MAESTRO (Macitentan in Eisenmenger Syndrome To Restore Exercise Capacity)

This study is currently recruiting participants.
Verified April 2014 by Actelion
Information provided by (Responsible Party):
Actelion Identifier:
First received: November 29, 2012
Last updated: April 14, 2014
Last verified: April 2014

Clinical study to assess the efficacy, safety, and tolerability of macitentan in subjects with Eisenmenger Syndrome.

Condition Intervention Phase
Eisenmenger Syndrome
Drug: Macitentan 10 mg, oral tablet, to be taken once daily.
Drug: Matching placebo oral tablet, to be taken once daily.
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
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: Baseline to Week 16 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from baseline to Week 16 in WHO functional class [ Time Frame: 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: 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: Baseline to Week 16 ] [ Designated as safety issue: No ]

Estimated Enrollment: 220
Study Start Date: May 2013
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Macitentan
Macitentan 10 mg, oral tablet, to be taken once daily.
Drug: Macitentan 10 mg, oral tablet, to be taken once daily.
Macitentan 10 mg, oral tablet, to be taken once daily.
Other Name: Macitentan, ACT-064992
Placebo Comparator: Placebo
Matching placebo oral tablet, to be taken once daily.
Drug: Matching placebo oral tablet, to be taken once daily.
Matching placebo oral tablet, to be taken once daily.
Other Name: Placebo


Ages Eligible for Study:   12 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Subjects:

    • not participating in the hemodynamic sub-study: males or females ≥ 12 and ≤ 70 years of age.
    • participating in the hemodynamic sub-study: males or females ≥ 18 and ≤ 70 years of age.
  • Subjects with confirmed ES (European Society of Cardiology [ESC] and the European Respiratory Society [ERS] guidelines):

    • Established by echocardiography as:

      • Isolated ASD > 2 cm in diameter,
      • or isolated VSD > 1 cm in diameter,
      • or presence of both ASD and VSD (with either VSD ≤ 1 cm in diameter and ASD > 2 cm in diameter, or VSD > 1 cm in diameter and ASD ≤ 2 cm in diameter, or VSD > 1 cm in diameter and ASD > 2 cm in diameter),
      • and right to left shunt or bi-directional shunt with prevalent right to left direction.
    • Unoperated, or previously palliated surgically for defects mentioned above (incomplete closure) and including fully repaired patent ductus arteriosus (PDA).
    • Resting peripheral arterial oxygen saturation (SaO2) ≤ 90% and >70% (pulse oximetry, room air).
  • Cardiac catheterization measurements must show the following:

    • mPAP > 25 mmHg,
    • PCWP or LAP or LVED ≤ 15 mmHg,
    • PVR ≥ 800 dyn∙s/cm5 or ≥ 10 Wood units.
  • Subjects with WHO functional class ≥ II.
  • Subjects able to perform the 6MWT with a minimum distance of 50 m and a maximum distance of 450 m.

Exclusion Criteria:

  • PAH not fulfilling the criteria of ES as described in inclusion criteria (e.g., complex cardiac defects, single ventricle, and unrepaired or partially repaired PDA).
  • Known moderate-to-severe restrictive (i.e., TLC < 60% of predicted value) or obstructive lung disease (i.e., FEV1 < 80 % of predicted, with FEV1 / FVC < 70%).
  • Down Syndrome.
  • Treatment with PDE-5 inhibitors or prostanoids within 1 month prior to Randomization.
  • Treatment with 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 within 1 week prior to Randomization.
  • Subjects being considered for an organ transplant.
  Contacts and Locations
Please refer to this study by its identifier: NCT01743001

