Trial Outcomes & Findings for A Long Term Study to Find Out if Macitentan is an Effective and Safe Treatment for Patients With Heart Failure With Preserved Ejection Fraction and Pulmonary Vascular Disease (NCT NCT03714815)

Last Updated: 2025-02-04

Results Overview

Number of participants with all-cause deaths up to 30 days after study treatment discontinuation were reported. All-cause deaths are defined as all anticipated and unanticipated deaths due to any cause.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

91 participants

Primary outcome timeframe

Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks)

Results posted on

2025-02-04

Participant Flow

Participant milestones

Participant milestones
Measure	Macitentan 10 mg Eligible participants who remained in the main study (NCT03153111) for at least 24 weeks after randomization, entered this open-label extension study to receive macitentan 10 milligrams (mg) tablet orally once daily until the end of the treatment (treatment exposure ranged from 0.4 to 126 weeks).
Overall Study STARTED	91
Overall Study COMPLETED	76
Overall Study NOT COMPLETED	15

Reasons for withdrawal

Reasons for withdrawal
Measure	Macitentan 10 mg Eligible participants who remained in the main study (NCT03153111) for at least 24 weeks after randomization, entered this open-label extension study to receive macitentan 10 milligrams (mg) tablet orally once daily until the end of the treatment (treatment exposure ranged from 0.4 to 126 weeks).
Overall Study Physician Decision	2
Overall Study Withdrawal by Subject	2
Overall Study Death	11

Baseline Characteristics

A Long Term Study to Find Out if Macitentan is an Effective and Safe Treatment for Patients With Heart Failure With Preserved Ejection Fraction and Pulmonary Vascular Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Macitentan 10 mg n=91 Participants Eligible participants who remained in the main study (NCT03153111) for at least 24 weeks after randomization, entered this open-label extension study to receive macitentan 10 milligrams (mg) tablet orally once daily until the end of the treatment (treatment exposure ranged from 0.4 to 126 weeks).
Age, Continuous	72.7 years STANDARD_DEVIATION 9.21 • n=5 Participants
Age, Customized From 18 to 64 years	14 Participants n=5 Participants
Age, Customized From 65 to 84 years	69 Participants n=5 Participants
Age, Customized 85 years and over	8 Participants n=5 Participants
Sex: Female, Male Female	59 Participants n=5 Participants
Sex: Female, Male Male	32 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	86 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race/Ethnicity, Customized White	87 Participants n=5 Participants
Race/Ethnicity, Customized More than one race	0 Participants n=5 Participants
Race/Ethnicity, Customized Unknown or Not Reported	0 Participants n=5 Participants
Race/Ethnicity, Customized Other	2 Participants n=5 Participants
Region of Enrollment ARGENTINA	1 Participants n=5 Participants
Region of Enrollment AUSTRIA	2 Participants n=5 Participants
Region of Enrollment BRAZIL	2 Participants n=5 Participants
Region of Enrollment BULGARIA	8 Participants n=5 Participants
Region of Enrollment DENMARK	2 Participants n=5 Participants
Region of Enrollment FRANCE	5 Participants n=5 Participants
Region of Enrollment GERMANY	4 Participants n=5 Participants
Region of Enrollment ISRAEL	23 Participants n=5 Participants
Region of Enrollment POLAND	7 Participants n=5 Participants
Region of Enrollment ROMANIA	4 Participants n=5 Participants
Region of Enrollment RUSSIAN FEDERATION	14 Participants n=5 Participants
Region of Enrollment SWEDEN	2 Participants n=5 Participants
Region of Enrollment UNITED KINGDOM	3 Participants n=5 Participants
Region of Enrollment UNITED STATES	14 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks)

Population: The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).

