马西替坦治疗不可手术的慢性血栓栓塞性肺动脉高压（MERIT-1）：来自多中心、2 期、随机、双盲、安慰剂对照研究的结果。
Macitentan for the treatment of inoperable chronic thromboembolic pulmonary hypertension (MERIT-1): results from the multicentre, phase 2, randomised, double-blind, placebo-controlled study.
机构信息
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.
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.
出版信息
Lancet Respir Med. 2017 Oct;5(10):785-794. doi: 10.1016/S2213-2600(17)30305-3. Epub 2017 Sep 11.
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 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.
背景
马西替坦有益于肺动脉高压的长期治疗。慢性血栓栓塞性肺动脉高压（CTEPH）和肺动脉高压的微血管病变相似。
方法
这项 2 期、双盲、随机、安慰剂对照的 MERIT-1 试验评估了马西替坦在 80 名被判定为不可手术的 CTEPH 患者中的疗效。通过交互式语音/网络应答系统，将具有 WHO 功能分类 II-IV 级、肺血管阻力（PVR）至少为 400 dyn·s/cm 和 6 分钟步行距离为 150-450m 的患者随机分配（1:1），分别接受马西替坦（10mg，每天 1 次）或安慰剂治疗。允许 WHO 功能分类 III/IV 级患者使用磷酸二酯酶 5 抑制剂和口服或吸入前列环素。主要终点为第 16 周静息时的 PVR，以基线时测量的 PVR 的百分比表示。所有随机接受治疗的患者均进行了分析；所有接受至少一剂研究药物的患者均进行了安全性分析。本研究在 ClinicalTrials.gov 注册，编号为 NCT02021292。
结果
2014 年 4 月 3 日至 2016 年 3 月 17 日，我们在 20 个国家的 48 家医院筛选了 186 名符合条件的患者。其中，36 家医院的 80 名患者被随机分配到治疗组（马西替坦组 40 例，安慰剂组 40 例）。第 16 周时，马西替坦组 PVR 几何均数降至基线的 73.0%，安慰剂组降至 87.2%（几何均数比值 0.84，95%CI 0.70-0.99，p=0.041）。马西替坦组最常见的不良事件为外周水肿（40 例患者中有 9 例[23%]）和血红蛋白降低（6 例[15%]）。
解释
在 MERIT-1 中，马西替坦显著改善了不可手术的 CTEPH 患者的 PVR，且耐受性良好。
资金来源
Actelion Pharmaceuticals Ltd.
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