Two studies comparing subcutaneous trepostinil and placebo were included in a Cochrane review . A 12-week multicenter RCT included 470 subjects (mainly NYHA functional class III) with pulmonary arterial hypertension, either primary or associated with connective tissue disease or congenital systemic-to-pulmonary shunts. The other study was a 8-week pilot study including 23 subjects (mainly NYHA III) with primary pulmonary artery hypertension. The larger study showed that exercise capacity improved with treprostinil and was unchanged with placebo; the between treatment group difference in median six-minute walking distance (6-MWD) was 16 m (p = 0.006). Improvement in exercise capacity was greater in the sicker patients and was dose-related, but independent of disease etiology. The other study reported no significant difference in mean change from baseline scores between treprostinil and placebo. Effect on NYHA functional class was not reported in either study. There was a significant difference in mean change of pulmonary artery pressure from baseline in favour of treprostinil of -2.71 mmHg (95% CI -4.2, -1.23). However there was considerable statistical heterogeneity between the two studies (I2=57.6%). In the larger study, treprostinil significantly improved indices of dyspnea, and signs and symptoms of pulmonary hypertension. The other study reported non-significant differences in the Borg Dyspnoea Score and Dyspnoea Fatigue Rating.
Infusion site pain was more common with treprostinil compared with placebo (OR 17.32, 95% CI 10.96 to 27.39), as was the likelihood of withdrawing due to drug-related adverse events (OR 13.47, 95% CI 2.57 to 70.48). In the larger study, 85% of patients in treprostonil group had infusion site pain leading to premature discontinuation from the study in 8% of patients. Three patients in the treprostinil group had an episode of gastrointestinal hemorrhage.
Comment: The quality of evidence is downgraded by study quality (unclear allocation concealment).