Outcome measures

Outcome measures
Measure	Macitentan 10 mg n=91 Participants Eligible participants who remained in the main study (NCT03153111) for at least 24 weeks after randomization, entered this open-label extension study to receive macitentan 10 milligrams (mg) tablet orally once daily until the end of the treatment (treatment exposure ranged from 0.4 to 126 weeks).
Number of Participants With All-cause Deaths up to 30 Days After Study Treatment Discontinuation	11 Participants

PRIMARY outcome

Timeframe: Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks)

Population: The safety analysis set included all participants who received at least 1 dose of macitentan 10 mg.

Number of participants with all-cause hospital admissions up to 30 days after study treatment discontinuation were reported.

Outcome measures

Outcome measures
Measure	Macitentan 10 mg n=91 Participants Eligible participants who remained in the main study (NCT03153111) for at least 24 weeks after randomization, entered this open-label extension study to receive macitentan 10 milligrams (mg) tablet orally once daily until the end of the treatment (treatment exposure ranged from 0.4 to 126 weeks).
Number of Participants With All-cause Hospital Admissions up to 30 Days After Study Treatment Discontinuation	42 Participants

PRIMARY outcome

Timeframe: Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks)

Population: The safety analysis set included all participants who received at least 1 dose of macitentan 10 mg.

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 a suspected transmission of any infectious agent via a medicinal product, 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. Any AE and SAE occurring at or after the study treatment start up to 30 days after end of treatment (EOT) within the analysis set was considered to be treatment-emergent.

Outcome measures

Outcome measures
Measure	Macitentan 10 mg n=91 Participants Eligible participants who remained in the main study (NCT03153111) for at least 24 weeks after randomization, entered this open-label extension study to receive macitentan 10 milligrams (mg) tablet orally once daily until the end of the treatment (treatment exposure ranged from 0.4 to 126 weeks).
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) up to 30 Days After Study Treatment Discontinuation TEAEs	81 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) up to 30 Days After Study Treatment Discontinuation TESAEs	49 Participants

PRIMARY outcome

Timeframe: Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks)

Population: The safety analysis set included all participants who received at least 1 dose of macitentan 10 mg.

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 within the analysis set was considered to be treatment-emergent.

Outcome measures

Outcome measures
Measure	Macitentan 10 mg n=91 Participants Eligible participants who remained in the main study (NCT03153111) for at least 24 weeks after randomization, entered this open-label extension study to receive macitentan 10 milligrams (mg) tablet orally once daily until the end of the treatment (treatment exposure ranged from 0.4 to 126 weeks).
Number of Participants With TEAEs Leading to Premature Discontinuation of Study Treatment	25 Participants

PRIMARY outcome

Timeframe: Baseline and Week 24

Population: The safety analysis set included all participants who received at least 1 dose of macitentan 10 mg. Here, "N" (number of participants analyzed) specifies number of participants evaluable for this outcome measure.

Change from baseline in systolic and diastolic arterial BP at Week 24 was reported.

Outcome measures

Outcome measures
Measure	Macitentan 10 mg n=62 Participants Eligible participants who remained in the main study (NCT03153111) for at least 24 weeks after randomization, entered this open-label extension study to receive macitentan 10 milligrams (mg) tablet orally once daily until the end of the treatment (treatment exposure ranged from 0.4 to 126 weeks).
Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP) at Week 24 Systolic BP	-5.01 millimeters of mercury (mmHg) Standard Deviation 13.152
Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP) at Week 24 Diastolic BP	-3.34 millimeters of mercury (mmHg) Standard Deviation 9.903

PRIMARY outcome

Timeframe: Baseline and Week 52

Change from baseline in systolic and diastolic arterial BP at Week 52 was reported.

Outcome measures

Outcome measures
Measure	Macitentan 10 mg n=53 Participants Eligible participants who remained in the main study (NCT03153111) for at least 24 weeks after randomization, entered this open-label extension study to receive macitentan 10 milligrams (mg) tablet orally once daily until the end of the treatment (treatment exposure ranged from 0.4 to 126 weeks).
Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP) at Week 52 Systolic BP	-2.10 mmHg Standard Deviation 20.855
Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP) at Week 52 Diastolic BP	-0.79 mmHg Standard Deviation 11.685

PRIMARY outcome

Timeframe: Baseline and Week 24

Change from baseline in pulse rate at Week 24 was reported.

