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NCT03153137: RUBATO

Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects

Completed Phase 3 Results posted Last updated 30 March 2025
What this trial tests

Phase 3 trial testing Macitentan 10 mg in Congenital Heart Disease in 142 participants. Completed in 26 July 2021.

Timeline
14 August 2017
Primary endpoint
30 June 2021
26 July 2021

Quick facts

Lead sponsorActelion
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment142
Start date14 August 2017
Primary completion30 June 2021
Estimated completion26 July 2021
Sites32 locations across Denmark, France, New Zealand, Taiwan, United Kingdom, Germany, Poland, Canada

Drugs / interventions tested

Conditions studied

Sponsor

Actelion — full company profile →

Who can join

12 and older, any sex, with Congenital Heart Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Peak Oxygen Uptake/Consumption (VO2) Up to Week 16 Primary · Baseline up to Week 16

Change from baseline in peak VO2 up to Week 16 was reported.

GroupValue95% CI
Placebo-0.67± 2.657
Macitentan-0.16± 2.855
Change From Baseline in Peak VO2 Up to Week 52 Secondary · Baseline up to Week 52

Change from baseline in peak VO2 up to Week 52 was reported.

GroupValue95% CI
Placebo-0.92± 0.296
Macitentan-0.31± 0.293
Change From Baseline in Mean Count Per Minute of Daily Physical Activity Measured by Accelerometer (PA-Ac) Up to Week 16 Secondary · Baseline 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).

GroupValue95% CI
Placebo-14.34± 117.562
Macitentan-3.02± 92.443
Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) Secondary · Up to 56 weeks

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.

GroupValue95% CI
Placebo9
Macitentan13
Number of Participants With Treatment-emergent Adverse Events (AEs) Secondary · Up to 56 weeks

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.

GroupValue95% CI
Placebo44
Macitentan48
Number of Participants With AEs Leading to Premature Discontinuation of Study Treatment Secondary · Up to 56 weeks

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.

GroupValue95% CI
Placebo1
Macitentan3
Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP) Secondary · Baseline, Week 8, Week 16, Week 32 and Week 52

Change from baseline in systolic and diastolic arterial BP at Week 8, Week 16, Week 32 and Week 52 was reported.

Baseline
GroupValue95% CI
Placebo116.0± 12.10
Macitentan117.0± 10.95
Systolic BP: Week 8
GroupValue95% CI
Placebo2.5± 14.41
Macitentan-0.4± 11.67
Systolic BP: Week 16
GroupValue95% CI
Placebo0.5± 14.68
Macitentan-4.6± 13.05
Systolic BP: Week 32
GroupValue95% CI
Placebo-6.3± 15.09
Macitentan-3.1± 10.51
Systolic BP: Week 52
GroupValue95% CI
Placebo0.0± 12.12
Macitentan-4.8± 12.08
Diastolic BP: Week 8
GroupValue95% CI
Placebo-0.2± 5.86
Macitentan-0.1± 9.57
Diastolic BP: Week 16
GroupValue95% CI
Placebo-0.6± 10.06
Macitentan-3.1± 8.74
Diastolic BP: Week 32
GroupValue95% CI
Placebo1.3± 8.64
Macitentan-1.4± 8.21
Change From Baseline in Pulse Rate Secondary · Baseline, Week 8, Week 16, Week 32 and Week 52

Change from baseline in pulse rate at Week 8, Week 16, Week 32 and Week 52 was reported.

Baseline
GroupValue95% CI
Placebo81.3± 12.52
Macitentan78.2± 13.33
Week 8
GroupValue95% CI
Placebo-3.9± 12.80
Macitentan-5.9± 12.07
Week 16
GroupValue95% CI
Placebo0.1± 14.76
Macitentan-0.1± 11.57
Week 32
GroupValue95% CI
Placebo0.2± 12.37
Macitentan1.1± 9.10
Week 52
GroupValue95% CI
Placebo-0.7± 11.56
Macitentan-2.9± 10.25
Change From Baseline in Oxygen Saturation (SpO2) Secondary · Baseline, Week 8, Week 16, Week 32 and Week 52

Change from baseline in SpO2 was reported.

Baseline
GroupValue95% CI
Placebo92.6± 3.22
Macitentan92.8± 2.84
Week 8
GroupValue95% CI
Placebo0.0± 3.20
Macitentan1.2± 2.78
Week 16
GroupValue95% CI
Placebo0.5± 2.57
Macitentan0.8± 2.75
Week 32
GroupValue95% CI
Placebo0.8± 2.94
Macitentan1.4± 3.73
Week 52
GroupValue95% CI
Placebo1.4± 2.77
Macitentan0.9± 2.99
Change From Baseline in Body Weight Secondary · Baseline, Week 8, Week 16, Week 32 and Week 52

Change from baseline in body weight was reported.

Baseline
GroupValue95% CI
Placebo68.89± 17.296
Macitentan67.38± 14.721
Week 8
GroupValue95% CI
Placebo-0.38± 1.996
Macitentan0.43± 1.568
Week 16
GroupValue95% CI
Placebo0.21± 2.028
Macitentan0.58± 2.230
Week 32
GroupValue95% CI
Placebo0.73± 2.952
Macitentan0.77± 3.411
Week 52
GroupValue95% CI
Placebo1.44± 3.746
Macitentan1.30± 4.358
Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Values Secondary · Up to 56 weeks

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 be

Platelets: LL (< 75)
GroupValue95% CI
Placebo2
Macitentan1
Lymphocytes: HH (> 4.0)
GroupValue95% CI
Placebo0
Macitentan1
Neutrophils: LL (< 1.5)
GroupValue95% CI
Placebo0
Macitentan2
Prothrombin International Normalized Ratio: HH (>= 1.5 ULN)
GroupValue95% CI
Placebo3
Macitentan5
Prothrombin International Normalized Ratio: HH (>= 2.5 ULN)
GroupValue95% CI
Placebo1
Macitentan1
Bilirubin: HH (>= 2 ULN)
GroupValue95% CI
Placebo1
Macitentan2
Alkaline Phosphatase: HH (> 2.5 ULN)
GroupValue95% CI
Placebo1
Macitentan0
Glomerular Filtration Rate: LL (< 60)
GroupValue95% CI
Placebo1
Macitentan1
Change From Baseline in Hemoglobin Secondary · Baseline, Week 8, Week 16, Week 32 and Week 52

Change from baseline in hemoglobin was reported.

