1. Macitentan for the treatment of inoperable chronic thromboembolic pulmonary hypertension (MERIT-1):results from the multicentre, phase 2, randomised, double-blind, placebo-controlled study
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András Temesvári, Sigita Aidietienė, Vladimir M. Shipulin, Jae Seung Lee, Pavel Jansa, Nuofu Zhang, Dominik Richard, Nguyen Vinh Pham, Carlos Jerjes Sanchez, Lan Hieu Nguyen, Keertan Dheda, Christian M. Kähler, Olga Barbarash, Piotr Podolec, Tomas Rene Pulido Zamudio, Michael M. Madani, Hyung Kwan Kim, Suree Sompradeekul, Grégoire Prévot, Silvia Ulrich, Luke Howard, Nattapong Jaimchariyatam, Olga Moiseeva, Gulfer Okumus, Zoheir Bshouty, Arintaya Phrommintikul, Friedrich Grimminger, David P. Jenkins, Heinrike Wilkens, Robin Condliffe, Irene Lang, John-David Aubert, Rudolf Speich, Tatiana Mularek-Kubzdela, Nicolas Martin, Hélène Bouvaist, Stephan Rosenkranz, Jun Bean Park, Peter F. Fedullo, Luke S. Howard, Olivier Sanchez, Gérald Simonneau, Ryszard Grzywna, Alexander Chernyavskiy, Zhi-Cheng Jing, Joanna Pepke-Zaba, Anton Vonk Noordegraaf, Andrea Maria D'Armini, Pablo Sepulveda Varela, Gang-Cheng Zhang, Nick H. Kim, Eckhard Mayer, Jerzy Lewczuk, Yuhong Mi, Zeynep Pinar Onen, Ekkehard Grünig, Xian-Yang Zhu, Marion Delcroix, John McConnell, Yuanhua Yang, Jin-Ming Liu, Lyubomyr Solovey, Kelly Papadakis, Xavier Jaïs, Istvan Edes, Tamila Vitalievna Martynyuk, Matthias Held, Kristóf Karlócai, Jarosław Kasprzak, Skaidrius Miliauskas, Hossein Ardeschir Ghofrani, Kim M. Kerr, Volodymyr Gavrysyuk, ACS - Pulmonary hypertension & thrombosis, Pulmonary medicine, and APH - Quality of Care
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Endothelin Receptor Antagonists ,Male ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Hypertension, Pulmonary ,Placebo-controlled study ,030204 cardiovascular system & hematology ,Placebo ,law.invention ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Double-Blind Method ,Randomized controlled trial ,law ,Internal medicine ,Natriuretic Peptide, Brain ,medicine ,Clinical endpoint ,Humans ,Aged ,Macitentan ,Sulfonamides ,business.industry ,Middle Aged ,medicine.disease ,Pulmonary hypertension ,Peptide Fragments ,Pulmonary embolism ,Surgery ,Clinical trial ,Pyrimidines ,Treatment Outcome ,030228 respiratory system ,chemistry ,Chronic Disease ,Female ,Vascular Resistance ,Pulmonary Embolism ,business - Abstract
Summary 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/cm 5 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.
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- 2017
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