TY - JOUR
T1 - Macitentan for the treatment of inoperable chronic thromboembolic pulmonary hypertension (MERIT-1)
T2 - results from the multicentre, phase 2, randomised, double-blind, placebo-controlled study
AU - MERIT study investigators
AU - Ghofrani, Hossein Ardeschir
AU - Simonneau, Gérald
AU - D'Armini, Andrea M.
AU - Fedullo, Peter
AU - Howard, Luke S.
AU - Jaïs, Xavier
AU - Jenkins, David P.
AU - Jing, Zhi Cheng
AU - Madani, Michael M.
AU - Martin, Nicolas
AU - Mayer, Eckhard
AU - Papadakis, Kelly
AU - Richard, Dominik
AU - Kim, Nick H.
AU - Lang, Irene
AU - Kähler, Christian
AU - Delcroix, Marion
AU - Bshouty, Zoheir
AU - Varela, Pablo Sepulveda
AU - Jing, Zhi Cheng
AU - Yang, Yuanhua
AU - Liu, Jinming
AU - Zhang, Gangcheng
AU - Zhang, Nuofu
AU - Mi, Yuhong
AU - Zhu, Xianyang
AU - Jansa, Pavel
AU - Jaïs, Xavier
AU - Prévot, Grégoire
AU - Bouvaist, Hélène
AU - Sanchez, Olivier
AU - Grimminger, Friedrich
AU - Held, Matthias
AU - Wilkens, Heinrike
AU - Rosenkranz, Stephan
AU - Grünig, Ekkehard
AU - Karlócai, Kristóf
AU - Temesvári, András
AU - Edes, Istvan
AU - Aidietienė, Sigita
AU - Miliauskas, Skaidrius
AU - Zamudio, Tomas Rene Pulido
AU - Sanchez, Carlos Jerjes
AU - Noordegraaf, Anton Vonk
AU - Lewczuk, Jerzy
AU - Podolec, Piotr
AU - Kasprzak, Jarosław
AU - Mularek-Kubzdela, Tatiana
AU - Grzywna, Ryszard
AU - Dheda, Keertan
PY - 2017/10/1
Y1 - 2017/10/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85028987452&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/S2213-2600(17)30305-3
DO - https://doi.org/10.1016/S2213-2600(17)30305-3
M3 - Article
SN - 2213-2600
VL - 5
SP - 785
EP - 794
JO - The Lancet Respiratory Medicine
JF - The Lancet Respiratory Medicine
IS - 10
ER -