Inhaled Treprostinil in Pulmonary Hypertension Due to COPD: PERFECT study results


Introduction: Pulmonary hypertension accompanying chronic obstructive pulmonary disease (PH-COPD) is associated with worse outcomes than COPD alone. There are currently no approved therapies to treat PH-COPD. The PERFECT study (NCT03496623) sought to evaluate the safety and efficacy of inhaled treprostinil (iTRE) in this patient population.

Methods: Patients with PH-COPD (mean pulmonary artery pressures ≥30 mmHg and pulmonary vascular resistances ≥4 Wood units) were enrolled in a multicentre, randomised (1:1), double-blind, placebo-controlled, 12-week, crossover study. A contingent parallel design was also prespecified and implemented, based on a blinded interim analysis of missing data. Patients received treatment with iTRE up to 12 breaths (72 μg) 4 times daily or placebo. The primary efficacy end point was change in peak 6-minute walk distance (6MWD) at Week 12.

Results: In total, 76 patients were randomised, 64 in the original crossover design and 12 in the contingent parallel design; 66 patients received iTRE and 58 received placebo. The study was terminated early at the recommendation of the Data and Safety Monitoring Committee based on the totality of evidence that iTRE increased the risk of serious adverse events and suggestive evidence of an increased risk of mortality. The change in 6MWD was numerically worse with iTRE exposure than with placebo exposure.

Conclusions: The risk-benefit observations associated with iTRE in patients with PH-COPD did not support continuation of the PERFECT study. The results of this study do not support iTRE as a viable treatment option in patients with PH-COPD.