Congenital Heart DiseasePhase 3RUBATONCT03153137
Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects
A Phase 3 study testing Macitentan 10 mg in people with Congenital Heart Disease, run by Actelion at 32 sites in 12 countries.
Trial summary
The primary objective is to assess the effect of macitentan 10 mg as compared to placebo on exercise capacity through cardiopulmonary exercise testing. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Congenital Heart Disease
- 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
- 142 participants
- Where
- 32 sitesin 12 countries
- Study dates
- 14 Aug 2017to 26 Jul 2021
- 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
- Written informed consent/assent from the subject and/or a legal representative prior to initiation of any study-mandated procedures
- Fontan-palliated subjects with either intra-atrial lateral tunnel total cavopulmonary connection (LT-TCPC), or extra cardiac tunnel TCPC (EC-TCPC) surgery > 1 year before Screening. Either LT- or EC-TCPC can be primary or secondary to atrio-pulmonary connection
- New York Heart Association (NYHA) functional class (FC) II or III (assessed by the investigator using the Specific Activity Scale
- Women of childbearing potential must have a negative serum pregnancy test use reliable contraception
Who cannot join
- Pattern of Fontan circulation severity
- Deterioration of the Fontan-palliated condition.
- Limitations to Cardiopulmonary exercise testing (CPET)
- Peak VO2 < 15 mL/kg/min.
- Any known factor or disease that may interfere with treatment compliance or full participation in the study
Trial locations and contacts
32 sites in 12 countries.
32 sites in 12 countries
United States6 sites
University of Alabama at Birmingham
Birmingham, Alabama, 35233-1935
Massachusetts General Hospital Heart Center
Boston, Massachusetts, 02114
Nationwide Children's Hospital
Columbus, Ohio, 43205
Texas Children's Hospital
Houston, Texas, 77030-2303
UCLA
Los Angeles, California, 90095
Providence Medical Research Providence Health Care
Spokane, Washington, 99202
Australia6 sites
Royal Adelaide Hospital
Adelaide, 5000
Royal Prince Alfred Hospital
Camperdown, 2050
The Prince Charles Hospital, Adult Congenital Heart Disease Unit
Chermside, 4032
Royal Children's Hospital
Parkville, 3052
Queensland CHILDREN'S HOSPITAL
South Brisbane, 4101
Westmead Hospital
Westmead, 2145
China4 sites
Beijing Anzhen Hospital
Beijing, 100029
Beijing Fuwai Hospital
Beijing, 100037
Shanghai Childrens Medical Center
Shanghai, 200127
Wuhan Asia Heart Hospital
Wuhan, 430022
Poland4 sites
Uniwersyteckie Centrum Kliniczne
Gdansk, 80 952
Uniwersytecki Szpital Dzieciecy w Krakowie
Krakow, 30-663
Krakowski Szpital Specjalityczny im Jana Pawla II Oddzial Kliniczny Chorob Serca i Naczyn
Krakow, 31 202
Wojewodzki Szpital Specjalistyczny We Wroclawiu
Wroclaw, 51 124
France3 sites
CHU Arnaud de Villeneuve
Montpellier, 34295
Hôpital Necker - Enfants Malades
Paris, 75015
Hôpital Cardiologique Du Haut-Lévêque
Pessac, 33604
Germany2 sites
Deutsches Herzzentrum Berlinklinik Für Angeborene Herzfehler
Berlin, 13353
Deutsches Herzzentrum München
München, 80636
United Kingdom2 sites
Queen Elizabeth Hospital
Birmingham, B15 2TH
Birmingham Children's Hospital
Birmingham, B4 6NH
About this study
Official title: Prospective, Multi-center, Double-blind, Randomized, Placebo-controlled, Parallel-group Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Adult and Adolescent Subjects
The primary objective is to assess the effect of macitentan 10 mg as compared to placebo on exercise capacity through cardiopulmonary exercise testing.
