Clinical trial NCT02021292: Clinical Study to Assess the Efficacy, Safety and Tolerability of Macitentan in Subjects With Inoperable Chronic Thromboembolic Pulmonary Hypertension
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Thromboembolic Pulmonary Hypertension
Keywords: Chronic thromboembolic pulmonary hypertension (CTEPH)
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2013-12-27
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 84
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: Change From Baseline to Week 16 in Pulmonary Vascular Resistance (PVR) at Rest.
timeFrame: From baseline to Week 16
Secondary outcomes:
measure: Change From Baseline to Week 24 in Exercise Capacity, as Measured by the 6-minute Walk Distance (6MWD).
timeFrame: From baseline to Week 24
measure: Change From Baseline to Week 24 in Borg Dyspnea Index Collected at the End of the 6-minute Walk Test (6MWT).
timeFrame: From baseline to Week 24
measure: Proportion of Subjects With Worsening in WHO Functional Class (FC) From Baseline to Week 24
timeFrame: From baseline to Week 24
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: University Hospital Gasthuisberg / Interne Geneeskunde - I.G. Pneumologie
city: Beijing
country: China
facility: Beijing Chao-Yang Hospital-Department of Respiration
city: Beijing
country: China
facility: Cardiovascular institute & Fuwai Hospital- Thrombus Center
city: Guangzhou
country: China
facility: The first affiliated hospital of guangzhou medical university-respiratory department
city: Shanghai
country: China
facility: ngShanghai Pulmonary Hospital, Department of Pulmonary Circulation
city: Shenyang
country: China
facility: The General Hospital of Shenyang Military Region,Congenital Heart Disease Department
city: Wuhan
country: China
facility: Wuhan Asia Heart Hospital
city: Praha
country: Czechia
facility: Centre for PPH, Charles University , II Interni klinika1.LF a VFN
city: Le Kremlin-Bicêtre cedex
country: France
facility: CHU de Bicêtre
city: Paris cedex 15
country: France
facility: Hôpital Européen Georges Pompidou Service de Pneumologie, soins intensifs et endoscopies bronchiques
city: Toulouse Cedex 9
country: France
facility: CHU de Toulouse Hopital Larrey
city: Giessen
country: Germany
facility: Justus-Liebig-Universität Gießen
city: Heidelberg
country: Germany
facility: Thoraxklinik am Universitätsklinikum Heidelberg
city: Würzburg
country: Germany
facility: Missionsärztliche Klinik gGmbH Akademisches Lehrkrankenhaus der Julius-Maximilians-Universität
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Orvos- és Egészségtudományi Centrum, Kardiológiai Klinika
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, YonSei University Health System
city: Kaunas
country: Lithuania
facility: Lietuvos Sveikatos Mokslų Universiteto Ligoninės Kauno Klinikos Pulmonologijos-Imunologijos Klinika
city: Mexico City
country: Mexico
facility: Instituto Nacional de Cardiologia (INC) Ignacio Chavez
city: Lublin
country: Poland
facility: Wojewódzki Szpital Specjalistyczny w Lublinie im. Stefana Kardynała Wyszyńskiego SPZOZ Oddział Kardiologii - Pododdział Intensywnego Nadzoru Kardiologicznego
city: Wrocaw
country: Poland
facility: Wojewódzki Szpital Specjalistyczny we Wrocawiu
city: Kemerovo
country: Russian Federation
facility: Federal State Budgetary Institution "Scientific Research Institute of Systemic Problems of Cardiovascular Diseases", Siberian branch of RAMS
city: Moscow
country: Russian Federation
facility: Federal State Budgetary Institution "Russian Cardiology Scientific and Production Complex" of the Ministry of Health Care of the Russian Federation
city: Novosibirsk
country: Russian Federation
facility: E.N.Meshalkin Novosibirsk State Research Institute Of Circulation Pathology Rosmedtechnology
city: St. Petersburg
country: Russian Federation
facility: Federal State Institution "Federal center of Heart, Blood and Endocrinology named after V.A.Almazov Rosmedtekhnologies"
city: Tomsk
country: Russian Federation
facility: Federal State Budgetary Institution "Research Institute for Cardiology" of Siberian Branch under the Russian Academy of Medical Sciences / Cardiovascular Surgery Department
city: Zürich
country: Switzerland
facility: University Hospital Zürich
city: Bangkok
country: Thailand
facility: King Chulalongkorn Memorial Hospital, Division of Respiratory and Respiratory Critical Care Medicine
city: Bangkok
country: Thailand
facility: Siriraj Hospital, Division of Respiratory Disease and Tuberculosis
city: Chiang Mai
country: Thailand
facility: MAHARAJ NAKORN CHIANG MAI HOSPITAL, Department of Internal Medicine
city: Capa_Istanbul
country: Turkey
facility: Istanbul University İstanbul Faculty Medicine Pulmonology Department
city: Kyiv
country: Ukraine
facility: State Institute of Phthisiology and Pulmonology n.a. F.G. Yanovskiy of AMS Ukraine
city: Lviv
country: Ukraine
facility: Lviv Regional Clinical Hospital, Cardiosurgery Department
city: Cambridge
country: United Kingdom
facility: Papworth Hospital NHS Trust, Pulmonary Vascular Diseases Unit
city: London
country: United Kingdom
facility: Hammersmith Hospital
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital, Pulmonary Vascular Medicine
Study officials:
affiliation: Actelion
name: Kelly Papadakis, MD
role: STUDY_CHAIR
References:
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.