Oral Treprostinil for the Treatment of Pulmonary Arterial Hypertension in Patients on Background Endothelin Receptor Antagonist and/or Phosphodiesterase Type 5 Inhibitor Therapy (The FREEDOM-C Study): A Randomized Controlled Trial
Tapson VF et al. – The primary endpoint of improvement in 6MWD at week 16 did not achieve significance. This study enhanced understanding of oral treprostinil titration and dosing which has set the stage for additional studies.Methods
- A 16-week, multicenter, double-blind, placebo-controlled study was conducted in 350 patients with PAH randomized to placebo or oral treprostinil.
- All patients were stable on background ERA, PDE-5I, or both.
- Primary endpoint was Hodges-Lehmann placebo-corrected median difference in change from baseline 6-minute walk distance (6MWD) at week 16.
- Secondary endpoints included time to clinical worsening, change in World Health Organization functional class, Borg dyspnea score, and dyspnea fatigue index score.
- Thirty-nine patients (22%) receiving oral treprostinil and 24 patients (14%) receiving placebo discontinued the study.
- Placebo-corrected median difference in change from baseline 6MWD at week 16 was 11 m (P=0.07).
- Improvements in dyspnea fatigue index score (P=0.01) and combined 6MWD and Borg dyspnea score (P=0.01) were observed with oral treprostinil versus placebo treatment.
- Patients who achieved a week-16 twice-daily oral treprostinil dose of 1.25-3.25 mg and 3.5-16 mg experienced a greater change in 6MWD (18 and 34 m, respectively) than patients who achieved a twice-daily dose of <1 mg or discontinued because of adverse events (4 m).