NIH Suspends Celebrex Trial, Orders Review of COX-2 Studies

BETHESDA, Maryland-After suspending use by study participants of the selective COX-2 inhibitor celecoxib(Drug information on celecoxib) (Celebrex, Pfizer) in the Adenoma Prevention With Celecoxib (APC) trial because of cardiovascular toxicity, National Institutes of Health (NIH) director Elias A. Zerhouni, MD, ordered a review of all NIH-supported studies involving COX-2 inhibitors. The National Cancer Institute (NCI) alone has more than 40 ongoing COX-2 prevention and clinical trials in progress, including the APC. "We are now informing all principal investigators for these studies and will ask them to communicate directly with their study participants and explain the risks and benefits," Dr. Zerhouni said. "Also, we are asking each investigator to inform us of their plans to analyze their data in light of the new information. And we are asking institutional review boards for all related trials to assess the new information, and to conduct a safety review as well." Increased Cadiovascular Events NIH suspended the administration of celecoxib to APC participants on NCI's recommendation after the study's independent safety and monitoring board found an increased risk of cardiovascular events in the trial of more than 2,000 people, which is aimed at assessing the drug's ability to prevent adenomas. All study participants had had adenomatous polyps removed and were randomized to three arms: either 200 mg or 400 mg of celecoxib twice daily, or placebo. NIH and Food and Drug Administration (FDA) officials announced suspending celecoxib's use in APC during a telephone press conference. “Patients in the clinical trial taking 400 mg of celecoxib twice daily had a 3.4 times greater risk of cardiovascu lar events, compared to those taking placebo," said FDA acting commissioner Lester Crawford, DVM, PhD. "For patients in the trial taking 200 mg of celecoxib twice daily, the risk was 2.5 times greater. The average duration of treatment in the trial was 33 months. A similar ongoing trial comparing celecoxib 400 mg once a day vs placebo in patients followed for a similar period of time has not shown an increased risk." Participants in the APC trial will no longer receive celecoxib, but they will remain under observation for the planned length of the study. The trial, which began in 2000, is scheduled to end in the spring of 2005 Vioxx Withdrawal The cardiovascular problems associated with celecoxib came to light after NCI director Andrew C. von Eschenbach, MD, ordered the addition of greater cardiovascular expertise to the safety and monitoring boards overseeing institute-sponsored studies of all drugs in the class. The order was prompted by the withdrawal of the COX-2 inhibitor rofecoxib(Drug information on rofecoxib) (Vioxx, Merck) from the market in September 2004. Merck voluntarily recalled rofecoxib after researchers found that people who took it for more than 18 months in a study testing the drug's power to prevent colon adenomas had double the risk of cardiovascular toxicities as the placebo arm. The NCI review began with the APC trial. Dr. Crawford also noted that clinical investigators have found that patients treaded with valdecoxib(Drug information on valdecoxib) (Bextra, Pfizer) have an increased cardiovascular risk after heart surgery. "Physicians should consider this evolving information in considering the risks and benefits of Celebrex in individual patients," Dr. Crawford said. "FDA advises evaluating alternative therapy. At this time, if physicians determine that continued use is appropriate for individual patients, FDA advises the lowest dose of Celebrex."