Back to resultsClinical Study to Assess the Efficacy, Safety and Tolerability of Macitentan in Subjects With Inoperable Chronic Thromboembolic Pulmonary Hypertension (MERIT-1)
Primary Purpose
Chronic Thromboembolic Pulmonary Hypertension
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Macitentan
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Thromboembolic Pulmonary Hypertension focused on measuring Chronic thromboembolic pulmonary hypertension (CTEPH)
Eligibility Criteria
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.
Sites / Locations
- University Hospital Gasthuisberg / Interne Geneeskunde - I.G. Pneumologie
- Beijing Chao-Yang Hospital-Department of Respiration
- Cardiovascular institute & Fuwai Hospital- Thrombus Center
- The first affiliated hospital of guangzhou medical university-respiratory department
- ngShanghai Pulmonary Hospital, Department of Pulmonary Circulation
- The General Hospital of Shenyang Military Region,Congenital Heart Disease Department
- Wuhan Asia Heart Hospital
- Centre for PPH, Charles University , II Interni klinika1.LF a VFN
- CHU de Bicêtre
- Hôpital Européen Georges Pompidou Service de Pneumologie, soins intensifs et endoscopies bronchiques
- CHU de Toulouse Hopital Larrey
- Justus-Liebig-Universität Gießen
- Thoraxklinik am Universitätsklinikum Heidelberg
- Missionsärztliche Klinik gGmbH Akademisches Lehrkrankenhaus der Julius-Maximilians-Universität
- Semmelweis Egyetem
- Debreceni Egyetem Orvos- és Egészségtudományi Centrum, Kardiológiai Klinika
- Severance Hospital, YonSei University Health System
- Lietuvos Sveikatos Mokslų Universiteto Ligoninės Kauno Klinikos Pulmonologijos-Imunologijos Klinika
- Instituto Nacional de Cardiologia (INC) Ignacio Chavez
- Wojewódzki Szpital Specjalistyczny w Lublinie im. Stefana Kardynała Wyszyńskiego SPZOZ Oddział Kardiologii - Pododdział Intensywnego Nadzoru Kardiologicznego
- Wojewódzki Szpital Specjalistyczny we Wrocawiu
- Federal State Budgetary Institution "Scientific Research Institute of Systemic Problems of Cardiovascular Diseases", Siberian branch of RAMS
- Federal State Budgetary Institution "Russian Cardiology Scientific and Production Complex" of the Ministry of Health Care of the Russian Federation
- E.N.Meshalkin Novosibirsk State Research Institute Of Circulation Pathology Rosmedtechnology
- Federal State Institution "Federal center of Heart, Blood and Endocrinology named after V.A.Almazov Rosmedtekhnologies"
- Federal State Budgetary Institution "Research Institute for Cardiology" of Siberian Branch under the Russian Academy of Medical Sciences / Cardiovascular Surgery Department
- University Hospital Zürich
- King Chulalongkorn Memorial Hospital, Division of Respiratory and Respiratory Critical Care Medicine
- Siriraj Hospital, Division of Respiratory Disease and Tuberculosis
- MAHARAJ NAKORN CHIANG MAI HOSPITAL, Department of Internal Medicine
- Istanbul University İstanbul Faculty Medicine Pulmonology Department
- State Institute of Phthisiology and Pulmonology n.a. F.G. Yanovskiy of AMS Ukraine
- Lviv Regional Clinical Hospital, Cardiosurgery Department
- Papworth Hospital NHS Trust, Pulmonary Vascular Diseases Unit
- Hammersmith Hospital
- Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital, Pulmonary Vascular Medicine
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Macitentan
Placebo
Arm Description
Macitentan 10 mg, oral tablet, to be taken once daily.
