The National Institutes of Health (NIH) announced today that it has suspended a large clinical trial testing whether the COX-2 inhibitor Celebrex can prevent colon polyps. Those taking the drug had an increased risk of heart attacks compared to volunteers taking placebo, results that echo similar findings with another COX-2 inhibitor--Vioxx—that forced it to be yanked from the market on 30 September.
Elias Zerhouni, the director of NIH, which was funding the suspended trial as well as dozens of others aiming to prevent cancer or Alzheimer's disease with Celebrex, said in a press conference that he has ordered a review of all NIH-funded studies of COX-2 inhibitors.
Celebrex, made by pharmaceutical giant Pfizer, has been under a microscope since the drug company Merck announced that it was pulling Vioxx off the market. A study testing Vioxx's ability to stem polyps in 2600 volunteers found that after 18 months, participants on Vioxx were twice as likely to suffer a heart attack or stroke as those on placebo. The withdrawal of Vioxx raised questions about whether the problems with Vioxx might plague other COX-2 inhibitors as well. Earlier this month, the Food and Drug Administration added a warning to the COX-2 inhibitor Bextra, contraindicating its use in patients undergoing bypass surgery.
Pfizer has defended Celebrex as safe but is now evaluating the new data. The National Cancer Institute-funded study, involving 2000 people, was testing whether Celebrex could prevent colon polyps, a precursor of colon cancer, in at-risk patients. Following additional scrutiny after Vioxx's withdrawal, and the addition of cardiovascular experts to the trial's data safety monitoring board, the DSMB concluded that patients taking a high dose of Celebrex had a 3.4-fold increase in the risk of heart attacks or strokes compared to those on placebo; those on a moderate dose had a 2.5-fold increase in risk.
Since the announcement this morning of the trial's suspension, at least two other related trials have been temporarily halted: a colon polyp prevention study that began recruiting this year and was aiming for 1200 participants, and a breast cancer treatment trial that also began this year, aiming to recruit 2700 women, says Charles Geyer, director of medical affairs for the National Surgical Adjuvant Breast and Bowel Project (NSABP), a group that runs cancer trials and is itself funded by NIH. So far, NIH is apparently not suspending other Celebrex trials, including two that have over 1000 participants--at least not immediately, in part, says Zerhouni, because a another Celebrex trial that closely resembles the suspended trial hasn't found the same problems. But investigators are holding their breath. "There are major questions to be answered about whether we continue," says Peter Lance of the University of Arizona in Tucson, who's running a large colon polyp prevention trials, slated to enroll 1600 people.