Clinical Study to Evaluate the Effects of Macitentan on Exercise Capacity in Subjects With Eisenmenger Syndrome (MAESTRO)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2016 by Actelion
Information provided by (Responsible Party):
Actelion Identifier:
First received: November 29, 2012
Last updated: July 21, 2016
Last verified: July 2016
Clinical study to assess the efficacy, safety, and tolerability of macitentan in subjects with Eisenmenger Syndrome.

Condition Intervention Phase
Pulmonary Arterial Hypertension
Drug: Macitentan 10 mg
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multi-center, Double-blind, Randomized, Placebo-controlled, Parallel-group, Phase 3 Study to Evaluate the Effects of Macitentan on Exercise Capacity in Subjects With Eisenmenger Syndrome

Resource links provided by NLM:

Further study details as provided by Actelion:

Primary Outcome Measures:
  • Change from baseline to Week 16 in exercise capacity, as measured by 6MWD [ Time Frame: From baseline to Week 16 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from baseline to Week 16 in WHO functional class [ Time Frame: From baseline to Week 16 ] [ Designated as safety issue: No ]
  • Change from baseline to Week 16 in dyspnea (assessed by the Borg dyspnea index) [ Time Frame: From baseline to Week 16 ] [ Designated as safety issue: No ]
  • Change from baseline to Week 16 in quality of life (assessed by the SF-36 questionnaire) [ Time Frame: From baseline to Week 16 ] [ Designated as safety issue: No ]

Estimated Enrollment: 220
Study Start Date: May 2013
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Macitentan
Subjects receive macitentan 10 mg oral tablet once daily
Drug: Macitentan 10 mg
Macitentan 10 mg oral tablet once daily
Other Name: ACT-064992
Placebo Comparator: Placebo
Subjects receive macitentan-matching placebo oral tablet once daily
Drug: Placebo
Macitentan-matching placebo oral tablet once daily


Ages Eligible for Study:   12 Years and older   (Child, Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Subjects:

    • not participating in the hemodynamic sub-study: males or females ≥ 12 years of age.
    • participating in the hemodynamic sub-study: males or females ≥ 18 years of age.
  • Subjects (including those with Down Syndrome [DS]) with confirmed Eisenmenger Syndrome [ES] (European Society of Cardiology [ESC] and the European Respiratory Society [ERS] guidelines):

    1. Established by echocardiography as:

      • Large congenital shunting defect at atrial, ventricular or arterial level*
      • and right to left shunt or bi-directional shunt with prevalent right to left direction.
    2. Resting peripheral oxygen saturation (SpO2) ≤ 90% and > 70% (pulse oximetry, room air).

The lower limit is 65% if a subject is living at an altitude greater than 2500 m above sea level.

*Subjects with any of the following open defects are eligible for the study either as an isolated defect or in combination:

  • atrial septal defect (ASD)
  • ventricular septal defect (VSD)
  • partial or complete atrioventricular septal defect (AVSD)
  • patent ductus arteriosus (PDA)
  • aortopulmonary window (AP window)
  • total or partial anomalous pulmonary venous return (TAPVR, PAPVR) The defects may be either unoperated or previously palliated surgically (provided significant residual defect remains).

The Steering Committee will review the echocardiography data of all subjects (main study and sub study) to confirm eligibility prior to Randomization.

  • Subjects with the following findings at cardiac catheterization:

    • Mean resting pulmonary arterial pressure (mPAP) > 25 mmHg
    • Pulmonary capillary wedge pressure (PCWP) or mean left atrial pressure (LAP) or left ventricular end diastolic pressure (LVED) ≤ 15 mmHg
    • Pulmonary vascular resistance (PVR) ≥ 800 dyn∙s/cm5 or ≥ 10 Wood units
  • Subjects with WHO functional class ≥ II.
  • Subjects able to reliably perform the the 6-minute walk test (6MWT) with a minimum distance of 50 m and a maximum distance of 450 m.

