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CompletedNCT01743001MAESTROUpdated Feb 23, 2018Results posted

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

A Phase 3 interventional study of Macitentan 10 mg and Placebo in Pulmonary Arterial Hypertension, sponsored by Actelion. Completed at 55 sites in 21 countries. Open to participants aged 12 Years and older. Per ClinicalTrials.gov, last updated 2018-02-23.

Sponsored by Actelion (part of Johnson & Johnson) · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
226
Allocation
Randomized
Ages
12 Years and older
Sex
All
01

Study summary

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

02

Conditions studied

  • Pulmonary Arterial Hypertension

Keywords

  • exercise capacity
  • Eisenmenger Syndrome
03

In context

Pulmonary Arterial Hypertension

699 studies on the registry are indexed under Pulmonary Arterial Hypertension; 140 are open to participants now.

This study's enrollment of 226 is above the median of 40 across 477 interventional studies indexed under Pulmonary Arterial Hypertension.

Browse Pulmonary Arterial Hypertension studies →

Lead sponsor

Actelion is the lead sponsor of 143 studies on the registry; 1 is open to participants now.

Of its 28 completed or terminated interventional studies of FDA-regulated products, 25 (89%) have results posted.

First submitted before Actelion became part of Johnson & Johnson.

Browse Actelion studies →All Johnson & Johnson studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
12 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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., [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
Terms in these criteria, in plain language(1)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

FEV1

From a breathing test (spirometry): how much air you can blow out in the first second. Often given as a percentage of what is expected for your age, height and sex.

05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
226 participants (actual)

Study arms

  • Experimental
    Macitentan

    Subjects receive macitentan 10 mg oral tablet once daily

    Drug: Macitentan 10 mg

  • Placebo comparator
    Placebo

    Subjects receive macitentan-matching placebo oral tablet once daily

    Drug: Placebo

Interventions

  • DrugMacitentan 10 mg

    Macitentan 10 mg oral tablet once daily

    Also known as: ACT-064992

  • DrugPlacebo

    Macitentan-matching placebo oral tablet once daily

06

What researchers measure

Primary outcomes

  1. Change From Baseline to Week 16 in Exercise Capacity, as Measured by 6-minute Walk Distance (6MWD)

    The purpose of the six minute walk is to test exercise tolerance and capacity. The test measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes.

    Time frame: From baseline to Week 16

Secondary outcomes

  1. Change From Baseline to Week 16 in WHO Functional Class

    A shift in WHO functional classes is considered an 'improvement' when shifting to a lower class (e.g. from class III to class II) or a 'worsening' when shifting to a higher class (e.g. from class III to class IV). Definition of functional classes as follows - Class I: no symptoms with exercise or at rest. Class II: No symptoms at rest but uncomfortable and short of breath with normal activity such as climbing a flight of stairs, grocery shopping, or making the bed. Class III: May not have symptoms at rest but activities greatly limited by shortness of breath, fatigue, or near fainting (e.g. doing normal chores around the house, have to take breaks while doing activities of daily living). Class IV: Symptoms at rest and severe symptoms with any activity. Most patients also have edema in the feet and ankles as result of right heart failure.

    Time frame: From baseline to Week 16

  2. Change From Baseline to Week 16 in Dyspnea, Assessed by the Borg Dyspnea Index

    This outcome measures the difference in the Borg dyspnea index collected at the end of the 6-minute walk test (6MWT) at Week 16 compared to baseline. The Borg dyspnea index rates the severity of dyspnea (difficult or labored breathing) on a scale from 0 ('Nothing at all') to 10 ('Very, very severe - maximal'). A decrease in the Borg dyspnea index indicates an improvement.

    Time frame: From baseline to Week 16

  3. Change From Baseline to Week 16 in Quality of Life (QoL), Assessed by the Short Form-36 (SF-36) Questionnaire

    The SF-36 is a multi-purpose, short-form health survey with 36 questions. It yields an 8-scale profile of the functional health and well-being scores (i.e., physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health), as well as psychometrically based physical and mental health summary measures and a preference-based health utility (health rated as much better now than one year ago to much worse now than one year ago). It is a generic measure, as opposed to one that targets a specific age, disease, or treatment group. For each of the domains and scores that the SF36 measures an aggregate percentage score is produced. The percentage scores range from 0% (lowest or worst possible level of functioning) to 100% (highest or best possible level of functioning). A higher score for the individual domains and summary component scores indicates a better condition of the subject.

    Time frame: From baseline to Week 16

07

Results

Posted Jan 30, 2018

Participant flow

The study was conducted at 71 sites in 26 countries (geographical regions: Asia-Pacific, Eastern Europe, Latin America, North America, Western Europe including Israel and Turkey, and South Africa), of which 55 sites in 21 countries randomized subjects.

Participant flow — Overall Study
MilestoneMacitentanPlacebo
Started114112
Completed111112
Not completed30
Withdrew: Physician decision10
Withdrew: Pregnancy10
Withdrew: Death10

Outcome measures

PrimaryChange From Baseline to Week 16 in Exercise Capacity, as Measured by 6-minute Walk Distance (6MWD)

The purpose of the six minute walk is to test exercise tolerance and capacity. The test measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes.

Time frame:
From baseline to Week 16
Reported as:
Mean · meter
Change From Baseline to Week 16 in Exercise Capacity, as Measured by 6-minute Walk Distance (6MWD)
meterMacitentanPlacebo
6MWD at baseline368.7 ± 74.5380.3 ± 76.3
6MWD at Week 16387.1 ± 101.8399.9 ± 79.5
Change in 6MWD from baseline to Week 1618.3 ± 84.419.7 ± 53.0
Statistical analysis
  • Macitentan vs Placebo · ANCOVA · p = 0.6120 (To control for multiplicity across the primary and secondary endpoints, all secondary endpoints were analyzed hierarchically according to order and significance as pre-specified in the protocol eliminating further adjustment for multiple comparisons.) · Least-square (ls) mean difference: -4.7 · 95% CI -22.8 to 13.5ANCOVA model included treatment group, presence of DS (yes/no), and WHO FC (II vs III/IV) as categorical factors, and baseline 6MWD value as covariate
SecondaryChange From Baseline to Week 16 in WHO Functional Class

A shift in WHO functional classes is considered an 'improvement' when shifting to a lower class (e.g. from class III to class II) or a 'worsening' when shifting to a higher class (e.g. from class III to class IV). Definition of functional classes as follows - Class I: no symptoms with exercise or at rest. Class II: No symptoms at rest but uncomfortable and short of breath with normal activity such as climbing a flight of stairs, grocery shopping, or making the bed. Class III: May not have symptoms at rest but activities greatly limited by shortness of breath, fatigue, or near fainting (e.g. doing normal chores around the house, have to take breaks while doing activities of daily living). Class IV: Symptoms at rest and severe symptoms with any activity. Most patients also have edema in the feet and ankles as result of right heart failure.

Time frame:
From baseline to Week 16
Reported as:
Count of participants · Participants
Change From Baseline to Week 16 in WHO Functional Class
ParticipantsMacitentanPlacebo
WHO functional class 1 at Week 1631
WHO functional class 2 at Week 167279
WHO functional class 3 at Week 163832
WHO functional class 4 at Week 1610
Unchanged from baseline to Week 1610395
Improvement from baseline to Week 161016
Worsening from baseline to Week 1611
Statistical analysis
  • Macitentan vs Placebo · Regression, Logistic · p = 0.1450 (The secondary efficacy endpoints were analyzed hierarchically as this approach eliminated the requirement for further adjustment for multiple comparisons.) · Odds ratio (or): 0.53 · 95% CI 0.23 to 1.24Logistic regression model adjusted for randomized treatment group and location of cardiac defect (pre-tricupsid / post-tricupsid ) as factors.
SecondaryChange From Baseline to Week 16 in Dyspnea, Assessed by the Borg Dyspnea Index

This outcome measures the difference in the Borg dyspnea index collected at the end of the 6-minute walk test (6MWT) at Week 16 compared to baseline. The Borg dyspnea index rates the severity of dyspnea (difficult or labored breathing) on a scale from 0 ('Nothing at all') to 10 ('Very, very severe - maximal'). A decrease in the Borg dyspnea index indicates an improvement.

