.
"The clinical performance of the Endeavor drug-eluting stent has been remarkably consistent in all three of our major clinical trials completed to date," said Ward. "The combined analysis across the entire spectrum of Endeavor trials reveals that 95.1% of the 1,300 patients receiving the Endeavor stent did not need target lesion revascularization in the nine months following the procedure. We also continue to be very encouraged by our safety profile, as we have observed no late stent thrombosis with Endeavor in any of our trials. In fact, among these 1,300 patients, we have observed no stent thrombosis beyond 10 days of the procedure."
In the ENDEAVOR III trial, the Endeavor arm showed an in-segment late loss of 0.34mm, consistent with the rate observed in ENDEAVOR II, while the Cypher stent had late loss of 0.13mm. The 0.21mm difference narrowly missed the margin of less than or equal to 0.20mm required to achieve the non-inferiority endpoint. It is important to note, however, that late loss is an angiographic surrogate marker and clinical endpoints such as TLR and MACE are typically considered more important by clinicians.
"We don't routinely bring patients back to the cath lab because of concerns over late loss," Kandzari said. "Instead, we bring them back due to recurrent symptoms related to the development of restenosis. What is very interesting is that the observed difference in late loss did not translate into differences in any of the clinical results."
In the trial, the TLR rate for Endeavor was 6.3%, nearly identical to the 5.8% for Endeavor patients who underwent angiography in the previous ENDEAVOR II trial. The TLR rate for Cypher in ENDEAVOR III was 3.5%, although with only 113 patients in the Cypher arm, the study was not "powered" for statistical significance of secondary endpoints. The MACE rate in the Endeavor arm was 7.6% with a non-Q wave myocardial infarction (heart attack) rate at 30 days of 0.6%, while Cypher was 7.1% with a 3.5% myocardial infarction rate. In addition, Endeavor proved to be better than Cypher in deliverability, with a procedural success rate of 98.1% compared to 91.2% for Cypher, a statistically significant finding. Early and late stent thrombosis did not occur in either group.
"The Endeavor clinical program continues to provide strong evidence that this stent is safe for patients and effective at reducing target lesion revascularization," said Martin B. Leon, M.D., Columbia University Hospital, New York, chairman of the Cardiac Research Foundation and ENDEAVOR III co-principal investigator. "The ENDEAVOR IV study, which has a clinical endpoint instead of an angiographic surrogate, should provide even more insightful information about the Endeavor stent system and we look forward to the results of that trial."
The ongoing ENDEAVOR IV trial is a randomized study at 80 centers in North America comparing the Endeavor stent with the Taxus stent from Boston Scientific in 1,548 patients. The primary clinical endpoint of the study is target vessel failure at 9 months. The study is on pace to complete enrollment in the first half of 2006.
The Endeavor stent is made of a cobalt alloy and has a unique modular architecture designed to enhance deliverability over standard bare metal stents. In addition to the proprietary drug compound ABT-578, the Endeavor stent is coated with phosphorylcholine (PC), a polymer designed to simulate the outside surface of a red blood cell and mimic the structure of the natural cell membrane.
About Medtronic
Medtronic, Inc. (www.medtronic.com), headquartered in Minneapolis, is the global leader in medical technology - alleviating pain, restoring health, and extending life for millions of people around the world.
This press release contains forward-looking statements, including statements regarding anticipated regulatory approval and study completion dates, which are subject to risks and uncertainties, such as governmental regulation, general economic conditions and others described in Medtronic's Annual Report on Form 10-K for the year ended April 29, 2005. Actual results may differ materially from anticipated results. Medtronic does not undertake to update its forward-looking statements.
Caution: The Endeavor Drug Eluting Coronary Stent is an investigational device with an investigational drug (ABT-578) and exclusively for clinical investigation.
Contact:
Medtronic, Inc.
Public Relations:
Scott Papillon, 707-591-7367
or
Rob Clark, 763-505-2635
or
Investor Relations:
Rachael Scherer, 763-505-2694
or
Jeff Warren, 763-505-2696
Source: Medtronic, Inc. |
