The study, “Efficacy of 1, 5, and 20 mg oral sildenafil in the treatment of adults with pulmonary arterial hypertension: a randomized, double-blind study with open-label extension.” appeared in the journal BMC Pulmonary Medicine.
A previous study had shown that Revatio (20, 40, and 80 mg, three times daily) improved the six-minute walk distance (6MWD; a test for exercise capacity) in a similar way in patients with pulmonary arterial hypertension (PAH), which led to the approval of the 20 mg dosage. This new trial (NCT00430716) aimed to find out whether lower doses of the drug were less effective than the 20 mg dosage.
Researchers located at 34 centers in the United States, Brazil, Russia and various European and Asian sites randomly gave 129 PAH patients Revatio 1, 5, or 20 mg three times a day, for 12 weeks. Patients who completed the study’s double-blind phase continued for an additional 12-week, open-label extension in which they received Revatio 20 mg three times a day.
The study’s primary endpoint was to measure changes in the 6MWD for each dose analyzed. Secondary objectives included assessing the safety and tolerability of low-dose Revatio during the 12 weeks of treatment and evaluation of its effects on perceived PAH-progression biomarkers.
Researchers prematurely terminated their study, though results showed that 12 weeks of treatment with 20 mg Revatio provided a significantly greater 6MWD improvement compared to 1 mg, but not to 5 mg. Overall, changes in hemodynamic parameters were small and variable among groups, and patients treated with Revatio 20 mg showed greater improvement in PAH biomarkers than those receiving lower dosages.
After 24 weeks, 6MWD improvement was higher in patients initially randomized to 20 versus 5 or 1 mg of Revatio.
“Despite this study having the limitation of premature termination, sildenafil 1 mg [three times a day], but not 5 mg [three times a day], was shown to be inferior to 20 mg [three times a day] for improvement in 6MWD in patients with PAH,” researchers wrote. “Sildenafil 5 mg [three times a day] appeared to have similar clinical and hemodynamic effects as 20 mg [three times a day]. Interestingly, 6MWD results from the open-label phase of the study suggest that patients on the approved sildenafil dose (20 mg [three times a day]) continued to show clinical improvement after the first 12 weeks of treatment.”
“Hence, the question remains whether doses lower than 20 mg [three times a day] have therapeutic value and needs to be seen in light of the current therapeutic approach in PAH,” the team concluded.