Exclusion Criteria:

- Main study and hemodynamic sub-study: Any of the following conditions previously known or identified via cardiac catheterization or echocardiography:

  • Pulmonary arterial or venous stenosis > 25% size of native pulmonary artery (PA) or pulmonary vein
  • Severe tricuspid regurgitation in the setting of left to right shunt at the ventricular or atrial level
  • Greater than mild tricuspid stenosis
  • Intracavitary RV outflow obstruction
  • Greater than mild mitral stenosis
  • Intracavitary LV outflow obstruction
  • Subvalvular or supravalvular aortic stenosis
  • Aortic coarctation
  • Greater than moderate mitral regurgitation
  • Recognized extracardiac systemic venous collaterals to the pulmonary venous circulation
  • Recognized hepatic wedge pressure-inferior vena cava pressure gradient >12 mm Hg
  • PCWP "v" waves >20 mmHg
  • Tetralogy of Fallot
  • Truncus arteriosus
  • Interrupted aortic arch
  • Transposition of great arteries
  • Single ventricle defects: absent AV connection (mitral or tricuspid atresia), double inlet AV connections left or right ventricle, functional univentricular heart (unbalanced AVSD, hypoplastic RV, double outlet RV), hypoplastic left heart syndrome
  • Ebstein's anomaly
  • Severe aortic regurgitation
  • Pulmonary atresia
  • PAPVR or TAPVR, ONLY if there is lung hypoplasia or if documentation confirming the absence of lung hypoplasia does not exist.

For subjects participating in the hemodynamic sub-study the following will also be considered exclusion criteria:

  • SVC stenosis >25% size of native vessel
  • PDA, AP window, TAPVR, PAPVR, or ASD sinus venosus with anomalous pulmonary veins
  • Down Syndrome

    • Subjects with deterioration of their clinical status within 3 months prior to Screening or during the Screening period.
    • Known moderate-to-severe restrictive (i.e., total lung capacity [TLC] < 60% of predicted value) or obstructive lung disease (i.e., forced expiratory volume in one second [FEV1] < 80 % of predicted value, and with FEV1 / forced vital capacity [FVC] < 70%)
    • Treatment with prostanoids within 1 month prior to Randomization
    • Subjects who initiated a PDE-5 inhibitor within 1 month prior to Randomization or those on a PDE-5 inhibitor for whom the dose has not been stable within 1 month prior to Randomization
    • Treatment with endothelin receptor antagonists (ERAs) within 1 month prior to Randomization
    • Subjects who initiated diuretics within 1 week prior to Randomization or subjects whose diuretic treatment has not been stable for at least 1 week prior to Randomization
    • Subjects being considered for an organ transplant
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01743001