Time frame:
From baseline to Week 16
Reported as:
Mean · Score on a scale
Change From Baseline to Week 16 in Dyspnea, Assessed by the Borg Dyspnea Index
Score on a scaleMacitentanPlacebo
Borg dyspnea index score at baseline3.00 ± 1.952.94 ± 1.88
Borg dyspnea index score at Week 162.78 ± 2.102.66 ± 1.64
Change from baseline to Week 16-0.22 ± 1.56-0.29 ± 1.50
Statistical analysis
  • Macitentan vs Placebo · ANCOVA · p = 0.6818 (The secondary efficacy endpoints were analyzed hierarchically as this approach eliminated the requirement for further adjustment for multiple comparisons.) · Least-square (ls) mean difference: 0.08 · 95% CI -0.29 to 0.44Adjusted for randomized treatment group, location of cardiac defect(pre-tricupsid/post-tricupsid) as factors, baseline Borg dyspnea index as covariate
SecondaryChange From Baseline to Week 16 in Quality of Life (QoL), Assessed by the Short Form-36 (SF-36) Questionnaire

The SF-36 is a multi-purpose, short-form health survey with 36 questions. It yields an 8-scale profile of the functional health and well-being scores (i.e., physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health), as well as psychometrically based physical and mental health summary measures and a preference-based health utility (health rated as much better now than one year ago to much worse now than one year ago). It is a generic measure, as opposed to one that targets a specific age, disease, or treatment group. For each of the domains and scores that the SF36 measures an aggregate percentage score is produced. The percentage scores range from 0% (lowest or worst possible level of functioning) to 100% (highest or best possible level of functioning). A higher score for the individual domains and summary component scores indicates a better condition of the subject.