Outcome measures

Outcome measures
Measure	Macitentan 10 mg n=62 Participants Eligible participants who remained in the main study (NCT03153111) for at least 24 weeks after randomization, entered this open-label extension study to receive macitentan 10 milligrams (mg) tablet orally once daily until the end of the treatment (treatment exposure ranged from 0.4 to 126 weeks).
Change From Baseline in Pulse Rate at Week 24	0.59 beats per minute (bpm) Standard Deviation 9.706

PRIMARY outcome

Timeframe: Baseline and Week 52

Change from baseline in pulse rate at Week 52 was reported.

Outcome measures

Outcome measures
Measure	Macitentan 10 mg n=53 Participants Eligible participants who remained in the main study (NCT03153111) for at least 24 weeks after randomization, entered this open-label extension study to receive macitentan 10 milligrams (mg) tablet orally once daily until the end of the treatment (treatment exposure ranged from 0.4 to 126 weeks).
Change From Baseline in Pulse Rate at Week 52	2.62 bpm Standard Deviation 18.441

PRIMARY outcome

Timeframe: Baseline and Week 24

Change from baseline in body weight at Week 24 was reported.

Outcome measures

Outcome measures
Measure	Macitentan 10 mg n=64 Participants Eligible participants who remained in the main study (NCT03153111) for at least 24 weeks after randomization, entered this open-label extension study to receive macitentan 10 milligrams (mg) tablet orally once daily until the end of the treatment (treatment exposure ranged from 0.4 to 126 weeks).
Change From Baseline in Body Weight at Week 24	0.25 kilograms (kg) Standard Deviation 6.353

PRIMARY outcome

Timeframe: Baseline and Week 52

Change from baseline in body weight at Week 52 was reported.

Outcome measures

Outcome measures
Measure	Macitentan 10 mg n=56 Participants Eligible participants who remained in the main study (NCT03153111) for at least 24 weeks after randomization, entered this open-label extension study to receive macitentan 10 milligrams (mg) tablet orally once daily until the end of the treatment (treatment exposure ranged from 0.4 to 126 weeks).
Change From Baseline in Body Weight at Week 52	-0.16 kg Standard Deviation 8.200

PRIMARY outcome

Timeframe: Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks)

Number of participants with treatment-emergent MLAs (Hemoglobin \[grams/Liter{L}\], Hematocrit \[L/L\], Leukocytes \[10\^9cells/L\], Lymphocytes \[10\^9cells/L\], Alanine Aminotransferase \[Units/L {U/L}\], Aspartate Aminotransferase \[U/L\], Bilirubin \[micromoles/L {mcmol/L}\], Alkaline Phosphatase \[U/L\], Creatinine \[mcmol/L\], Urea Nitrogen \[mmol/L\], Urate \[mcmol/L\], Potassium \[mmol/L\], Sodium \[mmol/L\], Magnesium \[mmol/L\], Calcium \[mmol/L\] were reported. Abnormalities that occurred after study treatment start and up to 30 days after study treatment discontinuation, that were not present at baseline, were treatment-emergent. Here, \> signifies greater than; \< signifies less than; ULN signifies upper limit of normal; and L=Low, H=High, LL=low/low, HH=high/high, LLL=lower/worse than LL, HHH=higher/worse than HH.

Outcome measures

Outcome measures
Measure	Macitentan 10 mg n=85 Participants Eligible participants who remained in the main study (NCT03153111) for at least 24 weeks after randomization, entered this open-label extension study to receive macitentan 10 milligrams (mg) tablet orally once daily until the end of the treatment (treatment exposure ranged from 0.4 to 126 weeks).
Number of Participants With Treatment-emergent Marked Laboratory Abnormalities (MLAs) up to 30 Days After Study Treatment Discontinuation Hemoglobin:LL<100	10 Participants
Number of Participants With Treatment-emergent Marked Laboratory Abnormalities (MLAs) up to 30 Days After Study Treatment Discontinuation Hematocrit: LL(<0.28-females;<0.32-males)	5 Participants
Number of Participants With Treatment-emergent Marked Laboratory Abnormalities (MLAs) up to 30 Days After Study Treatment Discontinuation Leukocytes: HH (>20.0)	1 Participants
Number of Participants With Treatment-emergent Marked Laboratory Abnormalities (MLAs) up to 30 Days After Study Treatment Discontinuation Lymphocytes: LLL (<0.5)	1 Participants
Number of Participants With Treatment-emergent Marked Laboratory Abnormalities (MLAs) up to 30 Days After Study Treatment Discontinuation Lymphocytes: LL (<0.8)	10 Participants
Number of Participants With Treatment-emergent Marked Laboratory Abnormalities (MLAs) up to 30 Days After Study Treatment Discontinuation Alanine Aminotransferase: HH (>3 ULN)	1 Participants
Number of Participants With Treatment-emergent Marked Laboratory Abnormalities (MLAs) up to 30 Days After Study Treatment Discontinuation Aspartate Aminotransferase: HH (>3 ULN)	1 Participants
Number of Participants With Treatment-emergent Marked Laboratory Abnormalities (MLAs) up to 30 Days After Study Treatment Discontinuation Alkaline Phosphatase: HH (>2.5 ULN)	1 Participants
Number of Participants With Treatment-emergent Marked Laboratory Abnormalities (MLAs) up to 30 Days After Study Treatment Discontinuation Bilirubin: HH (>2 ULN)	1 Participants
Number of Participants With Treatment-emergent Marked Laboratory Abnormalities (MLAs) up to 30 Days After Study Treatment Discontinuation Bilirubin: HHH (>5 ULN)	1 Participants
Number of Participants With Treatment-emergent Marked Laboratory Abnormalities (MLAs) up to 30 Days After Study Treatment Discontinuation Creatinine: HH (>1.5 ULN)	2 Participants
Number of Participants With Treatment-emergent Marked Laboratory Abnormalities (MLAs) up to 30 Days After Study Treatment Discontinuation Urea Nitrogen: HH (>2.5 ULN)	3 Participants
Number of Participants With Treatment-emergent Marked Laboratory Abnormalities (MLAs) up to 30 Days After Study Treatment Discontinuation Urate: HH (>590)	15 Participants
Number of Participants With Treatment-emergent Marked Laboratory Abnormalities (MLAs) up to 30 Days After Study Treatment Discontinuation Urate: HHH (>720)	3 Participants
Number of Participants With Treatment-emergent Marked Laboratory Abnormalities (MLAs) up to 30 Days After Study Treatment Discontinuation Sodium: LLL (<130)	3 Participants
Number of Participants With Treatment-emergent Marked Laboratory Abnormalities (MLAs) up to 30 Days After Study Treatment Discontinuation Potassium: LLL (<3.0)	1 Participants
Number of Participants With Treatment-emergent Marked Laboratory Abnormalities (MLAs) up to 30 Days After Study Treatment Discontinuation Potassium: LL (<3.2)	5 Participants
Number of Participants With Treatment-emergent Marked Laboratory Abnormalities (MLAs) up to 30 Days After Study Treatment Discontinuation Potassium: HH (>5.5)	5 Participants
Number of Participants With Treatment-emergent Marked Laboratory Abnormalities (MLAs) up to 30 Days After Study Treatment Discontinuation Magnesium: HHH (>1.23)	1 Participants
Number of Participants With Treatment-emergent Marked Laboratory Abnormalities (MLAs) up to 30 Days After Study Treatment Discontinuation Calcium: LLL (<1.75)	1 Participants
Number of Participants With Treatment-emergent Marked Laboratory Abnormalities (MLAs) up to 30 Days After Study Treatment Discontinuation Calcium: LL (<2.0)	2 Participants

PRIMARY outcome

Timeframe: Baseline and Week 24

Change from baseline in hemoglobin at Week 24 was reported.

