With concern growing that a popular new class of arthritis medicine might increase a patient's risk of heart attack and stroke, the maker of Celebrex -- one of the most widely sold drugs in the world -- announced yesterday that it will soon begin a major clinical trial to determine whether the drug is safe for long-term use.

Pfizer Inc. said it will begin the worldwide trial early next year. It said the study will involve 4,000 patients and run for at least two years.

Joseph Feczko, president of worldwide development at Pfizer, said that because of numerous completed studies, the company remains confident that Celebrex is safe for long-term use. The popular drug came under suspicion after Vioxx, its competitor, was withdrawn last month by Merck & Co. because of increased cardiovascular disease among users.

Nonetheless, Pfizer said the company will begin what it called the "first large-scale clinical study" looking at the risks of inflammation and cardiovascular disease in arthritic patients using the class of painkiller known as a COX-2 inhibitor. Pfizer said it will include patients at high risk of heart attack and stroke in the study.

The recent Vioxx withdrawal led the Food and Drug Administration to say more study was needed of the long-term safety of all COX-2 inhibitors. The aggressively marketed and widely used class of drugs was approved for use in the late 1990s, but none of the large clinical tests looked at the potential long-term health risks.

In the clinical trial that led to the Vioxx withdrawal, researchers found that after 18 months, people taking the drug were twice as likely to experience cardiovascular events as those taking a placebo.

On Friday, Pfizer issued a warning that its other COX-2 inhibitor, Bextra, posed a potential risk to patients given the drug during coronary artery bypass surgery but said there was no known increased risk for long-term arthritic users.

While Pfizer said it was starting the Celebrex trial to address potential cardiovascular risks, the company also said some unique characteristics of the drug may actually improve cardiovascular conditions in people with established coronary artery disease. Nonetheless, the study will be designed to answer the question of whether Celebrex increases the risk of cardiovascular events, as Vioxx was shown to do.

"This kind of trial makes a lot of sense," said Steven K. Galson, acting director of the FDA's Center for Drug Evaluation and Research.

"Given the question about whether we are seeing a class effect or something unique to Vioxx, there won't be a definitive answer until there has been an additional long-term study," he said. "I believe Pfizer understands that."

The Celebrex trial will be randomized and placebo-controlled, and will include aggressive monitoring of patients for cardiovascular problems. In the study that ultimately led to the withdrawal of Vioxx from the market, researchers found an increase in blood pressure among otherwise healthy patients almost immediately, although they did not see the more harmful cardiovascular disease rate climb until after 18 months.

People with arthritis and other consumers have embraced the COX-2 inhibitors because they relieve pain but do not cause the kind of stomach and intestinal damage often associated with long-term use of other painkillers.