  Hide Study Locations
United States, California
Cedars Sinai Heart Institute Not yet recruiting
Beverly Hills, California, United States, 90211
Contact: Antoine Hage    310-248-8300   
Ucsd Dept. of Pulm/Critical Care Not yet recruiting
La Jolla, California, United States, 92093-0052
Contact: Hyong (Nick) Kim    619-543-7300   
Ahmanson/UCLA Heart Disease Center Recruiting
Los Angeles, California, United States, 90095
Contact: Jamil Aboulhosn    310-291-2058   
Liu Ctr For Pulm Hypertension Recruiting
Torrance, California, United States, 90502-2006
Contact: Ronald Oudiz    310-222-2515   
United States, Colorado
University of Colorado Anschutz Medical Campus Recruiting
Aurora, Colorado, United States, 80045
Contact: Joseph Kay    720-848-6585   
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) Recruiting
Baltimore, Maryland, United States, 21201
Contact: Stacy Fisher   
United States, Massachusetts
Children'S Hosp Boston (Chb), Paed Cardio Recruiting
Boston, Massachusetts, United States, 02115
Contact: Alexander Opotowsky    617-355-6508   
Massachusetts General Hospital Heart Center Not yet recruiting
Boston, Massachusetts, United States, 02114
Contact: Ami Bhatt    617-726-8510   
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 Recruiting
New York, New York, United States, 10032
Contact: Erika Rosenzweig    212-305-4436   
United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Contact: Richard Krasuski    216-445-7430   
Ohio State Univ Medical Center 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 Recruiting
Brussels, Belgium, 1070
Contact: Jean-Luc Vachiéry    +32-2-555 39 14   
University Hospital Gasthuisberg - Pneumologie Recruiting
Leuven, Belgium, 3000
Contact: Marion Delcroix    +32 16 34 68 33   
Mhat Nat Card Hosp - Pediatric Clin / Ped Card Dept Recruiting
Sofia, Bulgaria, 1309
Contact: Margarita Tzonzarova    +359 2 8221804   
Mhat Nat Card Hosp - Cardiology Clinic Recruiting
Sofia, Bulgaria, 1309
Contact: Borislav Georgiev    +359 888 370109   
Mhat Sveta Anna Clin Card Recruiting
Sofia, Bulgaria, 1750
Contact: Vasil Velchev    +359 899973015   
Mhat Steva Marina Clin Card Recruiting
Varna, Bulgaria, 9010
Contact: Yoto Yotov    +359 887 308138   
Canada, Alberta
Univ of Alberta Hospital - 2E4.33 Recruiting
Edmonton, Alberta, Canada, T6G 2B7
Contact: Dale Lien    780-407-7359   
Canada, British Columbia
Hosp University of British Columbia - St. Paul'S Hospital Recruiting
Vancouver, British Columbia, Canada, V6Z 1Y6
Contact: Jasmine Grewal    604-806-8785      
Clinica Tabancura - Cardio Unit Recruiting
Santiago, Chile, 7650018
Contact: Pablo Sepulveda Varela    562-3954364   
Czech Republic
Fn Brno Bohunice Cardiology Recruiting
Brno, Czech Republic, 625 00
Contact: Jindřich Špinar    +420 532 232 601   
Gen Faculty Hosp Prague Cardiology Clin Recruiting
Praha 2, Czech Republic, 128 08
Contact: Pavel Jansa    + 420 728 717 041   
Hosp Na Homolce, Cardiology Dept. Recruiting
Praha 5, Czech Republic, 150 30
Contact: Jana Popelová    +420 257 273 041   
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 Cardiology Haut Leveque - Dept Congenital Diseases Recruiting
Pessac, France, 33604
Contact: Jean-Benoit Thambo    +33 5 57 65 64 65   
Herzzentrum Berlin, Ped Cardiology Not yet 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 Recruiting
München, Germany, 80636
Contact: Harald Kaemmerer    0049 (0) 89 1218 3006   
Semmelweis Univ - Pulmonology Not yet recruiting
Budapest, Hungary, 1125
Contact: Kristóf Karlócai    +36 1355 97 33 / ext.7018   
Gottsegen Gyorgy National Card Inst - Pediatric Card Not yet recruiting
Budapest, Hungary, 1096
Contact: András Szatmári    +36 70 382 0257   
Gottsegen Gyorgy National Card Inst - Adult Cardiology Recruiting
Budapest, Hungary, 1096
Contact: András Temesvári    +36 1 215 1220   
Univ of Szeged Clin Ctr - Ii Dept of Int Med and Cardio Ctr Recruiting
Szeged, Hungary, 6720
Contact: Tamás Forster    +36 62 -545-220, 545-819   
Sanjivani Hosp - Dept of Cardiology Not yet recruiting
Ahmedabad, India, 380015
Contact: Kamal Sharma    +91 79 2630 0411   
Apollo Hospitals Chennai Not yet recruiting
Chennai, India, 600006
Contact: Abraham Oomman    +91 9841174578   
Frontier Lifeline Hospitals, Pneumology Not yet recruiting
Chennai, India, 600101
Contact: Raghavan Subramanyan    91 97890 58553   
Care Hospitals Nampally, Cardio Dep. Hyderabad Not yet recruiting
Hyderabad, India, 500001
Contact: Bhagatuval Kutumba Srinivasa Sastry    91 98495 99888   
Care Hosp - Ped Cardio Dept Not yet recruiting
Hyderabad, India, 500 034
Contact: Nageswara Rao Koneti    +91 98495 92752   
Carmel Med Ctr - Pulm Unit Not yet recruiting
Haifa, Israel, 34362
Contact: Adir Yochai         
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 Recruiting
Pavia, Italy, 27100
Contact: Stefano Ghio    + 39 0382 503460   
Institut Jantung Negara Recruiting
Kuala Lumpur, Malaysia, 50400
Contact: David Chew    +60 3 2617 8444   
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 Not yet recruiting
Mexico City, Mexico, 06720
Contact: Julio Erdmenger Orellana    +525552289917   
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 Recruiting
Puebla, Mexico
Contact: Juan Carlos Perez Alba    +52.222.303.83.80      
Instituto de Corazon de Querètaro Recruiting
Querétaro, Mexico
Contact: Marco Alcocer    (442) 216-2745   
Amc Cardiology Recruiting
Amsterdam, Netherlands, 1100 DE
Contact: Barbara Mulder    (020) 566 3175   
Umc Groningen Ped Cardiology Recruiting
Groningen, Netherlands, 9713 GZ
Contact: Rolf M.F. Berger    +31-50-361 41 59   
PHC, MAB Recruiting
Manila, Philippines
Contact: Ma Paz B. Mateo    +639175329663      
Cardiology Gdańsk Univ Recruiting
Gdańsk, Poland, 80-952
Contact: Grzegorz Raczak    +48 58 349 39 10   
Cardiology Katowice Univ Recruiting
Katowice, Poland, 40-635
Contact: Zbigniew Gąsior    +48 32 359 88 84/5   
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   
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 Not yet recruiting
Bucuresti, Romania, 022328
Contact: Ioan Mircea Coman    +40 21 302 1110   
Clin Hosp For Inf and Pulm Dis Victor Babes - Ii Pulm Recruiting
Timisoara, Romania, 300312
Contact: Nicoleta Sorina Bertici    +40 256 20 76 70      
Cardio Med Srl Not yet recruiting
Tirgu-Mures, Romania, 540136
Contact: Rodica Toganel    +40 372 65 3100   
Russian Federation
V. A. Almazov Institute of Cardiology Recruiting
St Petersburg, Russian Federation, 194156
Contact: Olga M Moiseeva    + 78125528114 or + 79213068249   
Cardiology Scientific Research Institute Not yet recruiting
Tomsk, Russian Federation, 634012
Contact: Eugeniy Krivoschekov         
Clin Hosp Ctr Zemun - Cardiology Dept Recruiting
Belgrade, Serbia, 11080
Contact: Biljana Putniković    +381 11 3772 761   
Dedinje Cardiovasc Inst - Cardiovasc Research Ctr Recruiting
Belgrade, Serbia, 11040
Contact: Petar Otašević    +381 11 3601 669   
South Africa
Ufs Paediatric Cardiology Recruiting
Bloemfontein, South Africa, 9300
Contact: Stephen Brown    +27514053181   
Tread Research Recruiting
Cape Town, South Africa, 7505
Contact: Lesley Jean Burgess    +27 21 931 7825      
Principal Investigator: Phillipus Herbst, MD         
Chris Hani Baragwanath -Soweto Cardiovascular Recruiting
Johannesburg, South Africa, 2013
Contact: Mohammed Rafique Essop    +27 11 933-8145   
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 Recruiting
Madrid, Spain, 28007
Contact: Francisco Fernandez-Avilés Diaz    +34 91 586 80 00   
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 Recruiting
Kaohsiung, Taiwan, 813
Contact: Kai-Sheng Hsieh    + 886-7-342-2121 ext. 5002   
Taichung, Taiwan, 40705
Contact: Kuo-Yang Wang    886 4 2359 2525 # 3126      
National Taiwan Univ Hosp-Dept of Paed Recruiting
Taipei, Taiwan, 100
Contact: Hsao-Hsun Hsu    +886 2 2312 3456 ext.65913   
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   
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 Not yet recruiting
London, United Kingdom, SW3 6NP
Contact: Michael A. Gatzoulis    +44 20 73518602   
Manchester Royal Infirmary - Manchester Heart Centre Recruiting
Manchester, United Kingdom, M13 9WL
Contact: Viakom Mahadevan    +44 161 2763295   
Hanoi Medical University Hospital Recruiting
Hanoi, Vietnam
Contact: Nguyen Lan Hieu    84438522798   
Tam Duc Hospital Recruiting
Ho Chi Minh, Vietnam
Contact: Nguyen Vinh Pam    +84854110036   
Children's Hospital, Ho Chi Minh Not yet recruiting
Ho Chi Minh, Vietnam
Contact: Do Nguyen Tin         
Sponsors and Collaborators
  More Information

No publications provided

Responsible Party: Actelion Identifier: NCT01743001     History of Changes
Other Study ID Numbers: AC-055-305
Study First Received: November 29, 2012
Last Updated: April 14, 2014
Health Authority: Austria: Austrian Medicines and Medical Devices Agency
Belgium: Federal Agency for Medicinal Products and Health Products
Bulgaria: Bulgarian Drug Agency
Canada: Health Canada
Chile: Instituto de Salud Publica de Chile
China: Food and Drug Administration
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
India: Drugs Controller General of India
Israel: Ministry of Health
Italy: The Italian Medicines Agency
Malaysia: Ministry of Health
Mexico: Federal Commission for Protection Against Health Risks
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Philippines: Department of Health
Philippines : Food and Drug Administration
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Portugal: National Pharmacy and Medicines Institute
Russia: Ministry of Health of the Russian Federation
Serbia and Montenegro: Agency for Drugs and Medicinal Devices
South Africa: Medicines Control Council
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Taiwan: Department of Health
Turkey: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration
Vietnam: Ministry of Health

Keywords provided by Actelion:
Eisenmenger Syndrome

Additional relevant MeSH terms:
Eisenmenger Complex
Heart Defects, Congenital
Cardiovascular Abnormalities
Cardiovascular Diseases
Heart Diseases
Congenital Abnormalities processed this record on April 22, 2014