- Conditions
- Congenital Heart Disease
- Being tested
- Macitentan 10 mg, Placebo
- Medical subject headings
- Heart Defects, Congenital
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Macitentan 10 mgDrug
film-coated tablet; oral use
PlaceboDrug
film-coated tablet; oral use
| Study group | Role | What they receive |
|---|---|---|
| Macitentan | Experimental | Macitentan 10 mg per day; film-coated tablet; oral use Receives: Drug: Macitentan 10 mg |
| Placebo | Placebo comparator | film-coated tablet; oral use Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Peak Oxygen Uptake/Consumption (VO2) Up to Week 16
Change from baseline in peak VO2 up to Week 16 was reported.
Measured: Baseline up to Week 16
Secondary outcomes (26)
Change From Baseline in Peak VO2 Up to Week 52
Change from baseline in peak VO2 up to Week 52 was reported.
Measured: Baseline up to Week 52
Change From Baseline in Mean Count Per Minute of Daily Physical Activity Measured by Accelerometer (PA-Ac) Up to Week 16
Change from baseline in mean count per minute of daily PA-Ac up to Week 16 was reported. The daily physical activity (counts per min) of the participant was assessed via accelerometer during daytime. The accelerometer was given to the participant at Visit 1, and data was collected for 9 consecutive daily daytime periods after Visit 1 (baseline) to Visit 4 (Week 16).
Measured: Baseline up to Week 16
Number of Participants With Treatment-emergent Serious Adverse Events (SAEs)
SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.
Measured: Up to 56 weeks
Number of Participants With Treatment-emergent Adverse Events (AEs)
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Measured: Up to 56 weeks
Number of Participants With AEs Leading to Premature Discontinuation of Study Treatment
Number of participants with AEs leading to premature discontinuation of study treatment was reported. AEs leading to premature discontinuation of study treatment were those with action taken with study drug reported as 'permanently discontinued' by the investigator.
Measured: Up to 56 weeks
Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP)
Change from baseline in systolic and diastolic arterial BP at Week 8, Week 16, Week 32 and Week 52 was reported.
Measured: Baseline, Week 8, Week 16, Week 32 and Week 52
Change From Baseline in Pulse Rate
Change from baseline in pulse rate at Week 8, Week 16, Week 32 and Week 52 was reported.
Measured: Baseline, Week 8, Week 16, Week 32 and Week 52
Change From Baseline in Oxygen Saturation (SpO2)
Change from baseline in SpO2 was reported.
Measured: Baseline, Week 8, Week 16, Week 32 and Week 52
Change From Baseline in Body Weight
Change from baseline in body weight was reported.
Measured: Baseline, Week 8, Week 16, Week 32 and Week 52
Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Values
Number of participants with treatment-emergent markedly laboratory abnormal laboratory values were reported. Abnormal values for platelets (LL < 75); Lymphocytes (HH > 4.0); Neutrophils (LL < 1.5); Prothrombin International Normalized Ratio: HH (greater than and equal to [>=] 1.5 upper limit of normal [ULN]), Ratio: HH >= 2.5 ULN); Bilirubin (HH >= 2 ULN); Alkaline Phosphatase (HH > 2.5 ULN); Glomerular Filtration Rate (LL < 60); Glucose (HH > 8.9); Triglycerides (HH > 3.42). Here "HH" refers to values above the normal range, where H stands for "high" and "LL" refers to values below the normal range where L stands for "low".
Measured: Up to 56 weeks
Change From Baseline in Hemoglobin
Change from baseline in hemoglobin was reported.
Measured: Baseline, Week 8, Week 16, Week 32 and Week 52
Change From Baseline in Hematocrit
Change from baseline in hematocrit was reported.
Measured: Baseline, Week 8, Week 16, Week 32 and Week 52
Change From Baseline in Erythrocytes and Reticulocytes
Change from baseline in erythrocytes and reticulocytes at Week 8, Week 16, Week 32 and Week 52 was reported.
Measured: Baseline, Week 8, Week 16, Week 32 and Week 52
Change From Baseline in Leucocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Platelets
Change from baseline in leucocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils and platelets at Week 8, Week 16, Week 32 and Week 52 was reported.
Measured: Baseline, Week 8, Week 16, Week 32 and Week 52
Change From Baseline in Prothrombin Time
Change from baseline in prothrombin time was reported.
