MAESTRO (Macitentan in Eisenmenger Syndrome To Restore Exercise Capacity)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Actelion
Sponsor:
Information provided by (Responsible Party):
Actelion
ClinicalTrials.gov Identifier:
NCT01743001
First received: November 29, 2012
Last updated: August 7, 2014
Last verified: August 2014

November 29, 2012
August 7, 2014
May 2013
February 2016   (final data collection date for primary outcome measure)
Change from baseline to Week 16 in exercise capacity, as measured by 6MWD [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01743001 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
MAESTRO (Macitentan in Eisenmenger Syndrome To Restore Exercise Capacity)
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.

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

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Eisenmenger Syndrome
  • 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
  • Drug: Matching placebo oral tablet, to be taken once daily.
    Matching placebo oral tablet, to be taken once daily.
    Other Name: Placebo
  • Experimental: Macitentan
    Macitentan 10 mg, oral tablet, to be taken once daily.
    Intervention: Drug: Macitentan 10 mg, oral tablet, to be taken once daily.
  • Placebo Comparator: Placebo
    Matching placebo oral tablet, to be taken once daily.
    Intervention: Drug: Matching placebo oral tablet, to be taken once daily.
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
220
March 2016
February 2016   (final data collection date for primary outcome measure)

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.
Both
12 Years and older
No
United States,   Netherlands,   India,   United Kingdom,   Romania,   Poland,   Russian Federation,   Israel,   Vietnam,   South Africa,   Serbia,   Chile,   Germany,   Czech Republic,   Turkey,   Austria,   Hungary,   France,   Italy,   Portugal,   Spain,   Canada,   Mexico,   Malaysia,   Taiwan,   Bulgaria,   Philippines,   Belgium
 
NCT01743001
AC-055-305
Yes
Actelion
Actelion
Not Provided
Not Provided
Actelion
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP