NHLBI stopped pulmonary hypertension drug trial in patients with sickle cell disease

Patients taking sildenafil in WALK-PHASST were significantly more likely to have serious medical problems than those on placebo.

On a recommendation from a Data Safety Monitoring Board, the National Heart, Lung, and Blood Institute stopped theWALK-PHASST trial testing sildenafil for treatment of pulmonary hypertension in adults with sickle cell disease after it became clear that patients assigned the drug had severe medical problems, including episodes of sickle cell crises.

“We will continue to look into the possible causes of these preliminary results,” said NHLBI Director Elizabeth G. Nabel, MD, in a press release. “In the meantime, we encourage patients with sickle cell disease who are taking sildenafil [Viagra, Pfizer] for pulmonary hypertension to talk with their physicians about the potential risks and benefits of the medication and what actions they should consider, including whether to taper off this medication and how to best manage both sickle cell disease and pulmonary hypertension.”

WALK-PHASST was the first multicenter, randomized clinical trial to test the safety and effectiveness of sildenafil for pulmonary hypertension in patients with sickle cell disease. Primary outcome – reduced pulmonary hypertension symptoms – was measured by six-minute walk test. Seventy-four patients were randomly assigned placebo or sildenafil for 16 weeks. At the end of the 16 weeks, patients could choose to be part of the open-label follow-up phase of the study for up to one year. When the study was stopped on July 7, 33 patients had completed the trial.

Approximately 30% of people with sickle cell disease develop pulmonary hypertension, which is associated with sudden death in this population. Nabel said that the adverse events in the trial associated with the drug among patients with sickle cell disease should not be applied to other patients.