NCT03775421 (RUBATO OL) is a Phase 3 clinical trial of macitentan 10 mg in Congenital Heart Disease With Fontan Circulation, sponsored by Actelion.

Who is sponsoring NCT03775421?

NCT03775421 is sponsored by Actelion.

What drugs are being tested in NCT03775421?

Interventions in NCT03775421: macitentan 10 mg.

What condition does NCT03775421 study?

NCT03775421 studies Congenital Heart Disease With Fontan Circulation.

Is NCT03775421 still recruiting?

NCT03775421 is currently terminated. Last updated 7 March 2023.

Are results published for NCT03775421?

Yes — primary outcome results have been posted to ClinicalTrials.gov. See the outcomes section above for details.

Last reviewed 2023-03-07 · How we verify

NCT03775421: RUBATO OL

Name: Drug Landscape Pharmaceutical Database
Creator: Drug Landscape
Published: 2026-01-01
License: https://creativecommons.org/licenses/by/4.0/

An Upcoming Clinical Study to Measure the Safety and Impact of a Drug Called Macitentan in Teenage and Adult Fontan Patients.

Terminated Phase 3 Results posted Last updated 7 March 2023

What this trial tests

Phase 3 trial testing macitentan 10 mg in Congenital Heart Disease With Fontan Circulation in 112 participants. Terminated before completion.

Timeline

11 April 2019

Primary endpoint
18 January 2022

18 January 2022

Quick facts

Lead sponsor	Actelion
Phase	Phase 3
Status	Terminated
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	112
Start date	11 April 2019
Primary completion	18 January 2022
Estimated completion	18 January 2022
Sites	19 locations across Denmark, France, New Zealand, Taiwan, United Kingdom, Poland, Canada, Australia

Drugs / interventions tested

macitentan 10 mg — full drug profile →

Conditions studied

Congenital Heart Disease With Fontan Circulation — all drugs for Congenital Heart Disease With Fontan Circulation →

Sponsor

Actelion — full company profile →

Who can join

12 and older, any sex, with Congenital Heart Disease With Fontan Circulation. 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.

Number of Participants With Treatment-emergent Adverse Events (TEAEs) Primary · Up to 133 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. Any AE occurring at or after the study treatment start up to 30 days after end of treatment (EOT) (limits included) within the analysis set was considered to be treatment-emergent.

Group	Value	95% CI
Macitentan 10 mg	68

Number of Participants With Treatment-emergent Serious AEs (TESAEs) Primary · Up to 133 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. 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 abo

Group	Value	95% CI
Macitentan 10 mg	18

Number of Participants With TEAEs Leading to Death Primary · Up to 133 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. Any AE occurring at or after the study treatment start up to 30 days after EOT (limits included) within the analysis set was considered to be treatment-emergent.

Group	Value	95% CI
Macitentan 10 mg	1

Number of Participants With TEAEs Leading to Premature Discontinuation of Study Treatment Primary · Up to 133 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. Any AE occurring at or after the study treatment start up to 30 days after EOT (limits included) within the analysis set was considered to be treatment-emergent.

Group	Value	95% CI
Macitentan 10 mg	2

Number of Participants With Treatment-emergent Marked Laboratory Abnormalities up to 30 Days After Study Treatment Discontinuation Primary · Up to 133 weeks

Number of participants with treatment-emergent marked laboratory abnormalities (Hemoglobin \[gram/Liter {g/L}\], Platelets \[giga/L {10\^9 cells/L}\], Leukocytes \[10\^9 cells/L\], Lymphocytes \[10\^9 cells/L\], Neutrophils \[10\^9 cells/L\], Prothrombin International Normalized Ratio \[PINR;Ratio\], Aspartate Aminotransferase \[Units/L {U/L}\], Bilirubin \[micromoles/L {mcmol/L}\], Alkaline Phosphatase \[U/L\], Glomerular Filtration Rate \[milliliter/minute/1.73 meter square\], Glucose \[millimoles/L {mmol/L}\], Potassium \[mmol/L\], Sodium \[mmol/L\], Triglycerides \[mmol/L\] were reported.

