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

Autor:	Nathan SD; Inova Fairfax Hospital, Falls Church, VA, USA steven.nathan@inova.org., Argula R; Medical University of South Carolina, Charleston, SC, USA., Trivieri MG; Division of Cardiology, Icahn School of Medicine, Mount Sinai Hospital, New York, NY, USA., Aziz S; Carilion Clinic, VTC School of Medicine, Roanoke, VA, USA., Gay E; Brigham and Women's Hospital, Boston, MA, USA., Medarov B; Albany Medical Center, Albany, NY, USA., Parambil J; Cleveland Clinic, Cleveland, OH, USA., Raina A; Allegheny General Hospital, Pittsburgh, PA, USA., Risbano MG; University of Pittsburgh Medical Center, Pittsburgh, PA, USA., Thenappan T; University of Minnesota Medical Center, Minneapolis, MN, USA., Soto JS; Ascension St Vincent's Southside Hospital, Jacksonville, FL, USA., Bell H; United Therapeutics, Research Triangle Park, NC, USA., Lacasse V; United Therapeutics, Silver Spring, MD, USA., Sista P; United Therapeutics, Silver Spring, MD, USA., Di Marino M; United Therapeutics, Silver Spring, MD, USA., Smart A; United Therapeutics, Silver Spring, MD, USA., Hawkes B; United Therapeutics, Silver Spring, MD, USA., Nelson E; United Therapeutics, Silver Spring, MD, USA., Bull T; University of Colorado, Denver, CO, USA., Tapson V; Cedars Sinai Medical Center, Los Angeles, CA, USA., Waxman A; Brigham and Women's Hospital, Boston, MA, USA.
Jazyk:	angličtina
Zdroj:	The European respiratory journal [Eur Respir J] 2024 Jun 06; Vol. 63 (6). Date of Electronic Publication: 2024 Jun 06 (Print Publication: 2024).
DOI:	10.1183/13993003.00172-2024
Abstrakt:	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. Competing Interests: 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. (Copyright ©The authors 2024.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu