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

被引:214
作者
Ghofrani, Hossein-Ardeschir [1 ,2 ,3 ]
Simonneau, Gerald [4 ,5 ]
D'Armini, Andrea M. [6 ]
Fedullo, Peter [7 ]
Howard, Luke S. [8 ,9 ]
Jais, Xavier [4 ,5 ]
Jenkins, David P. [10 ]
Jing, Zhi-Cheng [11 ,12 ]
Madani, Michael M. [13 ]
Martin, Nicolas [14 ]
Mayer, Eckhard [15 ]
Papadakis, Kelly [14 ]
Richard, Dominik [14 ]
Kim, Nick H. [7 ]
机构
[1] German Ctr Lung Res DZL, Giessen, Germany
[2] UGMLC, D-35392 Giessen, Germany
[3] Imperial Coll London, Dept Med, London, England
[4] Univ Paris Sud, Hop Bicetre, AP HP, Serv Pneumol,Lab Excellence Rech Medicament & Inn, Le Kremlin Bicetre, France
[5] INSERM U999, Le Kremlin Bicetre, France
[6] Univ Pavia, Sch Med, Fdn IRCCS Policlin San Matteo, Dept Cardiothorac & Vasc Surg,Heart & Lung Transp, Pavia, Italy
[7] Univ Calif San Diego, Div Pulm & Crit Care Med, La Jolla, CA 92093 USA
[8] Imperial Coll Healthcare NHS Trust, Hammersmith Hosp, Natl Pulm Hypertens Serv, London, England
[9] Imperial Coll London, Natl Heart & Lung Inst, London, England
[10] Papworth Hosp, Dept Cardiothorac Surg, Cambridge, England
[11] Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, FuWai Hosp, State Key Lab Cardiovasc Dis, Beijing, Peoples R China
[12] Peking Union Med Coll, Beijing, Peoples R China
[13] Univ Calif San Diego, Med Ctr, Div Cardiovasc & Thorac Surg, 225 Dickinson St, San Diego, CA 92103 USA
[14] Actel Pharmaceut, Allschwil, Switzerland
[15] Kerckhoff Clin, Dept Thorac Surg, Bad Nauheim, Germany
关键词
ENDARTERECTOMY; RIOCIGUAT; LESIONS;
D O I
10.1016/S2213-2600(17)30305-3
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
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 400dyn.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.
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收藏
页码:785 / 794
页数:10
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