Trial Outcomes & Findings for REPAIR: Right vEntricular Remodeling in Pulmonary ArterIal hypeRtension (NCT NCT02310672)
NCT ID: NCT02310672
Last Updated: 2025-03-30
Results Overview
Change from baseline in RVSV assessed by cardiac magnetic resonance imaging (MRI) from pulmonary artery flow was reported at Week 26. Primary analysis were based on interim results as pre-planned and the primary outcome measures data table reported is finalized as is.
COMPLETED
PHASE4
89 participants
Baseline and Week 26
2025-03-30
Participant Flow
Total 112 participants were screened out of them 89 participants were enrolled in the study and of which 87 participants received study medication. Two participants who did not receive study treatment were wrongly classified as enrolled by the sites.
Participant milestones
| Measure |
Macitentan 10 mg
Participants received macitentan 10 milligrams (mg) tablets once daily until the premature discontinuation of study drug or end of treatment (EOT) on the day of the last dose of study drug at Week 52.
|
|---|---|
|
Overall Study
STARTED
|
87
|
|
Overall Study
COMPLETED
|
72
|
|
Overall Study
NOT COMPLETED
|
15
|
Reasons for withdrawal
| Measure |
Macitentan 10 mg
Participants received macitentan 10 milligrams (mg) tablets once daily until the premature discontinuation of study drug or end of treatment (EOT) on the day of the last dose of study drug at Week 52.
|
|---|---|
|
Overall Study
Death
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
|
Overall Study
Sponsor's decision
|
12
|
Baseline Characteristics
REPAIR: Right vEntricular Remodeling in Pulmonary ArterIal hypeRtension
Baseline characteristics by cohort
| Measure |
Macitentan 10 mg
n=87 Participants
Participants received macitentan 10 milligrams (mg) tablets once daily until the premature discontinuation of study drug or end of treatment (EOT) on the day of the last dose of study drug at Week 52.
|
|---|---|
|
Age, Continuous
|
45.9 years
STANDARD_DEVIATION 14.48 • n=93 Participants
|
|
Sex: Female, Male
Female
|
70 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
17 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
72 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
14 Participants
n=93 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
1 Participants
n=93 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
|
Race/Ethnicity, Customized
Asian
|
26 Participants
n=93 Participants
|
|
Race/Ethnicity, Customized
White
|
46 Participants
n=93 Participants
|
|
Race/Ethnicity, Customized
Other
|
0 Participants
n=93 Participants
|
|
Race/Ethnicity, Customized
Unknown or Not Reported
|
14 Participants
n=93 Participants
|
|
Region of Enrollment
FRANCE
|
14 Participants
n=93 Participants
|
|
Region of Enrollment
GERMANY
|
12 Participants
n=93 Participants
|
|
Region of Enrollment
ISRAEL
|
2 Participants
n=93 Participants
|
|
Region of Enrollment
ITALY
|
3 Participants
n=93 Participants
|
|
Region of Enrollment
MALAYSIA
|
8 Participants
n=93 Participants
|
|
Region of Enrollment
NETHERLANDS
|
12 Participants
n=93 Participants
|
|
Region of Enrollment
RUSSIAN FEDERATION
|
11 Participants
n=93 Participants
|
|
Region of Enrollment
SINGAPORE
|
9 Participants
n=93 Participants
|
|
Region of Enrollment
UNITED KINGDOM
|
3 Participants
n=93 Participants
|
|
Region of Enrollment
UNITED STATES
|
6 Participants
n=93 Participants
|
|
Region of Enrollment
Hong Kong
|
7 Participants
n=93 Participants
|
PRIMARY outcome
Timeframe: Baseline and Week 26Population: The Modified full analysis set (mFAS) included of all screened participants who received at least one dose of study drug and who had a baseline as well as a post-baseline measurement taken between 16 weeks and 30 weeks of treatment.
Change from baseline in RVSV assessed by cardiac magnetic resonance imaging (MRI) from pulmonary artery flow was reported at Week 26. Primary analysis were based on interim results as pre-planned and the primary outcome measures data table reported is finalized as is.
Outcome measures
| Measure |
Macitanten 10 mg
n=42 Participants
Participants received macitentan 10 milligrams (mg) tablets once daily until the premature discontinuation of study drug or end of treatment (EOT) on the day of the last dose of study drug at Week 52.
|
|---|---|
|
Change From Baseline in Right Ventricular Stroke Volume (RVSV) to Week 26
|
15.17 milliliters (mL)
Standard Error 2.75
|
PRIMARY outcome
Timeframe: Baseline and Week 26Population: mFAS included of all screened participants who received at least one dose of study drug and who had a baseline as well as a post-baseline measurement taken between 16 weeks and 30 weeks of treatment.
Ratio of Week 26 to baseline PVR as assessed by RHC was reported. PVR represents the resistance against which the right ventricle needs to pump. PVR is determined by right heart catheterization (RHC). PVR was calculated as 80\*(Mean pulmonary arterial pressure \[mPAP\] -\[Pulmonary capillary wedge pressure {PCWP} or Left ventricular end diastolic pressure {LVEDP} if PCWP not available/cardiac output \[CO\]). Primary analysis were based on interim results as pre-planned and the primary outcome measures data table reported is finalized as is.
Outcome measures
| Measure |
Macitanten 10 mg
n=42 Participants
Participants received macitentan 10 milligrams (mg) tablets once daily until the premature discontinuation of study drug or end of treatment (EOT) on the day of the last dose of study drug at Week 52.
|
|---|---|
|
Ratio of Week 26 to Baseline Pulmonary Vascular Resistance (PVR)
|
0.63 Ratio
Geometric Coefficient of Variation 0.11
|
SECONDARY outcome
Timeframe: Baseline to Week 26Population: Safety set included all screened participants who received at least one dose of study drug. Here 'N' (number of participants analyzed) signifies the number of participants evaluable for this outcome measure.
Change from baseline to Week 26 in RVEDV assessed by cardiac MRI was reported.
Outcome measures
| Measure |
Macitanten 10 mg
n=78 Participants
Participants received macitentan 10 milligrams (mg) tablets once daily until the premature discontinuation of study drug or end of treatment (EOT) on the day of the last dose of study drug at Week 52.
|
|---|---|
|
Change From Baseline in Right Ventricular End Diastolic Volume (RVEDV) to Week 26
|
-6.22 mL
Interval -12.5 to 0.07
|
SECONDARY outcome
Timeframe: Baseline to Week 26Population: Safety set included all screened participants who received at least one dose of study drug. Here 'N' (number of participants analyzed) signifies the number of participants evaluable for this outcome measure.
Change from baseline to Week 26 in RVESV assessed by cardiac MRI was reported.
Outcome measures
| Measure |
Macitanten 10 mg
n=78 Participants
Participants received macitentan 10 milligrams (mg) tablets once daily until the premature discontinuation of study drug or end of treatment (EOT) on the day of the last dose of study drug at Week 52.
|
|---|---|
|
Change From Baseline in Right Ventricular End Systolic Volume (RVESV) to Week 26
|
-16.39 mL
Interval -20.56 to -12.21
|
SECONDARY outcome
Timeframe: Baseline to Week 26Population: Safety set included all screened participants who received at least one dose of study drug. Here 'N' (number of participants analyzed) signifies the number of participants evaluable for this outcome measure.
Change from baseline to Week 26 in RVEF based on pulmonary artery flow assessed by cardiac MRI was reported.
Outcome measures
| Measure |
Macitanten 10 mg
n=72 Participants
Participants received macitentan 10 milligrams (mg) tablets once daily until the premature discontinuation of study drug or end of treatment (EOT) on the day of the last dose of study drug at Week 52.
|
|---|---|
|
Change From Baseline in Right Ventricular Ejection Fraction (RVEF) to Week 26 (% Blood Volume)
|
10.14 Percentage of blood volume
Interval 7.46 to 12.83
|
SECONDARY outcome
Timeframe: Baseline to Week 26Population: Safety set included all screened participants who received at least one dose of study drug. Here 'N' (number of participants analyzed) signifies the number of participants evaluable for this outcome measure.
Change from baseline to Week 26 in RV mass assessed by cardiac MRI was reported.
Outcome measures
| Measure |
Macitanten 10 mg
n=78 Participants
Participants received macitentan 10 milligrams (mg) tablets once daily until the premature discontinuation of study drug or end of treatment (EOT) on the day of the last dose of study drug at Week 52.
|
|---|---|
|
Change From Baseline in Right Ventricle (RV) Mass to Week 26
|
-10.10 Grams
Interval -13.81 to -6.39
|
SECONDARY outcome
Timeframe: Baseline to Week 26Population: Safety set included all screened participants who received at least one dose of study drug. Here 'N' (number of participants analyzed) signifies the number of participants evaluable for this outcome measure.
6MWD is a non-encouraged test performed in a 30 meter (m) long flat corridor, where the participant is instructed to walk as far as possible, back and forth around two cones, with the permission to slow down, rest, or stop if needed. This test is used to assess exercise capacity. The test was performed about 30 minutes after study drug administration. Any increase in the walk distance was considered improvement from baseline.
Outcome measures
| Measure |
Macitanten 10 mg
n=83 Participants
Participants received macitentan 10 milligrams (mg) tablets once daily until the premature discontinuation of study drug or end of treatment (EOT) on the day of the last dose of study drug at Week 52.
|
|---|---|
|
Change From Baseline in Six-minutes Walk Distance (6MWD) to Week 26
|
38.85 Meters
Standard Error 7.37
|
SECONDARY outcome
Timeframe: Baseline to Week 26Population: Safety Set included all screened participants who received at least one dose of study drug.
