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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Actelion
ClinicalTrials.gov Identifier:
NCT01743001
First received: November 29, 2012
Last updated: September 16, 2016
Last verified: September 2016
  Purpose
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: December 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

  Eligibility

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

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 ClinicalTrials.gov identifier: NCT01743001

  Hide Study Locations
Locations
United States, California
Ahmanson/UCLA Heart Disease Center
Los Angeles, California, United States, 90095
Stanford Hospital and Clinic
Palo Alto, California, United States, 94304
United States, Georgia
Emory University Hospital/the Emory Clinic
Atlanta, Georgia, United States, 30322
United States, Missouri
Barnes-Jewish Hosp/Wash Univ School of Med
St. Louis, Missouri, United States, 63110
United States, Nevada
Children'S Heart Center Nevada
Las Vegas, Nevada, United States, 89109
United States, Ohio
Nationwide Children's Hospital
Columbus, Ohio, United States, 43210
United States, Texas
Texas Children'S Hosp - Dept of Cardiology
Houston, Texas, United States, 77030-2303
Austria
Gen Hosp Univ Vienna Dept Cardiology
Vienna, Austria, A-1090
Bulgaria
Mhat Nat Card Hosp - Cardiology Clinic
Sofia, Bulgaria, 1309
Mhat Nat Card Hosp - Pediatric Clin / Ped Card Dept
Sofia, Bulgaria, 1309
Mhat Sveta Anna Clin Card
Sofia, Bulgaria, 1750
Chile
Inst Nat Torax, Unidad Cardiopatia Congenitas Del Adulto
Providencia, Chile
Clinica Tabancura - Cardio Unit
Santiago, Chile, 7650018
China, Guangdong
Guangdong General Hospital, Cardiology Dpt
Guangzhou, Guangdong, China, 510080
China, Hubei
Wu Han Asia Heart Hosp
Wuhan, Hubei, China, 430022
China, Liaoning
The General Hosp of Shenyang Military Region
Shenyang, Liaoning, China, 110016
China
Beijing Anzhen Hospital, Cardiology Dpt
Beijing, China, 100029
Cardiovascular Institute&Fuwai Hospital
Beijing, China, 100037
Shanghai Pulmonary Hospital, Dept of Pulmonary Circulation
Shanghai, China, 200433
France
Hosp La Timone - Dept Pediatric Cardiology
Marseille Cedex 5, France, 13385
Hosp Laennec - Dept Cardiology
Nantes Cedex 1, France, 44093
Hosp Pompidou - Dept Congenital Cardiac Diseases
Paris Cedex 15, France, 75908
Hosp Cardiology Haut Leveque - Dept Congenital Diseases
Pessac, France, 33604
Germany
Herzzentrum Berlin, Ped Cardiology
Berlin, Germany, 13353
Universitätsklinikum Giessen - Pediatric Heart Center
Giessen, Germany, 35392
Uni Heidelberg - Kinderkardiologie
Heidelberg, Germany, D-69120
Greece
Ahepa University General Hospital
Thessaloniki, Greece, 54636
Israel
Rabin Medical Centre - Pulmonology
Petach Tikvah, Israel, 49100
Malaysia
Institut Jantung Negara
Kuala Lumpur, Malaysia, 50400
Mexico
Unidad de Investigacion Clin En Med, Sc (Udicem)
Monterrey, Nuevo Leon, Mexico, 64718
Instituto Nacional de Cardiologia (Inc) Ignacio Chavez
Mexico City, Mexico, 14080
Instituto de Corazon de Querètaro
Querétaro, Mexico
Philippines
PHC, MAB
Manila, Philippines
Poland
Cardiology Gdańsk Univ
Gdańsk, Poland, 80-952
Cardiology Kraków Univ
Krakow, Poland, 31-202
Cardiology Wrocław
Wrocław, Poland, 51-124
Portugal
Hosp Univ Coimbra - Dpt Cardiology
Coimbra, Portugal, 3000-075
Hosp Sta Marta - Dept Cardiology
Lisboa, Portugal, 1169-024
Romania
Er Inst For Cardvasc Dis "Prof Dr Cc Iliescu" - Card Ii
Bucuresti, Romania, 022328
Cardio Med Srl
Targu-Mures, Romania, 540136
Clin Hosp For Inf and Pulm Dis Victor Babes - Ii Pulm
Timisoara, Romania, 300312
Russian Federation
Sci Institute Systemic Problems Cardio Diseases Kemerovo
Kemerovo, Russian Federation, 650002
Russian Cardiology Scientific and Production Complex
Moscow, Russian Federation, 121552
V. A. Almazov Institute of Cardiology
St Petersburg, Russian Federation, 197341
Serbia
Dedinje Cardiovasc Inst - Cardiovasc Research Ctr
Belgrade, Serbia, 11040
Mother and Child Health Care Inst "Dr Vukan Cupic"
Belgrade, Serbia, 11070
Clin Hosp Ctr Zemun - Cardiology Dept
Belgrade, Serbia, 11080
Spain
Hosp Univ Vall D'Hebron - Dpt Congenital Heart Disease Adult
Barcelona, Spain, 08035
Hosp Univ Virgen Macarena - Dpt Cardiology
Sevilla, Spain, 41007
Hosp Universitario La Fe Dpt Cardiology
Valencia, Spain, 46009
Turkey
Omu Pediatry
Samsun, Turkey, 55139
United Kingdom
Bristol Univ Hosp Congenital Heart Centre
Bristol, United Kingdom, BS2 8BJ
Vietnam
Hanoi Medical University Hospital
Hanoi, Vietnam
Children's Hospital, Ho Chi Minh
Ho Chi Minh, Vietnam
Tam Duc Hospital
Ho Chi Minh, Vietnam
Sponsors and Collaborators
Actelion
  More Information

Responsible Party: Actelion
ClinicalTrials.gov Identifier: NCT01743001     History of Changes
Other Study ID Numbers: AC-055-305 
Study First Received: November 29, 2012
Last Updated: September 16, 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:
Syndrome
Hypertension
Familial Primary Pulmonary Hypertension
Eisenmenger Complex
Disease
Pathologic Processes
Vascular Diseases
Cardiovascular Diseases
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases
Heart Defects, Congenital
Cardiovascular Abnormalities
Heart Diseases
Congenital Abnormalities
Macitentan
Endothelin A Receptor Antagonists
Endothelin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Endothelin B Receptor Antagonists

ClinicalTrials.gov processed this record on September 29, 2016