Pulmonary Arterial HypertensionPhase 3MAESTRONCT01743001
Clinical Study to Evaluate the Effects of Macitentan on Exercise Capacity in Subjects With Eisenmenger Syndrome
A Phase 3 study testing Macitentan 10 mg in people with Pulmonary Arterial Hypertension, run by Actelion at 55 sites in 21 countries.
Trial summary
Clinical study to assess the efficacy, safety, and tolerability of macitentan in subjects with Eisenmenger Syndrome. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Pulmonary Arterial Hypertension
- What is being tested?
- Macitentan 10 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 226 participants
- Where
- 55 sitesin 21 countries
- Study dates
- 21 May 2013to 1 Dec 2016
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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):
- Established by echocardiography as:
- Large congenital shunting defect at atrial, ventricular or arterial level*
Show all 23Show fewer
- and right to left shunt or bi-directional shunt with prevalent right to left direction.
- 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.
Who cannot join
- 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
Show all 33Show fewer
- 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
Trial locations and contacts
55 sites in 21 countries.
55 sites in 21 countries
United States7 sites
Emory University Hospital/the Emory Clinic
Atlanta, Georgia, 30322
Nationwide Children's Hospital
Columbus, Ohio, 43210
Texas Children'S Hosp - Dept of Cardiology
Houston, Texas, 77030-2303
Children'S Heart Center Nevada
Las Vegas, Nevada, 89109
Ahmanson/UCLA Heart Disease Center
Los Angeles, California, 90095
Stanford Hospital and Clinic
Palo Alto, California, 94304
Barnes-Jewish Hosp/Wash Univ School of Med
St Louis, Missouri, 63110
China6 sites
Beijing Anzhen Hospital, Cardiology Dpt
Beijing, 100029
Cardiovascular Institute&Fuwai Hospital
Beijing, 100037
Guangdong General Hospital, Cardiology Dpt
Guangzhou, Guangdong, 510080
Shanghai Pulmonary Hospital, Dept of Pulmonary Circulation
Shanghai, 200433
The General Hosp of Shenyang Military Region
Shenyang, Liaoning, 110016
Wu Han Asia Heart Hosp
Wuhan, Hubei, 430022
France4 sites
Hosp La Timone - Dept Pediatric Cardiology
Marseille, 13385
Hosp Laennec - Dept Cardiology
Nantes, 44093
Hosp Pompidou - Dept Congenital Cardiac Diseases
Paris, 75908
Hosp Cardiology Haut Leveque - Dept Congenital Diseases
Pessac, 33604
Bulgaria3 sites
Mhat Nat Card Hosp - Cardiology Clinic
Sofia, 1309
Mhat Nat Card Hosp - Pediatric Clin / Ped Card Dept
Sofia, 1309
Mhat Sveta Anna Clin Card
Sofia, 1750
Germany3 sites
Herzzentrum Berlin, Ped Cardiology
Berlin, 13353
Universitätsklinikum Giessen - Pediatric Heart Center
Giessen, 35392
Uni Heidelberg - Kinderkardiologie
Heidelberg, D-69120
Mexico3 sites
Instituto Nacional de Cardiologia (Inc) Ignacio Chavez
Mexico City, 14080
Unidad de Investigacion Clin En Med, Sc (Udicem)
Monterrey, Nuevo León, 64718
Instituto de Corazon de Querètaro
Querétaro
Poland3 sites
Cardiology Gdańsk Univ
Gdansk, 80-952
Cardiology Kraków Univ
Krakow, 31-202
Cardiology Wrocław
Wroclaw, 51-124
Romania3 sites
Er Inst For Cardvasc Dis "Prof Dr Cc Iliescu" - Card Ii
Bucharest, 022328
Cardio Med Srl
Târgu Mureş, 540136
Clin Hosp For Inf and Pulm Dis Victor Babes - Ii Pulm
Timișoara, 300312
Russia3 sites
Sci Institute Systemic Problems Cardio Diseases Kemerovo
Kemerovo, 650002
Russian Cardiology Scientific and Production Complex
Moscow, 121552
V. A. Almazov Institute of Cardiology
Saint Petersburg, 197341
Serbia3 sites
Dedinje Cardiovasc Inst - Cardiovasc Research Ctr
Belgrade, 11040
Mother and Child Health Care Inst "Dr Vukan Cupic"
Belgrade, 11070
Clin Hosp Ctr Zemun - Cardiology Dept
Belgrade, 11080
Spain3 sites
Hosp Univ Vall D'Hebron - Dpt Congenital Heart Disease Adult
Barcelona, 08035
Hosp Univ Virgen Macarena - Dpt Cardiology
Seville, 41007
Hosp Universitario La Fe Dpt Cardiology
Valencia, 46009
Vietnam3 sites
Hanoi Medical University Hospital
Hanoi
Children's Hospital, Ho Chi Minh
Ho Chi Minh City
Tam Duc Hospital
Ho Chi Minh City
Chile2 sites
Inst Nat Torax, Unidad Cardiopatia Congenitas Del Adulto
Providencia
Clinica Tabancura - Cardio Unit
Santiago, 7650018
Portugal2 sites
Hosp Univ Coimbra - Dpt Cardiology
Coimbra, 3000-075
Hosp Sta Marta - Dept Cardiology
Lisbon, 1169-024
United Kingdom1 site
Bristol Univ Hosp Congenital Heart Centre
Bristol, BS2 8BJ
About this study
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
Clinical study to assess the efficacy, safety, and tolerability of macitentan in subjects with Eisenmenger Syndrome.
