Cath Lab Digest - February 2008 - (Page 9)

9 Table 1. The ENDEAVOR Trial Series Abbreviations ABR: Angiographic binary restenosis IVUS: Intravascular ultrasound MACE: Major adverse cardiac events MI: Myocardial infarction TLR: Target lesion revascularization TVF: Target vessel failure, a composite endpoint, which includes death, myocardial infarction and target vessel revascularization. TVR: Target vessel revascularization The following trials are part of the premarket safety and efficacy package presented to the U.S. FDA on October 10, 2007. ENDEAVOR I (First-in-Man) A 100-patient first-in-man study, conducted in Australia and New Zealand. The ENDEAVOR I study showed a 24-month TLR rate of 2.0%, the same rate reported at 12 months. ENDEAVOR II (Endeavor versus the Driver bare metal stent) A randomized, double-blind pivotal trial designed to evaluate the safety and efficacy of the Endeavor stent compared to Medtronic’s Driver cobalt alloy bare metal stent. The trial enrolled 1,197 patients at 72 facilities in 17 countries. The primary endpoint of the trial was TVF at nine months. The study met all of its endpoints, including a 48% reduction in TVF, and a 61% reduction in TLR between the Endeavor arm and the control group. Angiographic results of the study demonstrated a significant reduction in restenosis rates at eight months. The study showed a 72% reduction in in-stent ABR in the Endeavor arm versus the Driver arm, and the in-segment ABR rate was reduced by 62%. Additionally, the rate of stent thrombosis was just 0.5% for the 598 patients in the trial who received the Endeavor stent, not statistically different from the 1.2% rate among those who received a bare-metal stent. Between 30 days and 9 months, there were no observations of late stent thrombosis. ENDEAVOR II CA (Continued access safety) Enrolled 296 patients. ENDEAVOR III (Endeavor versus Cypher) ENDEAVOR III was a randomized trial evaluating the safety and efficacy of the Endeavor stent with the drug compound ABT-578 (zotarolimus) compared to the Cypher ™ sirolimus-eluting stent (Cordis Corporation, a Johnson & Johnson company). The study included 436 patients randomized 3to-1 against Cypher (323 receiving Endeavor), with a primary endpoint of in-segment late lumen loss at eight months. Secondary endpoints included TLR, TVR, TVF and MACE at nine months, and ABR at eight months. The ENDEAVOR III protocol mandated angiographic follow up for all patients. 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 <0.20mm required to achieve the non-inferiority endpoint. 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 MI rate at 30 days of 0.6%, while Cypher was 7.1% with a 3.5% MI 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. ENDEAVOR IV (Endeavor versus Taxus) Randomized clinical trial evaluating 1,548 patients at 80 clinical centers in the United States, with a primary endpoint of TVF at nine months and a secondary endpoint of MACE at 30 days. The trial includes angiographic and IVUS follow up at eight months for a subset of 328 patients. The Endeavor stent met the trial’s primary endpoint, demonstrating a similar overall safety profile (equivalent rates of death, MI, and repeat procedures) to the Taxus paclitaxel-eluting stent at 1 year. In addition, the Endeavor stent showed a lower rate of non-Q-wave MI at 30 days, but a higher rate of angiographic late loss at eight months compared to the Taxus stent. TVF occurred in 6.6 percent of patients receiving the Endeavor stent and 7.2 percent of patients receiving the Taxus stent, a difference that was not statistically significant. At 12 months, the difference between the rates of TLR with the Endeavor (4.5 percent) and Taxus (3.2 percent) stents was not statistically significant. Likewise, TVR rates at 12 months were also similar (6.3 percent with Endeavor vs. 6.7 percent with Taxus). At 30 days, rates of non-Q-wave MI were 0.5 percent with Endeavor compared with 2.2 percent with Taxus, a statistically significant difference. Angiographic follow up showed late loss at eight months to be significantly greater with Endeavor (0.67 mm) compared with Taxus (0.42 mm). In the diabetic subset of 477 patients, Endeavor had similar efficacy compared with Taxus, including TLR and in-segment restenosis. ENDEAVOR PK (Pharmacokinetic) Enrolled 43 patients. ENDEAVOR-Japan A single-arm, prospective multi-center study with 99 patients and a primary endpoint of TVF at 9 months. Twelve-month data was presented in abstract form at TCT 2007. PROTECT (Patient Related OuTcomes with Endeavor versus Cypher stenting Trial) (ongoing) This study will enroll approximately 8,800 “real world” patients at 200 clinical centers worldwide. The primary endpoint for the PROTECT study will be overall stent thrombosis at three years, defined as definite and probable, according to the new Academic Research Consortium criteria. Secondary endpoints include a composite of death and non-fatal myocardial infarction, as well as numerous additional safety and clinical efficacy endpoints. E-Five international registry (ongoing) The e-Five registry is an 8,000 patient prospective, multi-center study designed as an “all comers” trial to assess the safety of the Endeavor stent at more than 200 sites in Europe, Asia, Australia, and other locations outside the United States, with a primary endpoint of MACE at one year. The study has enrolled approximately 2,500 patients. The interim results of E-Five on nearly 2,000 patients were reported at TCT 2007. A low rate of MACE (7.0%) was observed, as was a low rate of TLR of 3.8%. Thirty-four percent of the patients had diabetes and 62% had complex lesions. Cardiac death was observed at 2.0%, myocardial infarction at 1.3% and stent thrombosis of only 1.1%. The complete 12-month results on all 8,260 patients will be presented at EuroPCR in May 2008. The following trial was not part of the presentation to the FDA. RESOLUTE (next-generation polymer) The RESOLUTE study enrolled 130 patients at 12 clinical sites in Australia and New Zealand. Medtronic’s next-generation drug-eluting stent uses the same stent platform and drug as the Endeavor stent (the Driver bare-metal cobalt alloy stent and zotarolimus, or ABT-578), but incorporates a proprietary, biocompatible drug delivery polymer developed by Medtronic instead of PC Polymer licensed from Abbott. In clinical results at nine months, presented at the EuroPCR meeting in May 2007, the Endeavor RESOLUTE trial showed no TLR, no TVR and a MACE rate of 7.0%. Of the trial’s 130 patients, 129 (99.2%) received clinical follow-up, and 95 had angiographic follow-up. In-stent late lumen loss, the study’s primary endpoint, was 0.22 mm, while in-segment late loss was 0.12 mm. In-stent ABR was 1.0% percent and in-segment ABR was 2.1%. The average lesion length in the RESOLUTE trial was 15.5 mm and nearly 82% of enrolled patients were classified as having challenging B2/C lesions. ■

