Macitentan for the treatment of inoperable chronic thromboembolic pulmonary hypertension (MERIT-1): results from the multicentre, phase 2, randomised, double-blind, placebo-controlled study

Hossein Ardeschir Ghofrani, Gérald Simonneau, Andrea M. D'Armini, Peter Fedullo, Luke S. Howard, Xavier Jaïs, David P. Jenkins, Zhi Cheng Jing, Michael M. Madani, Nicolas Martin, Eckhard Mayer, Kelly Papadakis, Dominik Richard, Nick H. Kim, Irene Lang, Christian Kähler, Marion Delcroix, Zoheir Bshouty, Pablo Sepulveda Varela, Zhi Cheng JingYuanhua Yang, Jinming Liu, Gangcheng Zhang, Nuofu Zhang, Yuhong Mi, Xianyang Zhu, Pavel Jansa, Xavier Jaïs, Grégoire Prévot, Hélène Bouvaist, Olivier Sanchez, Friedrich Grimminger, Matthias Held, Heinrike Wilkens, Stephan Rosenkranz, Ekkehard Grünig, Kristóf Karlócai, András Temesvári, Istvan Edes, Sigita Aidietienė, Skaidrius Miliauskas, Tomas Rene Pulido Zamudio, Carlos Jerjes Sanchez, Anton Vonk Noordegraaf, Jerzy Lewczuk, Piotr Podolec, Jarosław Kasprzak, Tatiana Mularek-Kubzdela, Ryszard Grzywna, Keertan Dheda, Olga Moiseeva, Alexander Chernyavskiy, Vladimir Shipulin, Olga Barbarash, Tamila Martynyuk, Hyung Kwan Kim, Jun Bean Park, Jae Seung Lee, Rudolf Speich, Silvia Ulrich, John David Aubert, Arintaya Phrommintikul, Nattapong Jaimchariyatam, Suree Sompradeekul, Zeynep Pinar Onen, Gulfer Okumus, Lyubomyr Solovey, Volodymyr Gavrysyuk, Luke Howard, Joanna Pepke-Zaba, Robin Condliffe, John McConnell, Kim Kerr, Lan Hieu Nguyen, Nguyen Vinh Pham

Research output: Contribution to journalArticle

Abstract

Background Macitentan is beneficial for long-term treatment of pulmonary arterial hypertension. The microvasculopathy of chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension are similar. Methods The phase 2, double-blind, randomised, placebo-controlled MERIT-1 trial assessed macitentan in 80 patients with CTEPH adjudicated as inoperable. Patients identified as WHO functional class II–IV with a pulmonary vascular resistance (PVR) of at least 400 dyn·s/cm5 and a walk distance of 150–450 m in 6 min were randomly assigned (1:1), via an interactive voice/web response system, to receive oral macitentan (10 mg once a day) or placebo. Treatment with phosphodiesterase type-5 inhibitors and oral or inhaled prostanoids was permitted for WHO functional class III/IV patients. The primary endpoint was resting PVR at week 16, expressed as percentage of PVR measured at baseline. Analyses were done in all patients who were randomly assigned to treatment; safety analyses were done in all patients who received at least one dose of the study drug. This study is registered with ClinicalTrials.gov, number NCT02021292. Findings Between April 3, 2014, and March 17, 2016, we screened 186 patients for eligibility at 48 hospitals across 20 countries. Of these, 80 patients in 36 hospitals were randomly assigned to treatment (40 patients to macitentan, 40 patients to placebo). At week 16, geometric mean PVR decreased to 73·0% of baseline in the macitentan group and to 87·2% in the placebo group (geometric means ratio 0·84, 95% CI 0·70–0·99, p=0·041). The most common adverse events in the macitentan group were peripheral oedema (9 [23%] of 40 patients) and decreased haemoglobin (6 [15%]). Interpretation In MERIT-1, macitentan significantly improved PVR in patients with inoperable CTEPH and was well tolerated. Funding Actelion Pharmaceuticals Ltd.

Original languageEnglish
Pages (from-to)785-794
Number of pages10
JournalThe Lancet Respiratory Medicine
Volume5
Issue number10
DOIs
Publication statusPublished - Oct 1 2017

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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