Outcome measures

Outcome measures
Measure	Macitentan 10 mg n=59 Participants Eligible participants who remained in the main study (NCT03153111) for at least 24 weeks after randomization, entered this open-label extension study to receive macitentan 10 milligrams (mg) tablet orally once daily until the end of the treatment (treatment exposure ranged from 0.4 to 126 weeks).
Change From Baseline in Hemoglobin at Week 24	-4.13 grams per liter (g/L) Standard Deviation 11.324

PRIMARY outcome

Timeframe: Baseline and Week 52

Change from baseline in hemoglobin at Week 52 was reported.

Outcome measures

Outcome measures
Measure	Macitentan 10 mg n=51 Participants Eligible participants who remained in the main study (NCT03153111) for at least 24 weeks after randomization, entered this open-label extension study to receive macitentan 10 milligrams (mg) tablet orally once daily until the end of the treatment (treatment exposure ranged from 0.4 to 126 weeks).
Change From Baseline in Hemoglobin at Week 52	-1.10 grams per litre (g/L) Standard Deviation 13.241

PRIMARY outcome

Timeframe: Baseline and Week 24

Change from baseline in leukocytes and platelets at Week 24 was reported.

Outcome measures

Outcome measures
Measure	Macitentan 10 mg n=59 Participants Eligible participants who remained in the main study (NCT03153111) for at least 24 weeks after randomization, entered this open-label extension study to receive macitentan 10 milligrams (mg) tablet orally once daily until the end of the treatment (treatment exposure ranged from 0.4 to 126 weeks).
Change From Baseline in Leukocytes and Platelets at Week 24 Leukocytes	-0.078 10^9 cells/L Standard Deviation 1.6871
Change From Baseline in Leukocytes and Platelets at Week 24 Platelets	1.39 10^9 cells/L Standard Deviation 36.102

PRIMARY outcome

Timeframe: Baseline and Week 52

Change from baseline in leukocytes and platelets at Week 52 was reported.

Outcome measures

Outcome measures
Measure	Macitentan 10 mg n=51 Participants Eligible participants who remained in the main study (NCT03153111) for at least 24 weeks after randomization, entered this open-label extension study to receive macitentan 10 milligrams (mg) tablet orally once daily until the end of the treatment (treatment exposure ranged from 0.4 to 126 weeks).
Change From Baseline in Leukocytes and Platelets at Week 52 Leukocytes	-0.503 10^9 cells/L Standard Deviation 1.5090
Change From Baseline in Leukocytes and Platelets at Week 52 Platelets	-9.02 10^9 cells/L Standard Deviation 37.285

PRIMARY outcome

Timeframe: Baseline and Week 24

Change from baseline in alanine aminotransferase and aspartate aminotransferase at Week 24 was reported.

Outcome measures

Outcome measures
Measure	Macitentan 10 mg n=59 Participants Eligible participants who remained in the main study (NCT03153111) for at least 24 weeks after randomization, entered this open-label extension study to receive macitentan 10 milligrams (mg) tablet orally once daily until the end of the treatment (treatment exposure ranged from 0.4 to 126 weeks).
Change From Baseline in Alanine Aminotransferase and Aspartate Aminotransferase at Week 24 Alanine Aminotransferase	-0.49 units per liter (U/L) Standard Deviation 7.590
Change From Baseline in Alanine Aminotransferase and Aspartate Aminotransferase at Week 24 Aspartate Aminotransferase	-0.2 units per liter (U/L) Standard Deviation 7.76

PRIMARY outcome

Timeframe: Baseline and Week 52

Change from baseline in alanine aminotransferase and aspartate aminotransferase at Week 52 was reported.

