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

Chronic Thromboembolic Pulmonary Hypertension Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02021292
• Other study ID #: AC-055E201
• Status: Completed
• Phase: Phase 2
• Start date: August 20, 2014
• Est. completion date: September 28, 2016

Study information

• Verified date: May 2020
• Source: Actelion
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: September 28, 2016
• Est. primary completion date: September 28, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 84 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Thromboembolic Pulmonary Hypertension
• Hypertension
• Hypertension, Pulmonary

Intervention

Drug:
• Macitentan
Macitentan 10 mg, oral tablet, to be taken once daily.
• Placebo
Matching placebo oral tablet, to be taken once daily.

Locations

Country	Name	City	State
Belgium	University Hospital Gasthuisberg / Interne Geneeskunde - I.G. Pneumologie	Leuven
China	Beijing Chao-Yang Hospital-Department of Respiration	Beijing
China	Cardiovascular institute & Fuwai Hospital- Thrombus Center	Beijing
China	The first affiliated hospital of guangzhou medical university-respiratory department	Guangzhou
China	ngShanghai Pulmonary Hospital, Department of Pulmonary Circulation	Shanghai
China	The General Hospital of Shenyang Military Region,Congenital Heart Disease Department	Shenyang
China	Wuhan Asia Heart Hospital	Wuhan
Czechia	Centre for PPH, Charles University , II Interni klinika1.LF a VFN	Praha
France	CHU de Bicêtre	Le Kremlin-Bicêtre cedex
France	Hôpital Européen Georges Pompidou Service de Pneumologie, soins intensifs et endoscopies bronchiques	Paris cedex 15
France	CHU de Toulouse Hopital Larrey	Toulouse Cedex 9
Germany	Justus-Liebig-Universität Gießen	Giessen
Germany	Thoraxklinik am Universitätsklinikum Heidelberg	Heidelberg
Germany	Missionsärztliche Klinik gGmbH Akademisches Lehrkrankenhaus der Julius-Maximilians-Universität	Würzburg
Hungary	Semmelweis Egyetem	Budapest
Hungary	Debreceni Egyetem Orvos- és Egészségtudományi Centrum, Kardiológiai Klinika	Debrecen
Korea, Republic of	Severance Hospital, YonSei University Health System	Seoul
Lithuania	Lietuvos Sveikatos Mokslu Universiteto Ligonines Kauno Klinikos Pulmonologijos-Imunologijos Klinika	Kaunas
Mexico	Instituto Nacional de Cardiologia (INC) Ignacio Chavez	Mexico City
Poland	Wojewódzki Szpital Specjalistyczny w Lublinie im. Stefana Kardynala Wyszynskiego SPZOZ Oddzial Kardiologii - Pododdzial Intensywnego Nadzoru Kardiologicznego	Lublin
Poland	Wojewódzki Szpital Specjalistyczny we Wrocawiu	Wrocaw
Russian Federation	Federal State Budgetary Institution "Scientific Research Institute of Systemic Problems of Cardiovascular Diseases", Siberian branch of RAMS	Kemerovo
Russian Federation	Federal State Budgetary Institution "Russian Cardiology Scientific and Production Complex" of the Ministry of Health Care of the Russian Federation	Moscow
Russian Federation	E.N.Meshalkin Novosibirsk State Research Institute Of Circulation Pathology Rosmedtechnology	Novosibirsk
Russian Federation	Federal State Institution "Federal center of Heart, Blood and Endocrinology named after V.A.Almazov Rosmedtekhnologies"	St. Petersburg
Russian Federation	Federal State Budgetary Institution "Research Institute for Cardiology" of Siberian Branch under the Russian Academy of Medical Sciences / Cardiovascular Surgery Department	Tomsk
Switzerland	University Hospital Zürich	Zürich
Thailand	King Chulalongkorn Memorial Hospital, Division of Respiratory and Respiratory Critical Care Medicine	Bangkok
Thailand	Siriraj Hospital, Division of Respiratory Disease and Tuberculosis	Bangkok
Thailand	MAHARAJ NAKORN CHIANG MAI HOSPITAL, Department of Internal Medicine	Chiang Mai
Turkey	Istanbul University Istanbul Faculty Medicine Pulmonology Department	Capa_Istanbul
Ukraine	State Institute of Phthisiology and Pulmonology n.a. F.G. Yanovskiy of AMS Ukraine	Kyiv
Ukraine	Lviv Regional Clinical Hospital, Cardiosurgery Department	Lviv
United Kingdom	Papworth Hospital NHS Trust, Pulmonary Vascular Diseases Unit	Cambridge
United Kingdom	Hammersmith Hospital	London
United Kingdom	Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital, Pulmonary Vascular Medicine	Sheffield

Sponsors (1)

Lead Sponsor	Collaborator
Actelion

Countries where clinical trial is conducted

Belgium,  China,  Czechia,  France,  Germany,  Hungary,  Korea, Republic of,  Lithuania,  Mexico,  Poland,  Russian Federation,  Switzerland,  Thailand,  Turkey,  Ukraine,  United Kingdom, 

References & Publications (1)

Ghofrani HA, Simonneau G, D'Armini AM, Fedullo P, Howard LS, Jaïs 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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