Contact: CTD Clinical Trial Disclosure Desk

  Hide Study Locations
United States, California
Ahmanson/UCLA Heart Disease Center Recruiting
Los Angeles, California, United States, 90095
Contact: Jamil Aboulhosn    310-291-2058   
Stanford Hospital and Clinic Recruiting
Palo Alto, California, United States, 94304
Contact: Anitra W. Romfh         
Liu Ctr For Pulm Hypertension Terminated
Torrance, California, United States, 90502-2006
United States, Colorado
University of Colorado Anschutz Medical Campus Withdrawn
Aurora, Colorado, United States, 80045
United States, Georgia
Emory University Hospital/the Emory Clinic Recruiting
Atlanta, Georgia, United States, 30322
Contact: Wendy Book    404-778-5545   
United States, Maryland
Univ of Maryland (Baltimore) Terminated
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Children'S Hosp Boston (Chb), Paed Cardio Terminated
Boston, Massachusetts, United States, 02115
United States, Missouri
Barnes-Jewish Hosp/Wash Univ School of Med Recruiting
St. Louis, Missouri, United States, 63110
Contact: Ari Cedars    314-362-3794   
United States, Nevada
Children'S Heart Center Nevada Recruiting
Las Vegas, Nevada, United States, 89109
Contact: Abraham Rothman    702-732-1290   
United States, New York
Columbia Univ Med Ctr - Children'S Hosp of Ny Presbyterian Withdrawn
New York, New York, United States, 10032
United States, Ohio
Cleveland Clinic Withdrawn
Cleveland, Ohio, United States, 44195
Nationwide Children's Hospital Recruiting
Columbus, Ohio, United States, 43210
Contact: Curt Daniels    614-293-4967   
United States, Texas
Texas Children'S Hosp - Dept of Cardiology Recruiting
Houston, Texas, United States, 77030-2303
Contact: Wayne J. Franklin    832-826-5600   
Gen Hosp Univ Vienna Dept Cardiology Recruiting
Vienna, Austria, A-1090
Contact: Irene Lang    + 43 1 40 400 49 65   
Ulb Erasme, Cardiology Withdrawn
Brussels, Belgium, 1070
University Hospital Gasthuisberg - Pneumologie Terminated
Leuven, Belgium, 3000
Mhat Nat Card Hosp - Cardiology Clinic Recruiting
Sofia, Bulgaria, 1309
Contact: Borislav Georgiev    +359 888 370109   
Mhat Nat Card Hosp - Pediatric Clin / Ped Card Dept Recruiting
Sofia, Bulgaria, 1309
Contact: Margarita Tzonzarova    +359 2 8221804   
Mhat Sveta Anna Clin Card Recruiting
Sofia, Bulgaria, 1750
Contact: Vasil Velchev    +359 899973015   
Mhat Steva Marina Clin Card Withdrawn
Varna, Bulgaria, 9010
Canada, Alberta
Univ of Alberta Hospital - 2E4.33 Terminated
Edmonton, Alberta, Canada, T6G 2B7
Canada, British Columbia
Hosp University of British Columbia - St. Paul'S Hospital Withdrawn
Vancouver, British Columbia, Canada, V6Z 1Y6
Inst Nat Torax, Unidad Cardiopatia Congenitas Del Adulto Recruiting
Providencia, Chile
Contact: Polentzi Uriarte    +56 2 25755008   
Clinica Tabancura - Cardio Unit Recruiting
Santiago, Chile, 7650018
Contact: Pablo Sepulveda Varela    562-3954364   
China, Guangdong
Guangdong General Hospital, Cardiology Dpt Active, not recruiting
Guangzhou, Guangdong, China, 510080
China, Hubei
Wu Han Asia Heart Hosp Active, not recruiting
Wuhan, Hubei, China, 430022
China, Liaoning
The General Hosp of Shenyang Military Region Active, not recruiting
Shenyang, Liaoning, China, 110016
Beijing Anzhen Hospital, Cardiology Dpt Active, not recruiting
Beijing, China, 100029
Cardiovascular Institute&Fuwai Hospital Active, not recruiting
Beijing, China, 100037
Shanghai Pulmonary Hospital, Dept of Pulmonary Circulation Active, not recruiting
Shanghai, China, 200433
Czech Republic
Fn Brno Bohunice Cardiology Terminated
Brno, Czech Republic, 625 00
Gen Faculty Hosp Prague Cardiology Clin Completed
Praha 2, Czech Republic, 128 08
Hosp Na Homolce, Cardiology Dept. Terminated
Praha 5, Czech Republic, 150 30
Hosp La Timone - Dept Pediatric Cardiology Recruiting
Marseille Cedex 5, France, 13385
Contact: Alain Fraisse    +33 4 91 38 67 50   
Hosp Laennec - Dept Cardiology Recruiting
Nantes Cedex 1, France, 44093
Contact: Patrice Guérin    +33 2 40 16 55 89   
Hosp Pompidou - Dept Congenital Cardiac Diseases Recruiting
Paris Cedex 15, France, 75908
Contact: Laurence Iserin         
Hosp Cardiology Haut Leveque - Dept Congenital Diseases Recruiting
Pessac, France, 33604
Contact: Jean-Benoit Thambo    +33 5 57 65 64 65   
Herzzentrum Berlin, Ped Cardiology Recruiting
Berlin, Germany, 13353
Contact: Oliver Miera    +49 (0) 30 4593 2800   
Universitätsklinikum Giessen - Pediatric Heart Center Recruiting
Giessen, Germany, 35392
Contact: Christian Apitz    +49 (0) 6419943427/ 99434277   
Uni Heidelberg - Kinderkardiologie Recruiting
Heidelberg, Germany, D-69120
Contact: Matthias Gorenflo    +49(0)6221/56-4605   
Uni Münster (Ukm) - Emah Recruiting
Muenster, Germany, 48149
Contact: Gerhard-Paul Diller   
Deutsches Herzzentrum München Kinderkardiologie Withdrawn
München, Germany, 80636
Onasseio Cardiosurgical Hospital Recruiting
Athens, Greece, 17674
Contact: Spyridon Rammos         
Ahepa University General Hospital Recruiting
Thessaloniki, Greece, 54636
Contact: Haralampos Karvounis         
Gottsegen Gyorgy National Card Inst - Adult Cardiology Terminated
Budapest, Hungary, 1096
Univ of Szeged Clin Ctr - Ii Dept of Int Med and Cardio Ctr Terminated
Szeged, Hungary, 6720
Carmel Med Ctr - Pulm Unit Withdrawn
Haifa, Israel, 34362
Rabin Medical Centre - Pulmonology Recruiting
Petach Tikvah, Israel, 49100
Contact: Mordechai Kramer    +972-3-937-7221   
