MAESTRO (Macitentan in Eisenmenger Syndrome To Restore Exercise Capacity)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Actelion
Sponsor:
Information provided by (Responsible Party):
Actelion
ClinicalTrials.gov Identifier:
NCT01743001
First received: November 29, 2012
Last updated: April 28, 2014
Last verified: April 2014
  Purpose

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

  Eligibility

Ages Eligible for Study:   12 Years and older
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:

  • 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 ClinicalTrials.gov identifier: NCT01743001

  Show 93 Study Locations
Sponsors and Collaborators
Actelion
  More Information

No publications provided

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: April 28, 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
Heart Defects, Congenital
Cardiovascular Abnormalities
Cardiovascular Diseases
Heart Diseases
Congenital Abnormalities

ClinicalTrials.gov processed this record on July 23, 2014