Pfizer's support for a massive study of Celebrex safety brings the drug maker together with researchers who have been urging the company to conduct additional trials; Pfizer approached Cleveland Clinic cardiovascular researchers about conducting the trial, which was announced Dec. 13.

Steven Nissen, medical director of the clinic's Cardiovascular Coordinating Center, has been named lead investigator.

Though Pfizer is funding the study, "Dr. Nissen emphasizes that the leadership and conduct of the trial will be directed independently by the Cardiovascular Coordinating Center," the Cleveland Clinic said Dec. 13. The trial's executive committee includes a staff member from the National Heart, Lung & Blood Institute.

The funding gives Nissen the chance to conduct a study that he has advocated for many years.

In 2001, Nissen and colleague Eric Topol, who was recently demoted in a dispute with the Clinic's leadership, proposed a CV safety trial in a Journal of the American Medical Association article (¹ Also see "Merck Vioxx Warning Letter Could Be Incentive For Large Cardio Safety Study" - Pink Sheet, 1 October, 2001., p. 22).

A large, long-term study on NSAIDs also was proposed by FDA Office of Medical Policy Director Robert Temple, during a February advisory committee meeting on the safety of COX-2 inhibitors (² Also see "“ALLHAT”-Type Cardio Safety Trial For COX-2s, NSAIDs Urged By FDA" - Pink Sheet, 28 February, 2005., p. 11).

The scale and prominence of the research alone could be read as a signal from Pfizer about its faith in the product.

If successful, the 20,000-patient, $100-million study could provide the convincing evidence of Celebrex's safety that the drug maker has been pursuing ever since the September 2004 withdrawal of Merck's Vioxx from the market due to concerns about cardiovascular risk.

A study affirming the safety of Celebrex when compared to ibuprofen or naproxen would aid Pfizer in rebuilding the brand following concerns about CV risk associated with COX-2 inhibitors, which has resulted in a "black box" warning and declining sales (³ Also see "Pfizer Celebrex Revised Labeling Adds Class Cardio Risk, Moves Safety Data" - Pink Sheet, 8 August, 2005., p. 6).

Shortly after the Vioxx recall, Pfizer announced plans for a 4,000-patient, two-year study to show Celebrex is cardioprotective.

The company also ran an advertisement that questioned the safety of OTC pain relievers. The ad directed consumers to a website which offered a seven-day free trial of Celebrex and said that "serious" and "even deadly" side effects could result from use of some OTCs (⁴ Also see "Pfizer Goes On Offense With Celebrex: TV Ads, Study Proposal Stress Safety" - Pink Sheet, 25 October, 2004., p. 12).

The cardiovascular risks seen in Vioxx may result from Vioxx-specific metabolites rather than COX-2 inhibition itself, Pfizer suggested in briefing papers submitted prior to a Feb. 16-18, 2005, FDA advisory committee meeting.

The worldwide clinical trial will compare the cardiovascular safety of ibuprofen, naproxen and Celebrex (celecoxib). The undertaking marks the first large-scale NSAID trial to exclusively study patients at high risk of heart disease, the Cleveland Clinic said.

Osteoarthritis patients with coronary heart disease or multiple risk factors for heart disease are the focus of the "Prospective Randomized Evaluation of Celecoxib Integrated Safety vs. Ibuprofen or Naproxen" (PRECISION) study. Some patients with rheumatoid arthritis also will be included.

Trial participants will be randomly assigned to one of the three drugs and followed for an average of two years. The two-year study will track serious cardiovascular events such as death, heart attack and stroke. All patients will take Prilosec for gastrointestinal side effects, while some will receive low-dose aspirin if indicated by current guidelines.

The study will evaluate only prescription doses of naproxen (500 mg twice daily) and ibuprofen (800 mg twice daily), and is expected to provide new information on NSAID use by those patients at highest risk of cardiovascular events.

"Prior trials of pain relievers have not focused on these high-risk patients," Nissen said in a release. "Currently available information is insufficient to determine whether typical dosages of celecoxib and other popular pain relievers are linked to an increased risk of heart disease."

Enrollment begins in 2006 and is expected to last 18 months. Study results are expected in four years, Nissen said.

Celebrex Heart Risk To Be Assessed By Cleveland Clinic In Pfizer-Funded Study

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