Time frame:
From baseline to Week 16
Reported as:
Mean · Score on a scale
Change From Baseline to Week 16 in Quality of Life (QoL), Assessed by the Short Form-36 (SF-36) Questionnaire
Score on a scaleMacitentanPlacebo
Domain score: physical functioning at baseline51.9 ± 21.852.7 ± 22.4
Domain score: physical functioning at Week 1656.4 ± 21.958.0 ± 19.7
Change in physical functioning (domain score)4.6 ± 16.55.3 ± 15.4
Domain score: role-physical at baseline46.2 ± 25.548.4 ± 27.9
Domain score: role-physical at Week 1652.8 ± 25.555.9 ± 25.3
Change in role-physical (domain score)6.6 ± 20.17.4 ± 22.1
Domain score: pain index at baseline61.7 ± 23.064.6 ± 24.6
Domain score: pain index at Week 1665.2 ± 23.666.2 ± 24.7
Change in pain index (domain score)3.5 ± 22.11.6 ± 27.1
Domain score:general health perceptions baseline36.1 ± 21.037.2 ± 19.8
Domain score:general health perceptions at Week 1640.3 ± 22.737.6 ± 20.3
Change in general health perceptions(domain score)4.2 ± 16.40.5 ± 15.5
Domain score: vitality at baseline49.0 ± 22.151.9 ± 21.5
Domain score: vitality at Week 1656.1 ± 19.856.3 ± 17.5
Change in vitality (domain score)7.1 ± 18.34.4 ± 18.2
Domain score: social functioning at baseline64.7 ± 26.866.9 ± 25.0
Domain score: social functioning at Week 1666.6 ± 25.869.2 ± 23.5
Change in social functioning (domain score)1.9 ± 23.02.3 ± 24.5
Domain score: role-emotional at baseline61.6 ± 27.461.3 ± 28.8
Domain score: role-emotional at Week 1663.3 ± 26.866.0 ± 25.6
Change in role-emotional (domain score)1.7 ± 22.84.7 ± 25.0
Domain score: mental health index at baseline63.8 ± 21.164.0 ± 20.5
Domain score: mental health index at Week 1665.7 ± 18.967.7 ± 20.6
Change in mental health index (domain score)1.9 ± 16.13.7 ± 16.6
Norm-based: physical functioning at baseline36.8 ± 9.237.1 ± 9.4
Norm-based: physical functioning at Week 1638.7 ± 9.239.3 ± 8.3
Change in physical functioning (norm-based)1.9 ± 6.92.2 ± 6.5
Norm-based: role-physical at baseline35.8 ± 10.036.6 ± 10.9
Norm-based: role-physical at Week 1638.4 ± 10.039.6 ± 9.9
Change in role-physical (norm-based)2.6 ± 7.92.9 ± 8.7
Norm-based: pain index at baseline45.9 ± 9.747.2 ± 10.4
Norm-based: pain index at Week 1647.4 ± 10.047.8 ± 10.4
Change in pain index (norm-based)1.5 ± 9.30.7 ± 11.5
Norm-based: general health perceptions at baseline33.4 ± 10.033.9 ± 9.4
Norm-based: general health perceptions at Week 1635.4 ± 10.834.2 ± 9.7
Change in general health perceptions (norm-based)2.0 ± 7.80.2 ± 7.4
Norm-based: vitality at baseline45.4 ± 11.146.8 ± 10.7
Norm-based: vitality at Week 1648.9 ± 9.949.0 ± 8.7
Change in vitality (norm-based)3.6 ± 9.12.2 ± 9.1
Norm-based: social functioning at baseline41.5 ± 11.742.4 ± 10.9
Norm-based: social functioning at Week 1642.3 ± 11.343.4 ± 10.3
Change in social functioning (norm-based)0.8 ± 10.01.0 ± 10.7
Norm-based: role-emotional at baseline37.9 ± 12.837.8 ± 13.4
Norm-based: role-emotional at Week 1638.8 ± 12.540.0 ± 11.9
Change in role-emotional (norm-based)0.8 ± 10.62.2 ± 11.7
Norm-based: mental health index at baseline43.7 ± 11.943.8 ± 11.6
Norm-based: mental health index at Week 1644.8 ± 10.645.9 ± 11.6
Change in mental health index (norm-based)1.1 ± 9.12.1 ± 9.3
Physical component summary score at baseline37.6 ± 7.538.6 ± 8.7
Physical component summary score at Week 1640.0 ± 8.440.0 ± 7.7
Change in physical component summary score2.4 ± 6.41.4 ± 6.5
Mental component summary score at baseline43.8 ± 12.444.1 ± 12.1
Mental component summary score at Week 1644.7 ± 11.745.9 ± 10.9
Change in mental component summary score1.0 ± 9.31.8 ± 9.3
Statistical analysis
  • Macitentan vs Placebo · ANCOVA · p = 0.6431 · Least-square (ls) mean difference: -1.0 · 95% CI -5.0 to 3.1Adjusted for randomized treatment group, location of cardiac defect (pre-tricupsid/post-tricupsid) as factors and baseline scores as covariates.
  • Macitentan vs Placebo · ANCOVA · p = 0.5988 · Least-square (ls) mean difference: -1.4 · 95% CI -6.7 to 3.9Adjusted for randomized treatment group, location of cardiac defect (pre-tricupsid/post-tricupsid) as factors and baseline scores as covariates.
  • Macitentan vs Placebo · ANCOVA · p = 0.9642 · Least-square (ls) mean difference: 0.1 · 95% CI -5.9 to 6.2Adjusted for randomized treatment group, location of cardiac defect (pre-tricupsid/post-tricupsid) as factors and baseline scores as covariates.
  • Macitentan vs Placebo · ANCOVA · p = 0.1542 · Least-square (ls) mean difference: 3.1 · 95% CI -1.2 to 7.3Adjusted for randomized treatment group, location of cardiac defect (pre-tricupsid/post-tricupsid) as factors and baseline scores as covariates.
  • Macitentan vs Placebo · ANCOVA · p = 0.6020 · Least-square (ls) mean difference: 1.1 · 95% CI -3.1 to 5.3Adjusted for randomized treatment group, location of cardiac defect (pre-tricupsid/post-tricupsid) as factors and baseline scores as covariates.
  • Macitentan vs Placebo · ANCOVA · p = 0.6340 · Least-square (ls) mean difference: -1.4 · 95% CI -7.2 to 4.4Adjusted for randomized treatment group, location of cardiac defect (pre-tricupsid/post-tricupsid) as factors and baseline scores as covariates.
  • Macitentan vs Placebo · ANCOVA · p = 0.3384 · Least-square (ls) mean difference: -2.8 · 95% CI -8.7 to 3.0Adjusted for randomized treatment group, location of cardiac defect (pre-tricupsid/post-tricupsid) as factors and baseline scores as covariates.
  • Macitentan vs Placebo · ANCOVA · p = 0.2704 · Least-square (ls) mean difference: -2.3 · 95% CI -6.4 to 1.8Adjusted for randomized treatment group, location of cardiac defect (pre-tricupsid/post-tricupsid) as factors and baseline scores as covariates.
  • Macitentan vs Placebo · ANCOVA · p = 0.6431 · Least-square (ls) mean difference: -0.4 · 95% CI -2.1 to 1.3Adjusted for randomized treatment group, location of cardiac defect (pre-tricupsid/post-tricupsid) as factors and baseline scores as covariates.
  • Macitentan vs Placebo · ANCOVA · p = 0.5988 · Least-square (ls) mean difference: -0.6 · 95% CI -2.6 to 1.5Adjusted for randomized treatment group, location of cardiac defect (pre-tricupsid/post-tricupsid) as factors and baseline scores as covariates.
  • Macitentan vs Placebo · ANCOVA · p = 0.9642 · Least-square (ls) mean difference: 0.1 · 95% CI -2.5 to 2.6Adjusted for randomized treatment group, location of cardiac defect (pre-tricupsid/post-tricupsid) as factors and baseline scores as covariates.
  • Macitentan vs Placebo · ANCOVA · p = 0.1542 · Least-square (ls) mean difference: 1.5 · 95% CI -0.6 to 3.5Adjusted for randomized treatment group, location of cardiac defect (pre-tricupsid/post-tricupsid) as factors and baseline scores as covariates.
  • Macitentan vs Placebo · ANCOVA · p = 0.6020 · Least-square (ls) mean difference: 0.6 · 95% CI -1.5 to 2.6Adjusted for randomized treatment group, location of cardiac defect (pre-tricupsid/post-tricupsid) as factors and baseline scores as covariates.
  • Macitentan vs Placebo · ANCOVA · p = 0.6340 · Least-square (ls) mean difference: -0.6 · 95% CI -3.1 to 1.9Adjusted for randomized treatment group, location of cardiac defect (pre-tricupsid/post-tricupsid) as factors and baseline scores as covariates.
  • Macitentan vs Placebo · ANCOVA · p = 0.3384 · Least-square (ls) mean difference: -1.3 · 95% CI -4.1 to 1.4Adjusted for randomized treatment group, location of cardiac defect (pre-tricupsid/post-tricupsid) as factors and baseline scores as covariates.
  • Macitentan vs Placebo · ANCOVA · p = 0.2704 · Least-square (ls) mean difference: -1.3 · 95% CI -3.6 to 1.0Adjusted for randomized treatment group, location of cardiac defect (pre-tricupsid/post-tricupsid) as factors and baseline scores as covariates.
  • Macitentan vs Placebo · ANCOVA · p = 0.4332 · Least-square (ls) mean difference: 0.7 · 95% CI -1.0 to 2.3Adjusted for randomized treatment group, location of cardiac defect (pre-tricupsid/post-tricupsid) as factors and baseline scores as covariates.
  • Macitentan vs Placebo · ANCOVA · p = 0.3416 · Least-square (ls) mean difference: -1.1 · 95% CI -3.4 to 1.2Adjusted for randomized treatment group, location of cardiac defect (pre-tricupsid/post-tricupsid) as factors and baseline scores as covariates.

