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Randomized Controlled Trial
. 2024 Jun 6;63(6):2400172.
doi: 10.1183/13993003.00172-2024. Print 2024 Jun.

Inhaled treprostinil in pulmonary hypertension associated with COPD: PERFECT study results

Steven D Nathan  1 , Rahul Argula  2 , Maria G Trivieri  3 , Sameh Aziz  4 , Elizabeth Gay  5 , Boris Medarov  6 , Joseph Parambil  7 , Amresh Raina  8 , Michael G Risbano  9 , Thenappan Thenappan  10 , Jose Soto Soto  11 , Heidi Bell  12 , Victoria Lacasse  13 , Prakash Sista  13 , Michael Di Marino  13 , Aimee Smart  13 , Brittanie Hawkes  13 , Elizabeth Nelson  13 , Todd Bull  14 , Victor Tapson  15 , Aaron Waxman  5
Affiliations
Randomized Controlled Trial

Inhaled treprostinil in pulmonary hypertension associated with COPD: PERFECT study results

Steven D Nathan et al. Eur Respir J. .

Abstract

Background: Pulmonary hypertension (PH) accompanying COPD (PH-COPD) is associated with worse outcomes than COPD alone. There are currently no approved therapies to treat PH-COPD. The PERFECT study (ClinicalTrials.gov: NCT03496623) evaluated the safety and efficacy of inhaled treprostinil (iTRE) in this patient population.

Methods: Patients with PH-COPD (mean pulmonary arterial pressure ≥30 mmHg and pulmonary vascular resistance ≥4 WU) 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-min 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.

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Conflict of interest statement

Conflict of interest: S.D. Nathan is a paid consultant for United Therapeutics. R.G. Argula reports advisory board consulting fees from United Therapeutics, Liquidia Inc., Merck Pharmaceuticals, Janssen and Accordant Health (CVS), and lecture honoraria from United Therapeutics, outside the submitted work. M.G. Trivieri reports advisory board participation with Janssen, outside the submitted work. B. Medarov reports lecture honoraria from Jensen Pharmaceuticals, outside the submitted work. A. Raina reports lecture honoraria from Merck and United Therapeutics, outside the submitted work. M.G. Risbano reports grants from Shadyside Foundation, royalties from Springer (Pulmonary Hypertension: Controversial and Emerging Topics), and advisory board participation with Gilead and Liquidia, outside the submitted work. T. Thenappan reports grants from United Therapeutics, Aerovate, Merck and Aria CV, and consulting fees from Merck and United Therapeutics, outside the submitted work. J.S. Soto reports grants, lecture honoraria, travel support and advisory board participation with GlaxoSmithKline and Genentech Pharmaceuticals, outside the submitted work. H. Bell, V. Lacasse, P. Sista, M. Di Marino, A. Smart, B. Hawkes and E. Nelson are employees of United Therapeutics, the PERFECT study sponsor. T. Bull reports grants from Bayer, Merck, Insmed and Aerovate, lecture honoraria from Merck, payment for expert testimony from Lung Biotechnology, travel support from Lung, advisory board participation with Keros, consultancy for United Therapeutics and a leadership role as PHA SLC chair, outside the submitted work. V. Tapson is a paid consultant for United Therapeutics. A. Waxman reports grants from Aria CV PI, AI Therapeutics and Acceleron/Merck, consultancy for United Therapeutics, and data and safety monitoring board participation with Insmed, outside the submitted work. The remaining authors have no potential conflicts of interest to disclose.

Figures

None
Overview of the PERFECT study.
FIGURE 1
FIGURE 1
Subject disposition. GOLD: Global Initiative for Chronic Obstructive Lung Disease; RHC: right heart catheterisation; PAH: pulmonary arterial hypertension; COVID-19: coronavirus disease 2019; iTRE: inhaled treprostinil.
FIGURE 2
FIGURE 2
Study design for crossover or contingency scenario. iTRE: inhaled treprostinil.
See this image and copyright information in PMC

Comment in

References

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