Hosp Sant'Orsola Malpighi - Dept Cardiology Recruiting
Bologna, Italy, 40138
Contact: Nazzareno Galiè    +39 051 6363434;   
Hosp San Matteo - Dept Cardiology Withdrawn
Pavia, Italy, 27100
Institut Jantung Negara Active, not recruiting
Kuala Lumpur, Malaysia, 50400
Unidad de Investigacion Clin En Med, Sc (Udicem) Recruiting
Monterrey, Nuevo Leon, Mexico, 64718
Contact: Carlos Jerjes Sanchez    52-81-81-43-07-83   
Hospital Infantil de Mexico Federico Gomez Withdrawn
Mexico City, Mexico, 06720
Instituto Nacional de Cardiologia (Inc) Ignacio Chavez Recruiting
Mexico City, Mexico, 14080
Contact: Tomas Rene Pulido Zamudio    52-55-5573-2911 Ext. 1355   
Hospital General de Puebla Withdrawn
Puebla, Mexico
Instituto de Corazon de Querètaro Recruiting
Querétaro, Mexico
Contact: Marco Alcocer    (442) 216-2745   
Umc Groningen Ped Cardiology Completed
Groningen, Netherlands, 9713 GZ
PHC, MAB Active, not recruiting
Manila, Philippines
Cardiology Gdańsk Univ Recruiting
Gdańsk, Poland, 80-952
Contact: Grzegorz Raczak    +48 58 349 39 10   
Cardiology Katowice Univ Withdrawn
Katowice, Poland, 40-635
Cardiology Kraków Univ Recruiting
Krakow, Poland, 31-202
Contact: Piotr Podolec    +48 12 614 33 99   
Cardiology Poznań Univ Recruiting
Poznań, Poland, 61-848
Contact: Tatiana Mularek-Kubzdela    +48 61 854 9146   
Cardiology (Chd) Warszawa Univ Recruiting
Warszawa, Poland, 04-628
Contact: Piotr Hoffman    +48 22 343 44 00   
Cardiology Wrocław Recruiting
Wrocław, Poland, 51-124
Contact: Jerzy Lewczuk    +48 71 32 70 530   
Cardiology Zabrze Univ 2 Recruiting
Zabrze, Poland, 41-800
Contact: Mariusz Gasior    +48 32 37 33 860   
Hosp Univ Coimbra - Dpt Cardiology Recruiting
Coimbra, Portugal, 3000-075
Contact: Graça Castro    +351 934 207 058   
Hosp Sta Marta - Dept Cardiology Recruiting
Lisboa, Portugal, 1169-024
Contact: Ana María Figueiredo Agapito    +351 965 139 032   
Er Inst For Cardvasc Dis "Prof Dr Cc Iliescu" - Card Ii Recruiting
Bucuresti, Romania, 022328
Contact: Ioan Mircea Coman    +40 21 302 1110   
Cardio Med Srl Recruiting
Targu-Mures, Romania, 540136
Contact: Theodora Benedek    +40 265 217 333   
Clin Hosp For Inf and Pulm Dis Victor Babes - Ii Pulm Recruiting
Timisoara, Romania, 300312
Contact: Nicoleta Sorina Bertici    +40 256 20 76 70      
Russian Federation
Sci Institute Systemic Problems Cardio Diseases Kemerovo Recruiting
Kemerovo, Russian Federation, 650002
Contact: Olga Barbarash    +7 3842 521474   
Russian Cardiology Scientific and Production Complex Recruiting
Moscow, Russian Federation, 121552
Contact: Tamila Martynyuk    +7 4954 146 450   
V. A. Almazov Institute of Cardiology Recruiting
St Petersburg, Russian Federation, 197341
Contact: Olga M Moiseeva    + 78125528114 or + 79213068249   
Cardiology Scientific Research Institute Withdrawn
Tomsk, Russian Federation, 634012
Dedinje Cardiovasc Inst - Cardiovasc Research Ctr Recruiting
Belgrade, Serbia, 11040
Contact: Petar Otašević    +381 11 3601 669   
Mother and Child Health Care Inst "Dr Vukan Cupic" Recruiting
Belgrade, Serbia, 11070
Contact: Jovan Kosutic    +381 11 3108 108   
Clin Hosp Ctr Zemun - Cardiology Dept Recruiting
Belgrade, Serbia, 11080
Contact: Biljana Putniković    +381 11 3772 761   
South Africa
Ufs Paediatric Cardiology Withdrawn
Bloemfontein, South Africa, 9300
Tread Research Withdrawn
Cape Town, South Africa, 7505
Chris Hani Baragwanath -Soweto Cardiovascular Withdrawn
Johannesburg, South Africa, 2013
Hosp Univ Puerta Hierro - Dpt Cardiology Recruiting
Majadahonda, Madrid, Spain, 28222
Contact: Javier Segovia Cubero         
Hosp Univ Vall D'Hebron - Dpt Congenital Heart Disease Adult Recruiting
Barcelona, Spain, 08035
Contact: Laura Dos Subira    +34934893000 / +34932746000   
Hosp Univ Gregorio Marañon Dpt Cardiology Withdrawn
Madrid, Spain, 28007
Hospital 12 Octubre Recruiting
Madrid, Spain, 28041
Contact: Pilar Escribano    34913908669   
Hosp Univ Virgen Macarena - Dpt Cardiology Recruiting
Sevilla, Spain, 41007
Contact: Pastora Gallego    +34 955 00 80 00   
Hosp Universitario La Fe Dpt Cardiology Recruiting
Valencia, Spain, 46009
Contact: Joaquín Rueda    +34 963 862 700   
Kaohsiung Veterans Gen Hosp / Intensive Care Unit Withdrawn
Kaohsiung, Taiwan, 813
Taichung, Taiwan, 40705
National Taiwan Univ Hosp-Dept of Paed Withdrawn
Taipei, Taiwan, 100
Hacettepe Unv. Dept. of Pediatry Recruiting
Ankara, Turkey, 06100
Contact: DURSUN ALEHAN    +90312 305 1157   
Gazi University Recruiting
Ankara, Turkey, 06500
Contact: Sedef Tunaoglu    90312 202 6129      
Kardiyoloji Enstitisü Recruiting
Istanbul, Turkey, 34096
Contact: Serdar Kucukoglu    0090-212-4592033   
Kosuyolu Kardiyoloji Recruiting
Kartal-Istanbul, Turkey, 34865
Contact: Cihangir Kaymaz    +90 216 549 4041   
Omu Pediatry Recruiting
Samsun, Turkey, 55139
Contact: Kemal Baysal    90 362 3121919      
United Kingdom
Bristol Univ Hosp Congenital Heart Centre Recruiting
Bristol, United Kingdom, BS2 8BJ
Contact: Robert M R Tulloh    +44 117 342 8176   
The Brompton- Heart Centre and Centre For Pulmonary Hyperten Withdrawn
London, United Kingdom, SW3 6NP
Manchester Royal Infirmary - Manchester Heart Centre Terminated
Manchester, United Kingdom, M13 9WL
Hanoi Medical University Hospital Completed
Hanoi, Vietnam
Children's Hospital, Ho Chi Minh Active, not recruiting
Ho Chi Minh, Vietnam
Tam Duc Hospital Active, not recruiting
Ho Chi Minh, Vietnam
Sponsors and Collaborators
  More Information