Adverse events

Collected over A safety follow-up visit was required 30 days after end of treatment period at Week 16. Subjects who prematurely discontinued treatment prior to Week 16 were required to perform a premature end-of-treatment visit no later than 7 days after last dose of study treatment and then followed by the 30 day safety follow-up visit.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Macitentan1/114 (0.9%)7/114 (6.1%)31/114 (27.2%)
Placebo0/112 (0%)2/112 (1.8%)30/112 (26.8%)
Most frequent serious events
Most frequent serious events
EventMacitentanPlacebo
Right ventricular failureCardiac disorders3/1140/112
PneumoniaInfections and infestations2/1140/112
Atrial fibrillationCardiac disorders1/1141/112
Cardiac failure chronicCardiac disorders0/1141/112
Acute kidney injuryRenal and urinary disorders1/1140/112
DizzinessNervous system disorders1/1140/112
EndocarditisInfections and infestations1/1140/112
Respiratory failureRespiratory, thoracic and mediastinal disorders1/1140/112
Septic shockInfections and infestations1/1140/112
Transient ischaemic attackNervous system disorders1/1140/112
Most frequent other events
Most frequent other events
EventMacitentanPlacebo
NasopharyngitisInfections and infestations3/11414/112
HeadacheNervous system disorders13/1145/112
Upper respiratory tract infectionInfections and infestations11/1147/112
HaemoptysisRespiratory, thoracic and mediastinal disorders0/1146/112
BronchitisInfections and infestations6/1143/112