Measured: Baseline, Week 8, Week 16, Week 32 and Week 52
Change From Baseline in Prothrombin International Normalized Ratio
Change from baseline in prothrombin international normalized ratio was reported.
Measured: Baseline, Week 8, Week 16, Week 32 and Week 52
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (AP)
Change from baseline in ALT, AST and AP were reported.
Measured: Baseline, Week 8, Week 16, Week 32 and Week 52
Change From Baseline in Bilirubin and Direct Bilirubin
Change from baseline in bilirubin and direct bilirubin was reported.
Measured: Baseline, Week 8, Week 16, Week 32 and Week 52
Change From Baseline in Gamma Glutamyl Transferase
Change from baseline in gamma glutamyl transferase was reported.
Measured: Baseline, Week 8, Week 16, Week 32 and Week 52
Change From Baseline in Creatinine
Change from baseline in creatinine was reported.
Measured: Baseline, Week 8, Week 16, Week 32 and Week 52
Change From Baseline in Urea Nitrogen
Change from baseline in urea nitrogen was reported.
Measured: Baseline, Week 8, Week 16, Week 32 and Week 52
Change From Baseline in Urate
Change from baseline in urate was reported.
Measured: Baseline, Week 8, Week 16, Week 32 and Week 52
Change From Baseline in Glucose, Cholesterol, Triglycerides, Sodium, Potassium, Chloride and Calcium
Change from baseline in glucose, cholesterol, triglycerides, sodium, potassium, chloride and calcium was reported.
Measured: Baseline, Week 8, Week 16, Week 32 and Week 52
Change From Baseline in Albumin and Protein
Change from baseline in albumin and protein was reported.
Measured: Baseline, Week 8, Week 16, Week 32 and Week 52
Change From Baseline in Alpha Fetoprotein
Change from baseline in alpha fetoprotein was reported.
Measured: Baseline, Week 8, Week 16, Week 32 and Week 52
Change From Baseline in Cystatin C
Change from baseline in cystatin C was reported.
Measured: Baseline, Week 8, Week 16, Week 32 and Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2017
- Study start14 Aug 2017
- Primary completion30 Jun 2021
- Study completion26 Jul 2021
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.
- Other trials for Congenital Heart DiseaseStudies 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
- 142 participants (actual)
Sponsor and investigators
- Lead sponsor
- Actelion
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03153137
- Sponsor's protocol ID
- AC-055H301
- Other IDs
- 2016-003320-23, 2016
- Acronym
- RUBATO
- Status last verified
- Mar 2025
- First submitted
- 12 May 2017
- Last updated
- 30 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective, Multi-center, Double-blind, Randomized, Placebo-controlled, Parallel-group Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Adult and Adolescent Subjects
- ClinicalTrials.gov ID
- NCT03153137
- Acronym / sponsor ID
- RUBATO / AC-055H301
- Conditions
- Congenital Heart Disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 142 participants (actual)
- Lead sponsor
- ActelionIndustry (pharma, biotech, devices)
- Study start
- 14 Aug 2017 (actual)
- Primary completion
- 30 Jun 2021 (actual)
- Study completion
- 26 Jul 2021 (actual)
- First posted
- 15 May 2017 (actual)
- Results
- Posted 13 Sep 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective is to assess the effect of macitentan 10 mg as compared to placebo on exercise capacity through cardiopulmonary exercise testing.
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 mgMacitentan 10 mg per day; film-coated tablet; oral use |
| Placebo | Placebo comparator | Drug: Placebofilm-coated tablet; oral use |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Written informed consent/assent from the subject and/or a legal representative prior to initiation of any study-mandated procedures
- Fontan-palliated subjects with either intra-atrial lateral tunnel total cavopulmonary connection (LT-TCPC), or extra cardiac tunnel TCPC (EC-TCPC) surgery > 1 year before Screening. Either LT- or EC-TCPC can be primary or secondary to atrio-pulmonary connection
- New York Heart Association (NYHA) functional class (FC) II or III (assessed by the investigator using the Specific Activity Scale
- Women of childbearing potential must have a negative serum pregnancy test use reliable contraception
Key exclusion criteria (5 listed)
- Pattern of Fontan circulation severity
- Deterioration of the Fontan-palliated condition.
