Clinical Study to Assess the Efficacy, Safety and Tolerability of Macitentan in Subjects With Inoperable Chronic Thromboembolic Pulmonary Hypertension (MERIT-1)

Prospective, Randomized, Placebo-controlled, Double-blind, Multicenter, Parallel-group, 24-week Study to Assess the Efficacy, Safety and Tolerability of Macitentan in Subjects With Inoperable Chronic Thromboembolic Pulmonary Hypertension

Study to evaluate if macitentan is efficient, safe and tolerable enough to be used for treatment of inoperable chronic thromboembolic pulmonary hypertension (CTEPH).

Study Overview

• Status: Completed
• Conditions: Chronic Thromboembolic Pulmonary Hypertension
• Intervention / Treatment: Drug: Macitentan; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • University Hospital Gasthuisberg / Interne Geneeskunde - I.G. Pneumologie
• China
  • Beijing, China, 100020
    • Beijing Chao-Yang Hospital-Department of Respiration
  • Beijing, China, 100037
    • Cardiovascular institute & Fuwai Hospital- Thrombus Center
  • Guangzhou, China, 510120
    • The first affiliated hospital of guangzhou medical university-respiratory department
  • Shanghai, China, 200433
    • ngShanghai Pulmonary Hospital, Department of Pulmonary Circulation
  • Shenyang, China, 110016
    • The General Hospital of Shenyang Military Region,Congenital Heart Disease Department
  • Wuhan, China, 430022
    • Wuhan Asia Heart Hospital
• Czechia
  • Praha, Czechia, 128 08
    • Centre for PPH, Charles University , II Interni klinika1.LF a VFN
• France
  • Le Kremlin-Bicêtre cedex, France, 94275
    • CHU de Bicêtre
  • Paris cedex 15, France, 75908
    • Hôpital Européen Georges Pompidou Service de Pneumologie, soins intensifs et endoscopies bronchiques
  • Toulouse Cedex 9, France, 31059
    • CHU de Toulouse Hopital Larrey
• Germany
  • Giessen, Germany, 35392
    • Justus-Liebig-Universität Gießen
  • Heidelberg, Germany, 69126
    • Thoraxklinik am Universitatsklinikum Heidelberg
  • Würzburg, Germany, 97074
    • Missionsärztliche Klinik gGmbH Akademisches Lehrkrankenhaus der Julius-Maximilians-Universität
• Hungary
  • Budapest, Hungary, 1125
    • Semmelweis Egyetem
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem Orvos- és Egészségtudományi Centrum, Kardiológiai Klinika
• Korea, Republic of
  • Seoul, Korea, Republic of, 3722
    • Severance Hospital, Yonsei University Health System
• Lithuania
  • Kaunas, Lithuania, 50161
    • Lietuvos Sveikatos Mokslų Universiteto Ligoninės Kauno Klinikos Pulmonologijos-Imunologijos Klinika
• Mexico
  • Mexico City, Mexico, 14080
    • Instituto Nacional de Cardiologia (INC) Ignacio Chavez
• Poland
  • Lublin, Poland, 20-718
    • Wojewódzki Szpital Specjalistyczny w Lublinie im. Stefana Kardynała Wyszyńskiego SPZOZ Oddział Kardiologii - Pododdział Intensywnego Nadzoru Kardiologicznego
  • Wrocaw, Poland, 51-124
    • Wojewódzki Szpital Specjalistyczny we Wrocawiu
• Russian Federation
  • Kemerovo, Russian Federation, 650002
    • Federal State Budgetary Institution "Scientific Research Institute of Systemic Problems of Cardiovascular Diseases", Siberian branch of RAMS
  • Moscow, Russian Federation, 121552
    • Federal State Budgetary Institution "Russian Cardiology Scientific and Production Complex" of the Ministry of Health Care of the Russian Federation
  • Novosibirsk, Russian Federation, 630055
    • E.N.Meshalkin Novosibirsk State Research Institute Of Circulation Pathology Rosmedtechnology
  • St. Petersburg, Russian Federation, 197341
    • Federal State Institution "Federal center of Heart, Blood and Endocrinology named after V.A.Almazov Rosmedtekhnologies"
  • Tomsk, Russian Federation, 634012
    • Federal State Budgetary Institution "Research Institute for Cardiology" of Siberian Branch under the Russian Academy of Medical Sciences / Cardiovascular Surgery Department
• Switzerland
  • Zürich, Switzerland, 8091
    • University Hospital Zurich
• Thailand
  • Bangkok, Thailand, 10330
    • King Chulalongkorn Memorial Hospital, Division of Respiratory and Respiratory Critical Care Medicine
  • Bangkok, Thailand, 10700
    • Siriraj Hospital, Division of Respiratory Disease and Tuberculosis
  • Chiang Mai, Thailand, 50200
    • MAHARAJ NAKORN CHIANG MAI HOSPITAL, Department of Internal Medicine
• Turkey
  • Capa_Istanbul, Turkey, 34093
    • Istanbul University İstanbul Faculty Medicine Pulmonology Department
• Ukraine
  • Kyiv, Ukraine, 03680
    • State Institute Of Phthisiology And Pulmonology N.A. F.G. Yanovskiy Of Ams Ukraine
  • Lviv, Ukraine, 79014
    • Lviv Regional Clinical Hospital, Cardiosurgery Department
• United Kingdom
  • Cambridge, United Kingdom, CB23 3RE
    • Papworth Hospital NHS Trust, Pulmonary Vascular Diseases Unit
  • London, United Kingdom, W12 0HS
    • Hammersmith Hospital
  • Sheffield, United Kingdom, S10 2RX
    • Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital, Pulmonary Vascular Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 84 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Written informed consent
• Subject with CTEPH (WHO Group 4) judged as inoperable due to the localization of the obstruction being surgically inaccessible (i.e., distal disease).
• Female of childbearing potential must have a negative pre-treatment serum pregnancy test, be advised on appropriate methods of contraception, and agree to use 2 reliable methods of contraception.

