Costar II Pivotal Drug-Eluting Stent Trial Failed
Principal investigators for the COSTAR II (CObalt Chromium STent with Antiproliferative for Restenosis) trial confirmed that the study failed to meet its primary endpoint.
The COSTAR II trial compared the CoStar stent with the Taxus Express paclitaxel drug-eluting stent, and was designed to demonstrate non-inferiority at eight-month follow-up with respect to major adverse cardiac events (MACE) in patients with multi-vessel or single-vessel disease. In this trial, MACE was defined as a composite of clinically driven target vessel revascularization (re-treatment), new myocardial infarction (heart attack or MI) related to the target vessel and cardiac death related to an intervened vessel.
At eight-month follow-up, the CoStar stent had significantly higher MACE rate than the Taxus stent (11.0 percent vs. 6.9 percent; p=0.005). This difference was largely due to a significantly higher incidence of clinically driven target vessel revascularization (8.1 percent vs. 4.3 percent; p=0.002). No significant differences were found in terms of cardiac death (0.5 percent for the CoStar stent vs. 0.7 percent for the Taxus stent; p=0.541) or new MI (3.4 percent vs. 2.4 percent; p=0.242).
The investigators also reported that the protocol-defined stent thrombosis rates at nine-month were similar between both arms of the study. The total stent thrombosis rate for the CoStar stent was 0.6 percent vs. 0.1 percent for the Taxus stent (p=0.252).
"Comparably higher re-intervention rates are largely responsible for the outcome of this trial," said Mitchell W. Krucoff, M.D., from Duke Clinical Research Institute in Durham, North Carolina, who presented the primary results of the study at the conference as a global co-principal investigator. "The safety data from this trial are consistent with other drug-eluting stent studies."
As a result of these outcomes, Conor Medsystems LLC recently terminated ongoing clinical trials with the CoStar stent and halted the submission of its Pre-Market Approval application to the U.S. Food and Drug Administration for the product. Further, Conor Medsystems discontinued sale of the product through commercial partners in countries in Europe, Asia and Latin America where the CoStar stent was already approved.
The company cited potentially sub-optimal therapeutic dosing of paclitaxel as the potential reason why the COSTAR II Trial failed to meet its primary endpoint. Going forward, the company's clinical program will be heavily focused on the study of sirolimus on its platform, as well as on investigating the vast library of therapeutic agents accessible to its scientists through the research and development programs of pharmaceutical companies in the Johnson & Johnson family of companies.
"We remain optimistic about the ability of the novel Conor Medsystems reservoir platform to provide precise and controlled delivery of a therapeutic agent based on earlier proof of concept testing and trials," said Campbell Rogers, M.D., chief technology officer, Johnson & Johnson cardiovascular franchise. "We expect that the continued development of sirolimus on this platform will demonstrate promising outcomes because sirolimus has been shown to be a versatile and potent anti-restenosis agent with a wide therapeutic dosing range."