Hemoglobin: LL<100

Group	Value	95% CI
Macitentan 10 mg	1

Platelets: LL (< 75)

Group	Value	95% CI
Macitentan 10 mg	3

Leukocytes: LLL (< 1.9)

Group	Value	95% CI
Macitentan 10 mg	2

Leukocytes: LL (< 3.0)

Group	Value	95% CI
Macitentan 10 mg	10

Lymphocytes: HH (> 4.0)

Group	Value	95% CI
Macitentan 10 mg	1

Neutrophils: LL (< 1.5)

Group	Value	95% CI
Macitentan 10 mg	3

PINR: HH (>=1.5 ULN)

Group	Value	95% CI
Macitentan 10 mg	4

PINR: HHH (>= 2.5 ULN)

Group	Value	95% CI
Macitentan 10 mg	1

Change From Baseline in Hemoglobin Over Time Primary · Baseline up to Week 130

Change from baseline in hemoglobin over time was reported in this outcome measure.

Week 26

Group	Value	95% CI
Macitentan 10 mg	-6.0	± 9.94

Week 52

Group	Value	95% CI
Macitentan 10 mg	-4.0	± 9.19

Week 78

Group	Value	95% CI
Macitentan 10 mg	-5.0	± 7.20

Week 104

Group	Value	95% CI
Macitentan 10 mg	-2.4	± 10.66

Week 130

Group	Value	95% CI
Macitentan 10 mg	5.7	± 19.35

Change From Baseline in Hematocrit Over Time Primary · Baseline up to Week 130

Change from baseline in hematocrit over time was reported in this outcome measure.

Week 26

Group	Value	95% CI
Macitentan 10 mg	-0.016	± 0.0323

Week 52

Group	Value	95% CI
Macitentan 10 mg	-0.007	± 0.0288

Week 78

Group	Value	95% CI
Macitentan 10 mg	-0.011	± 0.0247

Week 104

Group	Value	95% CI
Macitentan 10 mg	-0.008	± 0.0285

Week 130

Group	Value	95% CI
Macitentan 10 mg	0.010	± 0.0624

Change From Baseline in Leukocytes, Neutrophils, Lymphocytes, and Platelets Over Time Primary · Baseline up to Week 130

Change from baseline in leukocytes, neutrophils, lymphocytes, and platelets over time were reported in this outcome measure.

Leukocytes: Week 26

Group	Value	95% CI
Macitentan 10 mg	-0.358	± 1.2966

Leukocytes: Week 52

Group	Value	95% CI
Macitentan 10 mg	-0.222	± 1.3677

Leukocytes: Week 78

Group	Value	95% CI
Macitentan 10 mg	-0.300	± 1.2868

Leukocytes: Week 104

Group	Value	95% CI
Macitentan 10 mg	-0.255	± 1.2914

Leukocytes: Week 130

Group	Value	95% CI
Macitentan 10 mg	-0.560	± 1.1186

Neutrophils: Week 26

Group	Value	95% CI
Macitentan 10 mg	-0.185	± 1.0712

Neutrophils: Week 52

Group	Value	95% CI
Macitentan 10 mg	-0.074	± 1.0624

Neutrophils: Week 78

Group	Value	95% CI
Macitentan 10 mg	-0.233	± 1.0569

Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP) Over Time Primary · Baseline up to Week 130

Change from baseline in systolic and diastolic arterial BP over time was reported in this outcome measure.