- Conditions
- Pulmonary Arterial Hypertension
- Being tested
- Macitentan 10 mg, Placebo
- Keywords
- exercise capacity, Eisenmenger Syndrome
- Medical subject headings
- Pulmonary Arterial Hypertension, Eisenmenger Complex
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Macitentan 10 mgDrug
Also called ACT-064992
Macitentan 10 mg oral tablet once daily
PlaceboDrug
Macitentan-matching placebo oral tablet once daily
| Study group | Role | What they receive |
|---|---|---|
| Macitentan | Experimental | Subjects receive macitentan 10 mg oral tablet once daily Receives: Drug: Macitentan 10 mg |
| Placebo | Placebo comparator | Subjects receive macitentan-matching placebo oral tablet once daily Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From baseline to Week 16
Secondary outcomes (3)
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.
Measured: From baseline to Week 16
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.
Measured: From baseline to Week 16
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.
Measured: From baseline to Week 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2012 (estimated)
- Study start21 May 2013
- Primary completion1 Dec 2016
- Study completion1 Dec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 226 participants (actual)
Sponsor and investigators
- Lead sponsor
- Actelion
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01743001
- Sponsor's protocol ID
- AC-055-305
- Acronym
- MAESTRO
- Status last verified
- Jan 2018
- First submitted
- 29 Nov 2012
- Last updated
- 23 Feb 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01743001
- Acronym / sponsor ID
- MAESTRO / AC-055-305
- Conditions
- Pulmonary Arterial Hypertension
- Keywords
- exercise capacity, Eisenmenger Syndrome
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 226 participants (actual)
- Lead sponsor
- ActelionIndustry (pharma, biotech, devices)
- Study start
- 21 May 2013 (actual)
- Primary completion
- 1 Dec 2016 (actual)
- Study completion
- 1 Dec 2016 (actual)
- First posted
- 6 Dec 2012 (estimated)
- Results
- Posted 30 Jan 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Clinical study to assess the efficacy, safety, and tolerability of macitentan in subjects with Eisenmenger Syndrome.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Macitentan | Experimental | Drug: Macitentan 10 mgSubjects receive macitentan 10 mg oral tablet once daily |
| Placebo | Placebo comparator | Drug: PlaceboSubjects receive macitentan-matching placebo oral tablet once daily |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (23 listed)
- Subjects:
- Subjects (including those with Down Syndrome [DS]) with confirmed Eisenmenger Syndrome [ES] (European Society of Cardiology [ESC] and the European Respiratory Society [ERS] guidelines):
- 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)
Key exclusion criteria (33 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Macitentan 10 mgAlso: ACT-064992Macitentan 10 mg oral tablet once daily | Drug | Macitentan |
| PlaceboMacitentan-matching placebo oral tablet once daily | Drug | Placebo |
Primary outcome
Change From Baseline to Week 16 in Exercise Capacity, as Measured by 6-minute Walk Distance (6MWD)
Time frame: From baseline to Week 16
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.
3 secondary outcomes
Change From Baseline to Week 16 in WHO Functional Class
Time frame: From baseline to Week 16
Change From Baseline to Week 16 in Dyspnea, Assessed by the Borg Dyspnea Index
Time frame: From baseline to Week 16
Change From Baseline to Week 16 in Quality of Life (QoL), Assessed by the Short Form-36 (SF-36) Questionnaire
Time frame: From baseline to Week 16
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30586694Gatzoulis 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
55 sites in 21 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Macitentan 10 mg in people with Pulmonary Arterial Hypertension, run by Actelion at 55 sites in 21 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 55 sites in United States, China, France, Bulgaria, Germany and 16 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Jan 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline to Week 16 in Exercise Capacity, as Measured by 6-minute Walk Distance (6MWD) (time frame: From baseline to Week 16). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01743001, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2018.