Hossein-Ardeschir Ghofrani1, Gérald Simonneau2, Andrea M D'Armini3, Peter Fedullo4, Luke S Howard5, Xavier Jaïs2, David P Jenkins6, Zhi-Cheng Jing7, Michael M Madani8, Nicolas Martin9, Eckhard Mayer10, Kelly Papadakis9, Dominik Richard9, Nick H Kim4. 1. German Center for Lung Research (DZL), Giessen, Germany; University of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany; Department of Medicine, Imperial College London, London, UK. Electronic address: ardeschir.ghofrani@innere.med.uni-giessen.de. 2. Assistance Publique-Hôpitaux de Paris, Service de Pneumologie, Hôpital Bicêtre, Université Paris-Sud, Laboratoire d'Excellence en Recherche sur le Médicament et Innovation Thérapeutique, Le Kremlin-Bicêtre, France; INSERM U-999, Le Kremlin-Bicêtre, France. 3. Department of Cardio-Thoracic and Vascular Surgery, Heart and Lung Transplantation and Pulmonary Hypertension Unit, Foundation IRCCS Policlinico San Matteo, University of Pavia School of Medicine, Pavia, Italy. 4. Division of Pulmonary and Critical Care Medicine, University of California San Diego, La Jolla, CA, USA. 5. National Pulmonary Hypertension Service, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, UK; National Heart & Lung Institute, Imperial College London, London, UK. 6. Department of Cardiothoracic Surgery, Papworth Hospital, Cambridge, UK. 7. State Key Lab of Cardiovascular Disease, FuWai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. 8. Division of Cardiovascular and Thoracic Surgery, University of California San Diego Medical Center, San Diego, CA, USA. 9. Actelion Pharmaceuticals, Allschwil, Switzerland. 10. Department of Thoracic Surgery, Kerckhoff-Clinic, Bad Nauheim, Germany.
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 phosphodiesterasetype-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.
RCT Entities:
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.
Authors: James C Coons; Kristen Pogue; Andrew R Kolodziej; Glenn A Hirsch; Marjorie Patricia George Journal: Curr Cardiol Rep Date: 2019-11-22 Impact factor: 2.931