MAESTRO (Macitentan in Eisenmenger Syndrome To Restore Exercise Capacity)

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2014 by Actelion
Information provided by (Responsible Party):
Actelion Identifier:
First received: November 29, 2012
Last updated: December 4, 2014
Last verified: December 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, 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: 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: March 2016
Estimated Primary Completion Date: February 2016 (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 and older
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:

  • ASD
  • VSD
  • partial or complete AVSD
  • PDA
  • AP window
  • 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:

    • 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 reliably perform the 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., TLC < 60% of predicted value) or obstructive lung disease (i.e., FEV1 < 80 % of predicted value, and FEV1 / 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 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

  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 - 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 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   
Gottsegen Gyorgy National Card Inst - Adult Cardiology Recruiting
Budapest, Hungary, 1096
Contact: András Temesvári    +36 1 215 1220   
Gottsegen Gyorgy National Card Inst - Pediatric Card Not yet recruiting
Budapest, Hungary, 1096
Contact: András Szatmári    +36 70 382 0257   
Semmelweis Univ - Pulmonology Not yet recruiting
Budapest, Hungary, 1125
Contact: Kristóf Karlócai    +36 1355 97 33 / ext.7018   
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   
Frontier Lifeline Hospitals, Pneumology Not yet recruiting
Chennai, India, 600101
Contact: Raghavan Subramanyan    91 97890 58553   
Apollo Hospitals Chennai Not yet recruiting
Chennai, India, 600006
Contact: Abraham Oomman    +91 9841174578   
Care Hosp - Ped Cardio Dept Not yet recruiting
Hyderabad, India, 500 034
Contact: Nageswara Rao Koneti    +91 98495 92752   
Care Hospitals Nampally, Cardio Dep. Hyderabad Not yet recruiting
Hyderabad, India, 500001
Contact: Bhagatuval Kutumba Srinivasa Sastry    91 98495 99888   
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 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 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   
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 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   
Gazi University Recruiting
Ankara, Turkey, 06500
Contact: Sedef Tunaoglu    90312 202 6129      
Hacettepe Unv. Dept. of Pediatry Recruiting
Ankara, Turkey, 06100
Contact: DURSUN ALEHAN    +90312 305 1157   
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   
Children's Hospital, Ho Chi Minh Not yet recruiting
Ho Chi Minh, Vietnam
Contact: Do Nguyen Tin         
Tam Duc Hospital Recruiting
Ho Chi Minh, Vietnam
Contact: Nguyen Vinh Pam    +84854110036   
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: December 4, 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 Pública 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
Cardiovascular Abnormalities
Cardiovascular Diseases
Congenital Abnormalities
Heart Defects, Congenital
Heart Diseases processed this record on March 31, 2015