The Cleveland Clinic will lead a huge international study to learn whether painkillers taken by millions of Americans for arthritis are safe for those at risk of heart problems.
With an unusual mix of industry, academic researchers and government oversight, the study also aims to restore public confidence in the wake of the Vioxx debacle.
“There’s only one way — through good science,” said Dr. Steven Nissen, the Cleveland cardiologist who will lead the study. “We know the burden is upon us to do this right.”
Drug safety and the credibility of research have been concerns in recent months since Vioxx and Bextra were pulled from the market because of evidence they can raise the risk of a heart attack or stroke. That left Pfizer Inc.’s Celebrex as the only available cox-2 inhibitor, drugs that became blockbusters because they were gentler on the stomach than older pain relievers.
Many people who switched to over-the-counter pain relievers called non-steroidal anti-inflammatory drugs, or NSAIDs, then had a new worry when the Food and Drug Administration ordered stronger warning labels earlier this year.
The new study will test Celebrex and two types of NSAIDs — ibuprofen (sold as Motrin, Advil and other brands) and naproxen (Naprosyn, Aleve).
About 20,000 people throughout the United States, Eastern Europe, Canada, Australia and South America will be randomly assigned to get one of the three — neither they nor their doctors will know which — and a drug to prevent stomach irritation so each pain reliever’s true effectiveness can be assessed. Drugs and follow-up medical monitoring will be free.
To be eligible, participants must have had a heart problem in the past, such as a heart attack, blocked arteries or chronic chest pain, or diabetes, stroke or clogged vessels in the neck or legs.
“The idea here is if you know what happens in the highest-risk individuals, you will know how to use the drugs in people at lower risk,” Nissen said. “We will have 10 times the statistical power of any trial ever done of these drugs.”
Pfizer will fund the study, expected to cost more than $100 million, but independent researchers will collect and control the results and have offered to make all of them public, not just bottom-line conclusions. No top researchers can have financial ties to any pain drug manufacturers.
“This is a very interesting model” for a public-private partnership to do medical research, said Dr. Elizabeth Nabel, director of the National Heart, Lung and Blood Institute, which will appoint a representative to serve on the study’s executive committee.
“We believe this is an effective and appropriate way to conduct this study,” said Pfizer spokeswoman Mariann Caprino.
The study will be called PRECISION, for Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen or Naproxen.
Celebrex sales have shriveled since Vioxx and Bextra were withdrawn and two studies linked it to heart attacks. For the nine months ended Sep. 30, Celebrex sales plummeted 45 percent to $1.3 billion.
Dr. Alastair Wood, a Vanderbilt University physician who heads the FDA’s non-prescription drug advisory panel, called the study “a good idea.”
“One of the underlying assumptions is that naproxen is safest,” but that has not been rigorously tested, he said.
Nissen also has served on FDA drug advisory panels and chaired one on the cox-2 drugs. He is president-elect of the American College of Cardiology, and he another Cleveland Clinic cardiologist, Dr. Eric Topol, were among the first to publish warnings about Vioxx’s safety.
On Monday, a mistrial was declared in the third lawsuit against Merck alleging the drugmaker withheld information on the drug’s problems. Merck won one and lost one of the previous trials.