Exclusion Criteria:

• Previous pulmonary endarterectomy.
• Recurrent thromboembolism despite sufficient oral anticoagulants.
• Symptomatic acute pulmonary embolism in the 6-month period prior to randomization.
• Known moderate-to-severe restrictive lung disease (i.e., TLC < 60% of predicted value) or obstructive lung disease (i.e., FEV1 < 70% of predicted, with FEV1/FVC < 65%) or known significant chronic lung disease diagnosed by chest imaging (e.g., interstitial lung disease, emphysema).
• Acute or chronic conditions (other than dyspnea) that limit the ability to comply with study requirements in the 3-month period prior to Screening visit or during the Screening period.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Macitentan; Macitentan 10 mg, oral tablet, to be taken once daily.	Drug: Macitentan; Macitentan 10 mg, oral tablet, to be taken once daily.; Other Names: ACT-064992
Placebo Comparator: Placebo; Matching placebo oral tablet, to be taken once daily.	Drug: Placebo; Matching placebo oral tablet, to be taken once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 16 in Pulmonary Vascular Resistance (PVR) at Rest.	The primary efficacy endpoint is defined as the PVR at rest at Week 16 expressed as percent of baseline PVR at rest.	From baseline to Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 24 in Exercise Capacity, as Measured by the 6-minute Walk Distance (6MWD).	The purpose of the six minute walk is to test exercise tolerance and capacity. The test measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes.	From baseline to Week 24
Change From Baseline to Week 24 in Borg Dyspnea Index Collected at the End of the 6-minute Walk Test (6MWT).	This outcome measures the difference in the Borg dyspnea index collected at the end of the 6-minute walk test (6MWT) at Week 24 compared to baseline. The Borg dyspnea index rates the severity of dyspnea (difficult or labored breathing) on a scale from 0 ('Nothing at all') to 10 ('Very, very severe - maximal'). A decrease in the Borg dyspnea index indicates an improvement.	From baseline to Week 24
Proportion of Subjects With Worsening in WHO Functional Class (FC) From Baseline to Week 24	WHO functional classes are defined as follows: 1) class I: no symptoms with exercise or at rest. No limitation of activity. 2) class II: No symptoms at rest but slight limitation with ordinary activities causing symptoms (e.g. short of breath with climbing a flight of stairs, grocery shopping, or making the bed). 3) class III: may not have symptoms at rest but activities greatly limited by shortness of breath, fatigue, or near fainting. 4) class IV: symptoms at rest (such as dyspnea and/or fatigue) and inability to carry out any physical activity without symptoms (e.g. may faint especially while bending over with their heads lowered). Patients in class IV manifest signs of right heart failure. Shifting to a higher class (e.g. from class III to class IV) represents a 'worsening' while shifting to a lower class (e.g. from class III to class II) means an 'improvement'.	From baseline to Week 24

Collaborators and Investigators

• Sponsor: Actelion
• Investigators: Study Chair: Kelly Papadakis, MD, Actelion

Publications and helpful links

General Publications

• Ghofrani HA, Simonneau G, D'Armini AM, Fedullo P, Howard LS, Jais X, Jenkins DP, Jing ZC, Madani MM, Martin N, Mayer E, Papadakis K, Richard D, Kim NH; MERIT study investigators. Macitentan for the treatment of inoperable chronic thromboembolic pulmonary hypertension (MERIT-1): results from the multicentre, phase 2, randomised, double-blind, placebo-controlled study. Lancet Respir Med. 2017 Oct;5(10):785-794. doi: 10.1016/S2213-2600(17)30305-3. Epub 2017 Sep 11.

Study record dates

Study Major Dates

• Study Start (Actual): August 20, 2014
• Primary Completion (Actual): September 28, 2016
• Study Completion (Actual): September 28, 2016

Study Registration Dates

• First Submitted: December 20, 2013
• First Submitted That Met QC Criteria: December 20, 2013
• First Posted (Estimate): December 27, 2013

Study Record Updates

• Last Update Posted (Actual): June 4, 2020
• Last Update Submitted That Met QC Criteria: May 25, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Chronic thromboembolic pulmonary hypertension (CTEPH)
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Hypertension, Pulmonary; Molecular Mechanisms of Pharmacological Action; Endothelin Receptor Antagonists; Endothelin A Receptor Antagonists; Endothelin B Receptor Antagonists; Macitentan
• Other Study ID Numbers: AC-055E201