- Limitations to Cardiopulmonary exercise testing (CPET)
- Peak VO2 < 15 mL/kg/min.
- Any known factor or disease that may interfere with treatment compliance or full participation in the study
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 mgfilm-coated tablet; oral use | Drug | Macitentan |
| Placebofilm-coated tablet; oral use | Drug | Placebo |
Primary outcome
Change From Baseline in Peak Oxygen Uptake/Consumption (VO2) Up to Week 16
Time frame: Baseline up to Week 16
Change from baseline in peak VO2 up to Week 16 was reported.
26 secondary outcomes
Change From Baseline in Peak VO2 Up to Week 52
Time frame: Baseline up to Week 52
Change From Baseline in Mean Count Per Minute of Daily Physical Activity Measured by Accelerometer (PA-Ac) Up to Week 16
Time frame: Baseline up to Week 16
Number of Participants With Treatment-emergent Serious Adverse Events (SAEs)
Time frame: Up to 56 weeks
Number of Participants With Treatment-emergent Adverse Events (AEs)
Time frame: Up to 56 weeks
Number of Participants With AEs Leading to Premature Discontinuation of Study Treatment
Time frame: Up to 56 weeks
Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP)
Time frame: Baseline, Week 8, Week 16, Week 32 and Week 52
Change From Baseline in Pulse Rate
Time frame: Baseline, Week 8, Week 16, Week 32 and Week 52
Change From Baseline in Oxygen Saturation (SpO2)
Time frame: Baseline, Week 8, Week 16, Week 32 and Week 52
Change From Baseline in Body Weight
Time frame: Baseline, Week 8, Week 16, Week 32 and Week 52
Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Values
Time frame: Up to 56 weeks
Change From Baseline in Hemoglobin
Time frame: Baseline, Week 8, Week 16, Week 32 and Week 52
Change From Baseline in Hematocrit
Time frame: Baseline, Week 8, Week 16, Week 32 and Week 52
Change From Baseline in Erythrocytes and Reticulocytes
Time frame: Baseline, Week 8, Week 16, Week 32 and Week 52
Change From Baseline in Leucocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Platelets
Time frame: Baseline, Week 8, Week 16, Week 32 and Week 52
Change From Baseline in Prothrombin Time
Time frame: Baseline, Week 8, Week 16, Week 32 and Week 52
Change From Baseline in Prothrombin International Normalized Ratio
Time frame: Baseline, Week 8, Week 16, Week 32 and Week 52
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (AP)
Time frame: Baseline, Week 8, Week 16, Week 32 and Week 52
Change From Baseline in Bilirubin and Direct Bilirubin
Time frame: Baseline, Week 8, Week 16, Week 32 and Week 52
Change From Baseline in Gamma Glutamyl Transferase
Time frame: Baseline, Week 8, Week 16, Week 32 and Week 52
Change From Baseline in Creatinine
Time frame: Baseline, Week 8, Week 16, Week 32 and Week 52
Change From Baseline in Urea Nitrogen
Time frame: Baseline, Week 8, Week 16, Week 32 and Week 52
Change From Baseline in Urate
Time frame: Baseline, Week 8, Week 16, Week 32 and Week 52
Change From Baseline in Glucose, Cholesterol, Triglycerides, Sodium, Potassium, Chloride and Calcium
Time frame: Baseline, Week 8, Week 16, Week 32 and Week 52
Change From Baseline in Albumin and Protein
Time frame: Baseline, Week 8, Week 16, Week 32 and Week 52
Change From Baseline in Alpha Fetoprotein
Time frame: Baseline, Week 8, Week 16, Week 32 and Week 52
Change From Baseline in Cystatin C
Time frame: Baseline, Week 8, Week 16, Week 32 and Week 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
32 sites in 12 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 Congenital Heart Disease, run by Actelion at 32 sites in 12 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 4 inclusion and 5 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 30 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 32 sites in United States, Australia, China, Poland, France and 7 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 13 Sep 2022). 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 in Peak Oxygen Uptake/Consumption (VO2) Up to Week 16 (time frame: Baseline up to Week 16). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Mar 2025.