Matching placebo oral tablet, to be taken once daily.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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'.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02021292
Brief Title
Clinical Study to Assess the Efficacy, Safety and Tolerability of Macitentan in Subjects With Inoperable Chronic Thromboembolic Pulmonary Hypertension
Acronym
MERIT-1
Official Title
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 Type
Interventional
2. Study Status
Record Verification Date
May 2020
Overall Recruitment Status
Completed
Study Start Date
August 20, 2014 (Actual)
Primary Completion Date
September 28, 2016 (Actual)
Study Completion Date
September 28, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Actelion
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Study to evaluate if macitentan is efficient, safe and tolerable enough to be used for treatment of inoperable chronic thromboembolic pulmonary hypertension (CTEPH).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Thromboembolic Pulmonary Hypertension
Keywords
Chronic thromboembolic pulmonary hypertension (CTEPH)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
80 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Macitentan
Arm Type
Experimental
Arm Description
Macitentan 10 mg, oral tablet, to be taken once daily.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Matching placebo oral tablet, to be taken once daily.
Intervention Type
Drug
Intervention Name(s)
Macitentan
Other Intervention Name(s)
ACT-064992
Intervention Description
Macitentan 10 mg, oral tablet, to be taken once daily.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo oral tablet, to be taken once daily.
Primary Outcome Measure Information:
Title
Change From Baseline to Week 16 in Pulmonary Vascular Resistance (PVR) at Rest.
Description
The primary efficacy endpoint is defined as the PVR at rest at Week 16 expressed as percent of baseline PVR at rest.
Time Frame
From baseline to Week 16
Secondary Outcome Measure Information:
Title
Change From Baseline to Week 24 in Exercise Capacity, as Measured by the 6-minute Walk Distance (6MWD).
Description
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.
Time Frame
From baseline to Week 24
Title
Change From Baseline to Week 24 in Borg Dyspnea Index Collected at the End of the 6-minute Walk Test (6MWT).
Description
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.
Time Frame
From baseline to Week 24
Title
Proportion of Subjects With Worsening in WHO Functional Class (FC) From Baseline to Week 24
Description
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'.
Time Frame
From baseline to Week 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
84 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kelly Papadakis, MD
Organizational Affiliation
Actelion
Official's Role
Study Chair
Facility Information:
Facility Name
University Hospital Gasthuisberg / Interne Geneeskunde - I.G. Pneumologie
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Beijing Chao-Yang Hospital-Department of Respiration
City
Beijing
ZIP/Postal Code
100020
Country
China
Facility Name
Cardiovascular institute & Fuwai Hospital- Thrombus Center
City
Beijing
ZIP/Postal Code
100037
Country
China
Facility Name
The first affiliated hospital of guangzhou medical university-respiratory department
City
Guangzhou
ZIP/Postal Code
510120
Country
China
Facility Name
ngShanghai Pulmonary Hospital, Department of Pulmonary Circulation
City
Shanghai
ZIP/Postal Code
200433
Country
China
Facility Name
The General Hospital of Shenyang Military Region,Congenital Heart Disease Department
City
Shenyang
ZIP/Postal Code
110016
Country
China
Facility Name
Wuhan Asia Heart Hospital
City
Wuhan
ZIP/Postal Code
430022
Country
China
Facility Name
Centre for PPH, Charles University , II Interni klinika1.LF a VFN
City
Praha
ZIP/Postal Code
128 08
Country
Czechia
Facility Name
CHU de Bicêtre
City
Le Kremlin-Bicêtre cedex
ZIP/Postal Code
94275
Country
France
Facility Name
Hôpital Européen Georges Pompidou Service de Pneumologie, soins intensifs et endoscopies bronchiques
City
Paris cedex 15
ZIP/Postal Code
75908
Country
France
Facility Name
