Efficacy and Safety of Oral Treprostinil Monotherapy for the Treatment of Pulmonary Arterial Hypertension: A Randomized Controlled Trial
Background—Pulmonary arterial hypertension (PAH) is a progressive, fatal disease with no cure. Parenteral and inhaled prostacyclin analogue therapies are effective for the treatment of PAH but complicated administration requirements can limit the use of these therapies in patients with less severe disease. This study was designed to evaluate the safety and efficacy of the oral prostacyclin analogue, treprostinil diolamine, as initial treatment for de novo PAH.
Methods and Results—Three hundred and forty-nine patients (intent-to-treat population [ITT]) not receiving endothelin receptor antagonist or phosphodiesterase type-5 inhibitor background therapy were randomized (treprostinil, n=233; placebo, n=116). The primary analysis population (modified ITT [mITT]) included 228 patients (treprostinil, n=151; placebo, n=77) with access to 0.25 mg treprostinil tablets at randomization. The primary endpoint was change from baseline in 6-minute walk distance (6MWD) at week 12. Secondary endpoints included Borg dyspnea index, clinical worsening, and symptoms of PAH. The week 12 treatment effect for 6MWD (mITT population) was 23.0 m (p=0.0125). For the ITT population, 6MWD improvements were observed at peak (26.0 m; p=0.0001) and trough plasma study drug concentrations (17.0 m; p=0.0025). Other than an improvement in the combined 6MWD/Borg dyspnea score, there were no significant changes in secondary endpoints. Oral treprostinil therapy was generally well-tolerated; most common adverse events (ITT) were headache (69%), nausea (39%), diarrhea (37%), and pain in jaw (25%).
Conclusions—Oral treprostinil improves exercise capacity in PAH patients not receiving other treatment. Oral treprostinil could provide a convenient, first-line prostacyclin treatment option for PAH patients not requiring more intensive therapy.
Clinical Trial Registration—ClinicalTrials.gov; Unique Identifier: NCT00325403.
- Received June 19, 2012.
- Accepted December 17, 2012.
- Copyright © 2013, Circulation