Table of Contents Feed for the Digital Edition of Cath Lab Digest - February 2008

Cath Lab Digest - February 2008 Bay Regional Medical Center ENDEAVOR IV: A Zotarolimus-Eluting Stent Versus a Paclitaxel-Eluting Stent in a Randomized Clinical Trial A 3D CT Vessel “Roadmap” Over Live Fluoroscopy for Chronic Total Occlusions Contents Clinical Editor’s Corner An Evaluation of Cath Lab Turnaround Time Commentary: An Evaluation of Cath Lab Turnaround Time Excerpts from Chapter 19. STEMI Interventions – Future Perspectives The Potential Clinical Utility of Intravascular Ultrasound Guidance in Patients Undergoing Percutaneous Coronary Intervention With Drug-Eluting Stents The Ten-Minute Interview with…Debbie Charlton, RN The Society of Invasive Cardiovascular Professionals (SICP) at Transcatheter Cardiovascular Therapeutics (TCT) 2007 The Cath Lab is a Business: Do You Have the Knowledge to Stay Afloat? Incidence and Predictors of Vascular Complications after Invasive Coronary Procedures: A Prospective Analysis Ask the Clinical Instructor: A Q&A Column for those New to the Cath Lab Volunteer Survey SICP* Section Meetings Calendar What Do You Think? CEU Education Center Clinical & Industry News Classifieds Advertisers Index

Cath Lab Digest - February 2008

For optimal viewing of this digital publication, please enable JavaScript and then refresh the page. If you would like to try to load the digital publication without using Flash Player detection, please click here.