Baseline
GroupValue95% CI
Placebo160.4± 13.43
Macitentan159.5± 12.83
Week 8
GroupValue95% CI
Placebo0.0± 6.59
Macitentan-8.7± 9.33
Week 16
GroupValue95% CI
Placebo0.0± 7.75
Macitentan-8.7± 8.51
Week 32
GroupValue95% CI
Placebo1.3± 8.29
Macitentan-7.3± 9.84
Week 52
GroupValue95% CI
Placebo-2.9± 10.04
Macitentan-7.1± 10.02

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 56 weeks. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo
Serious: 9/69 (13%)
Deaths: 0/69
Macitentan
Serious: 13/68 (19%)
Deaths: 0/68

Serious adverse events (33 terms)

ReactionSystemPlaceboMacitentan
Arrhythmia SupraventricularCardiac disorders——
Atrial FlutterCardiac disorders——
Atrial TachycardiaCardiac disorders——
Cardiac ArrestCardiac disorders——
PalpitationsCardiac disorders——
Supraventricular TachycardiaCardiac disorders——
HyperthyroidismEndocrine disorders——
Abdominal PainGastrointestinal disorders——
Non-Cardiac Chest PainGeneral disorders——
CholelithiasisHepatobiliary disorders——
Congestive HepatopathyHepatobiliary disorders——
Abscess LimbInfections and infestations——
AppendicitisInfections and infestations——
BronchitisInfections and infestations——
CellulitisInfections and infestations——
Epstein-Barr Virus InfectionInfections and infestations——
Viral TonsillitisInfections and infestations——
Back InjuryInjury, poisoning and procedural complications——
Clavicle FractureInjury, poisoning and procedural complications——
Head InjuryInjury, poisoning and procedural complications——
Road Traffic AccidentInjury, poisoning and procedural complications——
Alanine Aminotransferase IncreasedInvestigations——
Aspartate Aminotransferase IncreasedInvestigations——
Heart Rate IncreasedInvestigations——
International Normalised Ratio IncreasedInvestigations——
Other adverse events (5 terms — click to expand)

ReactionSystemPlaceboMacitentan
HeadacheNervous system disorders——
Abdominal PainGastrointestinal disorders——
PyrexiaGeneral disorders——
NasopharyngitisInfections and infestations——
Upper Respiratory Tract InfectionInfections and infestations——

Most-reported serious reactions: Arrhythmia Supraventricular, Atrial Flutter, Atrial Tachycardia, Cardiac Arrest, Palpitations, Supraventricular Tachycardia, Hyperthyroidism, Abdominal Pain.

Data from ClinicalTrials.gov NCT03153137 adverse events section.

Sponsor's own description

The primary objective is to assess the effect of macitentan 10 mg as compared to placebo on exercise capacity through cardiopulmonary exercise testing.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

  1. The molecular mechanisms of cardiac development and related diseases.
    Li Y, Du J, Deng S, Liu B, et al · · 2024 · cited 53× · PMID 39715759 · DOI 10.1038/s41392-024-02069-8
  2. Treatment of pulmonary arterial hypertension with the dual endothelin receptor antagonist macitentan: clinical evidence and experience.
    Belge C, Delcroix M. · · 2019 · cited 16× · PMID 30736726 · DOI 10.1177/1753466618823440
  3. Efficacy of phosphodiesterase type 5 inhibitors in univentricular congenital heart disease: the SV-INHIBITION study design.
    Amedro P, Gavotto A, Abassi H, Picot MC, et al · · 2020 · cited 10× · PMID 32147955 · DOI 10.1002/ehf2.12630
  4. Pulmonary vasodilator therapy as treatment for patients with a Fontan circulation: the Emperor's new clothes?
    Ridderbos FS, Hagdorn QAJ, Berger RMF. · · 2018 · cited 6× · PMID 30338725 · DOI 10.1177/2045894018811148
  5. Cardiac Drugs in ACHD Cardiovascular Medicine.
    Ladouceur M, Valdeolmillos E, Karsenty C, Hascoet S, et al · · 2023 · cited 4× · PMID 37233157 · DOI 10.3390/jcdd10050190
  6. Impact of COVID-19 disease on clinical research in pediatric and congenital cardiology.
    Pommier V, Abassi H, Lavastre K, Calderon J, et al · · 2022 · cited 3× · PMID 35523633 · DOI 10.1016/j.arcped.2022.03.004
  7. Focused Update on Pulmonary Hypertension in Children-Selected Topics of Interest for the Adult Cardiologist.
    Albinni S, Marx M, Lang IM. · · 2020 · PMID 32825190 · DOI 10.3390/medicina56090420

Verify or expand the search:

Other trials of Macitentan 10 mg

Trials testing the same drug.

Other recruiting trials for Congenital Heart Disease

Currently open trials in the same condition.

Other Actelion trials

Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03153137.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing