Safety concern from side effects prompts action by U.S. government
TUESDAY, July 28 (HealthDay News) -- The first clinical trial of a treatment for pulmonary hypertension in adults with sickle cell anemia has been stopped because of severe side effects in some participants.
The trial involved sildenafil -- marketed as Viagra when it is used to treat erectile dysfunction and Revatio when used for pulmonary arterial hypertension, or high blood pressure in the lungs.
"This was a very big disappointment," said Dr. Mark Gladwin, lead investigator of the study, which was sponsored by the U.S. National Heart, Lung, and Blood Institute. "We were very excited about this drug. It has a very high safety profile and has worked in every form of pulmonary hypertension. The preliminary data showed a lowering in pulmonary hypertension in sickle cell patients."
Pulmonary hypertension affects as many as 30 percent of people with sickle cell disease. "It's the highest risk of death, so it's a very important complication," said Gladwin, who is director of the Vascular Medicine Institute at the University of Pittsburgh.
People with sickle cell disease have an average of two so-called "crises" a year, involving severe pain and often requiring hospitalization. The crises occur when red blood cells, which are misshaped in those with the disease, get jammed up in the blood vessels, blocking blood flow.
An estimated 70,000 to 100,000 people in the United States have this genetic blood disorder, most of them black.
According to the institute, there are no current guidelines for treating pulmonary hypertension in people with sickle-cell disease, although drugs known as endothelin receptor blockers are sometimes used. The condition can lead to heart failure and death.
A small pilot trial using Revatio and involving just 12 people with sickle cell anemia had found a decrease in pulmonary hypertension. But the participants were also aggressively treated with transfusions and the drug hydroxyurea to control crises.
In the multicenter trial that was stopped, 134 people were treated with Revatio but without the interventions for crises. "We wanted to test the drug in the way it would probably used in doctors' offices," Gladwin said.
When it was stopped July 7, more than a year early, 33 people had completed the trial, having received 16 weeks of treatment with Revatio or placebo. More than a third (38 percent) of those given the drug had severe side effects, mostly sickle cell pain crises, compared with 8 percent of people taking the placebo.
Researchers are now looking at the efficacy of the drug: Did it actually have any effect, positive or negative, on pulmonary hypertension? If there were positive effects, the researchers said, there may be other ways it could be used.
"It may be that we could use the drug in patients whose pain is controlled with either transfusions or hydroxyurea, although it's possible that the risk-benefit ratio would only play out in patients with higher pulmonary hypertension," Gladwin said. "The patients in this trial had mild-to-moderate pulmonary hypertension."
The investigators don't know why the trial produced the increased risk for pain crises, but they said there was no indication that the drug is not safe in other populations.
Pfizer, which makes Viagra and Revatio, provided the drug as well as the placebo for the trial.
The U.S. National Heart, Lung and Blood Institute has more on sickle cell disease.
SOURCES: Mark T. Gladwin, M.D., division chief, Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh Medical Center, and director, Vascular Medicine Institute, University of Pittsburgh; U.S. National Heart, Lung and Blood Institute, news release, July 28, 2009
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