Responsible Party: Actelion Identifier: NCT01743001     History of Changes
Other Study ID Numbers: AC-055-305 
Study First Received: November 29, 2012
Last Updated: July 21, 2016
Health Authority: China: Food and Drug Administration
United States: Food and Drug Administration
Chile: Instituto de Salud Pública de Chile
Vietnam: Ministry of Health
Russia: Ministry of Health of the Russian Federation
Germany: Federal Institute for Drugs and Medical Devices
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Malaysia: Ministry of Health
Philippines: Department of Health
South Africa: Medicines Control Council
Hungary: National Institute of Pharmacy
Austria: Austrian Medicines and Medical Devices Agency
Serbia and Montenegro: Agency for Drugs and Medicinal Devices
Mexico: Federal Commission for Protection Against Health Risks
Israel: Ministry of Health
Belgium: Federal Agency for Medicinal Products and Health Products
Italy: The Italian Medicines Agency
Bulgaria: Bulgarian Drug Agency
Taiwan: Department of Health
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Portugal: National Pharmacy and Medicines Institute
Philippines : Food and Drug Administration
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
United Kingdom: Medicines and Healthcare Products Regulatory Agency
India: Drugs Controller General of India
Canada: Health Canada
Turkey: Ministry of Health

Keywords provided by Actelion:
exercise capacity
Eisenmenger Syndrome

Additional relevant MeSH terms:
Familial Primary Pulmonary Hypertension
Eisenmenger Complex
Pathologic Processes
Vascular Diseases
Cardiovascular Diseases
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases
Heart Defects, Congenital
Cardiovascular Abnormalities
Heart Diseases
Congenital Abnormalities
Endothelin A Receptor Antagonists
Endothelin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Endothelin B Receptor Antagonists processed this record on August 24, 2016