Baseline characteristics

Age, Continuous
Age, Continuous(Years)MacitentanPlaceboTotal
Median33.0 (12 to 82)31.0 (13 to 62)32.0 (12 to 82)
Age, Customized
Age, Customized(Participants)MacitentanPlaceboTotal
12 - 17 years13215
18 - 55 years90105195
≥ 56 years11516
Sex: Female, Male
Sex: Female, Male(Participants)MacitentanPlaceboTotal
Female8268150
Male324476
Region of Enrollment
Region of Enrollment(Participants)MacitentanPlaceboTotal
Asia-Pacific474491
Eastern Europe252752
Latin America191837
North America257
Western Europe - Israel211839
Body Mass Index (BMI)
Body Mass Index (BMI)(kg/m^2)MacitentanPlaceboTotal
Median21.15 (11.9 to 38.9)21.55 (14.5 to 42.2)21.35 (11.9 to 42.2)
WHO functional class
WHO functional class(Participants)MacitentanPlaceboTotal
class I000
class II6966135
class III454691
class IV000
08

Study locations

55 sites
  • Ahmanson/UCLA Heart Disease Center
    Los Angeles, California 90095, United States
  • Stanford Hospital and Clinic
    Palo Alto, California 94304, United States
  • Emory University Hospital/the Emory Clinic
    Atlanta, Georgia 30322, United States
  • Barnes-Jewish Hosp/Wash Univ School of Med
    Saint Louis, Missouri 63110, United States
  • Children'S Heart Center Nevada
    Las Vegas, Nevada 89109, United States
  • Nationwide Children's Hospital
    Columbus, Ohio 43210, United States
  • Texas Children'S Hosp - Dept of Cardiology
    Houston, Texas 77030-2303, United States
  • Gen Hosp Univ Vienna Dept Cardiology
    Vienna, A-1090, Austria
  • Mhat Nat Card Hosp - Cardiology Clinic
    Sofia, 1309, Bulgaria
  • Mhat Nat Card Hosp - Pediatric Clin / Ped Card Dept
    Sofia, 1309, Bulgaria
  • Mhat Sveta Anna Clin Card
    Sofia, 1750, Bulgaria
  • Inst Nat Torax, Unidad Cardiopatia Congenitas Del Adulto
    Providencia, Chile
  • Clinica Tabancura - Cardio Unit
    Santiago, 7650018, Chile
  • Guangdong General Hospital, Cardiology Dpt
    Guangzhou, Guangdong 510080, China
  • Wu Han Asia Heart Hosp
    Wuhan, Hubei 430022, China
  • The General Hosp of Shenyang Military Region
    Shenyang, Liaoning 110016, China
  • Beijing Anzhen Hospital, Cardiology Dpt
    Beijing, 100029, China
  • Cardiovascular Institute&Fuwai Hospital
    Beijing, 100037, China
  • Shanghai Pulmonary Hospital, Dept of Pulmonary Circulation
    Shanghai, 200433, China
  • Hosp La Timone - Dept Pediatric Cardiology
    Marseille Cedex 5, 13385, France
  • Hosp Laennec - Dept Cardiology
    Nantes Cedex 1, 44093, France
  • Hosp Pompidou - Dept Congenital Cardiac Diseases
    Paris Cedex 15, 75908, France
  • Hosp Cardiology Haut Leveque - Dept Congenital Diseases
    Pessac, 33604, France
  • Herzzentrum Berlin, Ped Cardiology
    Berlin, 13353, Germany
  • Universitätsklinikum Giessen - Pediatric Heart Center
    Giessen, 35392, Germany
  • Uni Heidelberg - Kinderkardiologie
    Heidelberg, D-69120, Germany
  • Ahepa University General Hospital
    Thessaloniki, 54636, Greece
  • Rabin Medical Centre - Pulmonology
    Petach Tikvah, 49100, Israel
  • Institut Jantung Negara
    Kuala Lumpur, 50400, Malaysia
  • Unidad de Investigacion Clin En Med, Sc (Udicem)
    Monterrey, Nuevo Leon 64718, Mexico
  • Instituto Nacional de Cardiologia (Inc) Ignacio Chavez
    Mexico City, 14080, Mexico
  • Instituto de Corazon de Querètaro
    Querétaro, Mexico
  • PHC, MAB
    Manila, Philippines
  • Cardiology Gdańsk Univ
    Gdańsk, 80-952, Poland
  • Cardiology Kraków Univ
    Krakow, 31-202, Poland
  • Cardiology Wrocław
    Wrocław, 51-124, Poland
  • Hosp Univ Coimbra - Dpt Cardiology
    Coimbra, 3000-075, Portugal
  • Hosp Sta Marta - Dept Cardiology
    Lisboa, 1169-024, Portugal
  • Er Inst For Cardvasc Dis "Prof Dr Cc Iliescu" - Card Ii
    Bucuresti, 022328, Romania
  • Cardio Med Srl
    Targu-Mures, 540136, Romania
  • Clin Hosp For Inf and Pulm Dis Victor Babes - Ii Pulm
    Timisoara, 300312, Romania
  • Sci Institute Systemic Problems Cardio Diseases Kemerovo
    Kemerovo, 650002, Russian Federation
  • Russian Cardiology Scientific and Production Complex
    Moscow, 121552, Russian Federation
  • V. A. Almazov Institute of Cardiology
    St Petersburg, 197341, Russian Federation
  • Dedinje Cardiovasc Inst - Cardiovasc Research Ctr
    Belgrade, 11040, Serbia
  • Mother and Child Health Care Inst "Dr Vukan Cupic"
    Belgrade, 11070, Serbia
  • Clin Hosp Ctr Zemun - Cardiology Dept
    Belgrade, 11080, Serbia
  • Hosp Univ Vall D'Hebron - Dpt Congenital Heart Disease Adult
    Barcelona, 08035, Spain
  • Hosp Univ Virgen Macarena - Dpt Cardiology
    Sevilla, 41007, Spain
  • Hosp Universitario La Fe Dpt Cardiology
    Valencia, 46009, Spain
  • Omu Pediatry
    Samsun, 55139, Turkey
  • Bristol Univ Hosp Congenital Heart Centre
    Bristol, BS2 8BJ, United Kingdom
  • Hanoi Medical University Hospital
    Hanoi, Vietnam
  • Children's Hospital, Ho Chi Minh
    Ho Chi Minh, Vietnam
  • Tam Duc Hospital
    Ho Chi Minh, Vietnam
09