Systolic BP: Week 26

Group	Value	95% CI
Macitentan 10 mg	-0.7	± 13.00

Systolic BP: Week 52

Group	Value	95% CI
Macitentan 10 mg	-1.7	± 14.81

Systolic BP: Week 78

Group	Value	95% CI
Macitentan 10 mg	-0.7	± 14.79

Systolic BP: Week 104

Group	Value	95% CI
Macitentan 10 mg	0.7	± 6.49

Systolic BP: Week 130

Group	Value	95% CI
Macitentan 10 mg	-12	± 8.72

Diastolic BP: Week 26

Group	Value	95% CI
Macitentan 10 mg	-2.9	± 12.63

Diastolic BP: Week 52

Group	Value	95% CI
Macitentan 10 mg	-0.9	± 12.56

Diastolic BP: Week 78

Group	Value	95% CI
Macitentan 10 mg	-1.6	± 11.61

Change From Baseline in Pulse Rate Over Time Primary · Baseline up to Week 130

Change from baseline in pulse rate over time was reported in this outcome measure.

Week 26

Group	Value	95% CI
Macitentan 10 mg	-2.1	± 10.48

Week 52

Group	Value	95% CI
Macitentan 10 mg	0.9	± 10.95

Week 78

Group	Value	95% CI
Macitentan 10 mg	-1.3	± 10.12

Week 104

Group	Value	95% CI
Macitentan 10 mg	-1.7	± 8.78

Week 130

Group	Value	95% CI
Macitentan 10 mg	-0.3	± 13.05

Change From Baseline in Peripheral Oxygen Saturation (SpO2) Over Time Primary · Baseline up to Week 130

Change from baseline in SpO2 over time was reported in this outcome measure.

Week 26

Group	Value	95% CI
Macitentan 10 mg	0.2	± 3.22

Week 52

Group	Value	95% CI
Macitentan 10 mg	0.2	± 2.79

Week 78

Group	Value	95% CI
Macitentan 10 mg	-0.5	± 2.52

Week 104

Group	Value	95% CI
Macitentan 10 mg	0.3	± 2.44

Week 130

Group	Value	95% CI
Macitentan 10 mg	3.3	± 2.31

Change From Baseline in Body Weight Over Time Primary · Baseline up to Week 130

Change from baseline in body weight over time was reported in this outcome measure.

Week 26

Group	Value	95% CI
Macitentan 10 mg	0.8	± 2.89

Week 52

Group	Value	95% CI
Macitentan 10 mg	0.9	± 4.23

Week 78

Group	Value	95% CI
Macitentan 10 mg	1.7	± 3.65

Week 104

Group	Value	95% CI
Macitentan 10 mg	2.0	± 4.17

Week 130

Group	Value	95% CI
Macitentan 10 mg	2.6	± 5.54

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 133 weeks. Reporting threshold: 2%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Macitentan 10 mg

Serious: 18/111 (16%)

Deaths: 1/111

Serious adverse events (25 terms)

Reaction	System	Macitentan 10 mg
Arrhythmia	Cardiac disorders	—
Atrial Flutter	Cardiac disorders	—
Abdominal Pain	Gastrointestinal disorders	—
Colitis Ulcerative	Gastrointestinal disorders	—
Incarcerated Inguinal Hernia	Gastrointestinal disorders	—
Death	General disorders	—
Hepatic Mass	Hepatobiliary disorders	—
Covid-19	Infections and infestations	—
Cytomegalovirus Infection	Infections and infestations	—
Pneumonia	Infections and infestations	—
Anastomotic Stenosis	Injury, poisoning and procedural complications	—
Sperm Concentration Decreased	Investigations	—
Spermatozoa Progressive Motility Decreased	Investigations	—
Intervertebral Disc Protrusion	Musculoskeletal and connective tissue disorders	—
Hepatocellular Carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—
Cerebrovascular Accident	Nervous system disorders	—
Clonic Convulsion	Nervous system disorders	—
Epilepsy	Nervous system disorders	—
Abortion Spontaneous	Pregnancy, puerperium and perinatal conditions	—
Anxiety	Psychiatric disorders	—
Depression	Psychiatric disorders	—
Mental Disorder	Psychiatric disorders	—
Suicidal Ideation	Psychiatric disorders	—
Hypoxia	Respiratory, thoracic and mediastinal disorders	—
Pleurisy	Respiratory, thoracic and mediastinal disorders	—

