Trial of naproxen and celecoxib suspended

Use of study drugs in a large, federally funded Alzheimer prevention trial has been suspended following a decision by the study's leadership on Dec. 17, 2004.

The Alzheimer's Disease Anti-Inflammatory Prevention Trial (ADAPT), sponsored by the National Institutes of Health (NIH), was designed to test whether either of two nonsteroidal anti-inflammatory drugs (NSAIDs) could prevent Alzheimer's in older adults at increased risk due to a family history of the disease. Naproxen (sold under such trade names as Aleve, Naprosyn and Anaprox) and celecoxib (Celebrex) were the two NSAIDs under investigation in the trial.

Although administration of study drugs is suspended, researchers will continue to examine and monitor ADAPT's approximately 2,400 participants, who have been taking naproxen, celecoxib or a placebo for up to three years.

The suspension came following concerns over data from a cancer prevention trial unrelated to ADAPT suggesting that celecoxib may be associated with an increased risk of heart problems. Use of study drugs in the cancer trial was also suspended on Dec. 17. Although preliminary data from ADAPT did not link celecoxib to a statistically significant increase in heart problems, preliminary ADAPT data did suggest a possible link between long-term use of naproxen and increased risk of heart attack and stroke. Naproxen, approved by the Food and Drug Administration (FDA) in 1976 and sold over the counter since 1994, has never previously been linked to cardiovascular problems, although the drug has not been tested for long-term use in placebo-controlled clinical trials.

Last September, rofecoxib (Vioxx), a drug in the same NSAID subclass as celecoxib, was withdrawn from the market after data from another prevention trial highlighted potential cardiovascular problems. Valdecoxib (Bextra), another drug in this subclass, has also been linked to cardiovascular problems following heart bypass surgery and is not recommended for use by individuals at high risk for heart disease.

FDA officials called the situation with regard to NSAID safety "confusing." The agency is in the process of reviewing all available data about the drugs and will hold a meeting in February to discuss future regulatory implications. The agency has issued interim guidance on NSAID use for health professionals and consumers in the form of a Dec. 24 talk paper and a Dec. 23 public health advisory.

The FDA, NIH and National Institute on Aging (NIA) have all said that more information for consumers and health professionals will be issued as soon as scientifically sound conclusions can be drawn from the data.

Prevention trials, because they tend to be very large and last for several years, may increase the possibility that researchers will notice side effects associated with long-term use of drugs. Another potential complicating issue is that a stricter safety standard may be necessary for a drug when it is used to prevent healthy people from developing a disease than when it is used to treat a disabling or life-threatening disorder.