CHU de Toulouse Hopital Larrey
City
Toulouse Cedex 9
ZIP/Postal Code
31059
Country
France
Facility Name
Justus-Liebig-Universität Gießen
City
Giessen
ZIP/Postal Code
35392
Country
Germany
Facility Name
Thoraxklinik am Universitätsklinikum Heidelberg
City
Heidelberg
ZIP/Postal Code
69126
Country
Germany
Facility Name
Missionsärztliche Klinik gGmbH Akademisches Lehrkrankenhaus der Julius-Maximilians-Universität
City
Würzburg
ZIP/Postal Code
97074
Country
Germany
Facility Name
Semmelweis Egyetem
City
Budapest
ZIP/Postal Code
1125
Country
Hungary
Facility Name
Debreceni Egyetem Orvos- és Egészségtudományi Centrum, Kardiológiai Klinika
City
Debrecen
ZIP/Postal Code
4032
Country
Hungary
Facility Name
Severance Hospital, YonSei University Health System
City
Seoul
ZIP/Postal Code
3722
Country
Korea, Republic of
Facility Name
Lietuvos Sveikatos Mokslų Universiteto Ligoninės Kauno Klinikos Pulmonologijos-Imunologijos Klinika
City
Kaunas
ZIP/Postal Code
50161
Country
Lithuania
Facility Name
Instituto Nacional de Cardiologia (INC) Ignacio Chavez
City
Mexico City
ZIP/Postal Code
14080
Country
Mexico
Facility Name
Wojewódzki Szpital Specjalistyczny w Lublinie im. Stefana Kardynała Wyszyńskiego SPZOZ Oddział Kardiologii - Pododdział Intensywnego Nadzoru Kardiologicznego
City
Lublin
ZIP/Postal Code
20-718
Country
Poland
Facility Name
Wojewódzki Szpital Specjalistyczny we Wrocawiu
City
Wrocaw
ZIP/Postal Code
51-124
Country
Poland
Facility Name
Federal State Budgetary Institution "Scientific Research Institute of Systemic Problems of Cardiovascular Diseases", Siberian branch of RAMS
City
Kemerovo
ZIP/Postal Code
650002
Country
Russian Federation
Facility Name
Federal State Budgetary Institution "Russian Cardiology Scientific and Production Complex" of the Ministry of Health Care of the Russian Federation
City
Moscow
ZIP/Postal Code
121552
Country
Russian Federation
Facility Name
E.N.Meshalkin Novosibirsk State Research Institute Of Circulation Pathology Rosmedtechnology
City
Novosibirsk
ZIP/Postal Code
630055
Country
Russian Federation
Facility Name
Federal State Institution "Federal center of Heart, Blood and Endocrinology named after V.A.Almazov Rosmedtekhnologies"
City
St. Petersburg
ZIP/Postal Code
197341
Country
Russian Federation
Facility Name
Federal State Budgetary Institution "Research Institute for Cardiology" of Siberian Branch under the Russian Academy of Medical Sciences / Cardiovascular Surgery Department
City
Tomsk
ZIP/Postal Code
634012
Country
Russian Federation
Facility Name
University Hospital Zürich
City
Zürich
ZIP/Postal Code
8091
Country
Switzerland
Facility Name
King Chulalongkorn Memorial Hospital, Division of Respiratory and Respiratory Critical Care Medicine
City
Bangkok
ZIP/Postal Code
10330
Country
Thailand
Facility Name
Siriraj Hospital, Division of Respiratory Disease and Tuberculosis
City
Bangkok
ZIP/Postal Code
10700
Country
Thailand
Facility Name
MAHARAJ NAKORN CHIANG MAI HOSPITAL, Department of Internal Medicine
City
Chiang Mai
ZIP/Postal Code
50200
Country
Thailand
Facility Name
Istanbul University İstanbul Faculty Medicine Pulmonology Department
City
Capa_Istanbul
ZIP/Postal Code
34093
Country
Turkey
Facility Name
State Institute of Phthisiology and Pulmonology n.a. F.G. Yanovskiy of AMS Ukraine
City
Kyiv
ZIP/Postal Code
03680
Country
Ukraine
Facility Name
Lviv Regional Clinical Hospital, Cardiosurgery Department
City
Lviv
ZIP/Postal Code
79014
Country
Ukraine
Facility Name
Papworth Hospital NHS Trust, Pulmonary Vascular Diseases Unit
City
Cambridge
ZIP/Postal Code
CB23 3RE
Country
United Kingdom
Facility Name
Hammersmith Hospital
City
London
ZIP/Postal Code
W12 0HS
Country
United Kingdom
Facility Name
Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital, Pulmonary Vascular Medicine
City
Sheffield
ZIP/Postal Code
S10 2RX
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
28919201
Citation
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.
Results Reference
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Clinical Study to Assess the Efficacy, Safety and Tolerability of Macitentan in Subjects With Inoperable Chronic Thromboembolic Pulmonary Hypertension
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