References and documents

Publications

  • Gatzoulis MA, Landzberg M, Beghetti M, Berger RM, Efficace M, Gesang S, He J, Papadakis K, Pulido T, Galie N; MAESTRO Study Investigators. Evaluation of Macitentan in Patients With Eisenmenger Syndrome. Circulation. 2019 Jan 2;139(1):51-63. doi: 10.1161/CIRCULATIONAHA.118.033575. PubMed 30586694 ↗
10

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Ran from May 2013 to primary completion in Dec 2016, 42 months.

Results were first posted in Jan 2018, 1 year 1 month after primary completion.

Of 43 industry-sponsored phase 3 interventional studies under Pulmonary Arterial Hypertension, half reached primary completion within 50 months of starting (the median), counting those still running; a quarter within 31 and three quarters within 83. This study's 42 months is below that.

Counting every sponsor, half of 49 studies reached it within 50 months; a quarter within 31 and three quarters within 83.

How these figures are worked out, and which studies are left out of them.

Registered
Nov 29, 2012
First posted
Dec 6, 2012
StartActual
May 21, 2013
Primary completionActual
Dec 1, 2016
CompletionActual
Dec 1, 2016
Results first posted
Jan 30, 2018
Last update
Feb 23, 2018
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Feb 23, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01743001
Lead sponsor
Actelion
Responsible party
Sponsor
First posted
Dec 6, 2012
Start date
May 21, 2013
Primary completion
Dec 1, 2016
Completion
Dec 1, 2016
Results posted
Jan 30, 2018
Last update
Feb 23, 2018

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jan 2018. You cannot join it, but the record below documents what was studied.

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Discussion

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Studies of the drug tested here: Macitentan

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