Other adverse events (11 terms — click to expand)

Reaction	System	Macitentan 10 mg
Covid-19	Infections and infestations	—
Headache	Nervous system disorders	—
Palpitations	Cardiac disorders	—
Fatigue	General disorders	—
Anxiety	Psychiatric disorders	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—
Cough	Respiratory, thoracic and mediastinal disorders	—
Pyrexia	General disorders	—
Pharyngitis	Infections and infestations	—
Tonsillitis	Infections and infestations	—
Dizziness	Nervous system disorders	—

Most-reported serious reactions: Arrhythmia, Atrial Flutter, Abdominal Pain, Colitis Ulcerative, Incarcerated Inguinal Hernia, Death, Hepatic Mass, Covid-19.

Data from ClinicalTrials.gov NCT03775421 adverse events section.

Sponsor's own description

The aim of this open-label (OL) trial is to study the long-term use of macitentan for up to 2 years in Fontan-palliated adult and adolescent patients beyond the 52 weeks of treatment in the parent RUBATO double-blind (DB) study (AC-055H301, NCT03153137). This OL trial studies the long-term effect of macitentan in Fontan-palliated patients as it is not known if the effect of macitentan is sustained beyond 52 weeks (end of the parent RUBATO DB study). In addition, the trial also studies the long-term safety of macitentan as this is also unknown. Furthermore, the opportunity will be given to patients who were on placebo in the parent RUBATO DB study to receive macitentan 10 mg and benefit from a potentially active treatment.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

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

Verify or expand the search:

Other trials of macitentan 10 mg

Trials testing the same drug.

NCT03809650 — A Clinical Study to Find Out if Macitentan is Effective and Safe in Japanese Patients With Chronic Thromboembolic Pulmon · Phase 3 · terminated
NCT03714815 — A Long Term Study to Find Out if Macitentan is an Effective and Safe Treatment for Patients With Heart Failure With Pres · Phase 2 · terminated

Other Actelion trials

Trials by the same sponsor.

NCT05731492 — A Study of Macitentan in Children Below 2 Years of Age · Phase 1 · withdrawn
NCT05433675 — A Study of Two Macitentan Formulations in Healthy Adult Participants · Phase 1 · completed
NCT05427162 — A Study of Single and Multiple Doses of Different Formulations of a Prostacyclin Receptor Agonist · Phase 1 · completed
NCT05392530 — A Study of Two Different Test Formulations Compared to the Reference Formulation of Macitentan in Healthy Adult Particip · Phase 1 · completed
NCT05179876 — A Study Providing Treatment Access in Participants With Pulmonary Hypertension Completing a Parent Study and Having no O · Phase 3 · recruiting

Verify against primary sources

ClinicalTrials.gov — authoritative US registry record
WHO ICTRP — international registry index
EU Clinical Trials Register
Sponsor press releases (Google)

Data sources for this page

Trial protocol + status: ClinicalTrials.gov NCT03775421 (US National Library of Medicine, public domain)
Publications: Europe PMC API search by NCT ID, retrieved 10 June 2026
Drug + disease cross-links: matched in real time against Drug Landscape's normalised drug + company + condition tables
Sponsor: as reported to ClinicalTrials.gov by Actelion
Last refreshed: 7 March 2023

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/NCT03775421.

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

NCT03775421: RUBATO OL

Quick facts

Drugs / interventions tested

Conditions studied

Sponsor

Who can join

Results — posted to ClinicalTrials.gov

Adverse events — posted to ClinicalTrials.gov

Serious adverse events (25 terms)

Sponsor's own description

Publications & conference data

Related trials

Other trials of macitentan 10 mg

Other Actelion trials

Verify against primary sources