WHO FC is a classification which reflects disease severity based on symptoms. WHO Functional Classification of pulmonary hypertension comprises of Class I (participants with pulmonary hypertension but without resulting limitation of physical activity), II (participants with pulmonary hypertension resulting in slight limitation of physical activity), III (participants with pulmonary hypertension resulting in marked limitation of physical activity) and IV (participants with pulmonary hypertension with inability to carry out any physical activity without symptoms). Changes from baseline to Week 26 included: improvement (change from a higher to a lower FC), worsening (change from a lower to a higher FC) or unchanged/stable (same FC at baseline and at the post-baseline time point).
Outcome measures
| Measure |
Macitanten 10 mg
n=87 Participants
Participants received macitentan 10 milligrams (mg) tablets once daily until the premature discontinuation of study drug or end of treatment (EOT) on the day of the last dose of study drug at Week 52.
|
|---|---|
|
Change From Baseline in World Health Organization Functional Class (WHO FC) to Week 26
Missing WHO FC
|
5 Participants
|
|
Change From Baseline in World Health Organization Functional Class (WHO FC) to Week 26
Worsened WHO FC
|
1 Participants
|
|
Change From Baseline in World Health Organization Functional Class (WHO FC) to Week 26
Unchanged WHO FC
|
35 Participants
|
|
Change From Baseline in World Health Organization Functional Class (WHO FC) to Week 26
Improved WHO FC
|
46 Participants
|
Adverse Events
Macitentan 10 mg
Serious adverse events
| Measure |
Macitentan 10 mg
n=87 participants at risk
Participants received macitentan 10 milligrams (mg) tablets once daily until the premature discontinuation of study drug or end of treatment (EOT) on the day of the last dose of study drug at Week 52.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
1.1%
1/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Blood and lymphatic system disorders
Haemolytic Anaemia
|
1.1%
1/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Blood and lymphatic system disorders
Iron Deficiency Anaemia
|
1.1%
1/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Cardiac disorders
Acute Myocardial Infarction
|
2.3%
2/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Cardiac disorders
Angina Pectoris
|
1.1%
1/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Cardiac disorders
Atrial Fibrillation
|
1.1%
1/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Cardiac disorders
Cardiac Arrest
|
1.1%
1/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Cardiac disorders
Coronary Artery Disease
|
1.1%
1/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Cardiac disorders
Right Ventricular Failure
|
1.1%
1/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Cardiac disorders
Ventricular Hypokinesia
|
1.1%
1/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Rectal Haemorrhage
|
1.1%
1/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
General disorders
Therapeutic Response Decreased
|
1.1%
1/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Immune system disorders
Hypersensitivity
|
1.1%
1/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Infections and infestations
Cholangitis Infective
|
1.1%
1/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Infections and infestations
Cytomegalovirus Infection
|
1.1%
1/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Infections and infestations
Escherichia Bacteraemia
|
1.1%
1/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Infections and infestations
Herpes Zoster
|
1.1%
1/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Infections and infestations
Pneumonia
|
3.4%
3/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Infections and infestations
Sepsis
|
2.3%
2/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Infections and infestations
Urinary Tract Infection
|
1.1%
1/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
1.1%
1/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Rheumatoid Arthritis
|
1.1%
1/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Systemic Lupus Erythematosus
|
1.1%
1/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic Carcinoma
|
1.1%
1/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Nervous system disorders
Syncope
|
1.1%
1/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Renal and urinary disorders
Acute Kidney Injury
|
1.1%
1/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Reproductive system and breast disorders
Dysfunctional Uterine Bleeding
|
1.1%
1/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Reproductive system and breast disorders
Dysmenorrhoea
|
1.1%
1/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Reproductive system and breast disorders
Menorrhagia
|
1.1%
1/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Reproductive system and breast disorders
Pelvic Haemorrhage
|
1.1%
1/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.1%
1/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
1.1%
1/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Arterial Hypertension
|
2.3%
2/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism
|
2.3%
2/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
Other adverse events
| Measure |
Macitentan 10 mg
n=87 participants at risk
Participants received macitentan 10 milligrams (mg) tablets once daily until the premature discontinuation of study drug or end of treatment (EOT) on the day of the last dose of study drug at Week 52.
|
|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
9.2%
8/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Nausea
|
6.9%
6/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
General disorders
Oedema Peripheral
|
21.8%
19/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
General disorders
Pyrexia
|
8.0%
7/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Infections and infestations
Nasopharyngitis
|
6.9%
6/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
11.5%
10/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Investigations
Haemoglobin Decreased
|
11.5%
10/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
8.0%
7/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
10.3%
9/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Pain in Extremity
|
6.9%
6/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Nervous system disorders
Dizziness
|
13.8%
12/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Nervous system disorders
Headache
|
20.7%
18/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
11.5%
10/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal Congestion
|
9.2%
8/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
|
Vascular disorders
Flushing
|
5.7%
5/87 • Up to 420 Days
Safety Set included all screened participants who received at least one dose of study drug.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.
- Publication restrictions are in place
Restriction type: OTHER