Outcome measures

Outcome measures
Measure	Macitentan 10 mg n=51 Participants Eligible participants who remained in the main study (NCT03153111) for at least 24 weeks after randomization, entered this open-label extension study to receive macitentan 10 milligrams (mg) tablet orally once daily until the end of the treatment (treatment exposure ranged from 0.4 to 126 weeks).
Change From Baseline in Alanine Aminotransferase and Aspartate Aminotransferase at Week 52 Alanine Aminotransferase	0.10 U/L Standard Deviation 7.529
Change From Baseline in Alanine Aminotransferase and Aspartate Aminotransferase at Week 52 Aspartate Aminotransferase	1.2 U/L Standard Deviation 6.52

PRIMARY outcome

Timeframe: Baseline and Week 24

Change from baseline in bilirubin at Week 24 was reported.

Outcome measures

Outcome measures
Measure	Macitentan 10 mg n=58 Participants Eligible participants who remained in the main study (NCT03153111) for at least 24 weeks after randomization, entered this open-label extension study to receive macitentan 10 milligrams (mg) tablet orally once daily until the end of the treatment (treatment exposure ranged from 0.4 to 126 weeks).
Change From Baseline in Bilirubin at Week 24	-0.0970 micromoles per liter (mcmol/L) Standard Deviation 4.20548

PRIMARY outcome

Timeframe: Baseline and Week 52

Change from baseline in bilirubin at Week 52 was reported.

Outcome measures

Outcome measures
Measure	Macitentan 10 mg n=49 Participants Eligible participants who remained in the main study (NCT03153111) for at least 24 weeks after randomization, entered this open-label extension study to receive macitentan 10 milligrams (mg) tablet orally once daily until the end of the treatment (treatment exposure ranged from 0.4 to 126 weeks).
Change From Baseline in Bilirubin at Week 52	0.2041 mcmol/L Standard Deviation 4.65018

PRIMARY outcome

Timeframe: Baseline and Week 24

Change from baseline in eGFR rate at Week 24 was reported.

Outcome measures

Outcome measures
Measure	Macitentan 10 mg n=59 Participants Eligible participants who remained in the main study (NCT03153111) for at least 24 weeks after randomization, entered this open-label extension study to receive macitentan 10 milligrams (mg) tablet orally once daily until the end of the treatment (treatment exposure ranged from 0.4 to 126 weeks).
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 24	-4.05 milliliters/minute/1.73 meter square Standard Deviation 11.766

PRIMARY outcome

Timeframe: Baseline and Week 52

Change from baseline in eGFR rate at Week 52 was reported.

Outcome measures

Outcome measures
Measure	Macitentan 10 mg n=51 Participants Eligible participants who remained in the main study (NCT03153111) for at least 24 weeks after randomization, entered this open-label extension study to receive macitentan 10 milligrams (mg) tablet orally once daily until the end of the treatment (treatment exposure ranged from 0.4 to 126 weeks).
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 52	-1.80 milliliters/minute/1.73 meter square Standard Deviation 13.510

Adverse Events

Macitentan 10 mg

Serious events: 49 serious events

Other events: 45 other events

Deaths: 11 deaths

Serious adverse events

Serious adverse events
Measure	Macitentan 10 mg n=91 participants at risk Eligible participants who remained in the main study (NCT03153111) for at least 24 weeks after randomization, entered this open-label extension study to receive macitentan 10 milligrams (mg) tablet orally once daily until the end of the treatment (treatment exposure ranged from 0.4 to 126 weeks).
Blood and lymphatic system disorders Anaemia	2.2% 2/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Cardiac disorders Acute Left Ventricular Failure	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Cardiac disorders Angina Pectoris	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Cardiac disorders Atrial Fibrillation	2.2% 2/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Cardiac disorders Atrioventricular Block Complete	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Cardiac disorders Bradycardia	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Cardiac disorders Cardiac Arrest	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Cardiac disorders Cardiac Failure Acute	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Cardiac disorders Cardiac Failure Chronic	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Cardiac disorders Cardiac Failure Congestive	6.6% 6/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Cardiac disorders Left Ventricular Failure	3.3% 3/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Cardiac disorders Right Ventricular Failure	5.5% 5/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Cardiac disorders Sinus Node Dysfunction	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Eye disorders Retinal Vein Thrombosis	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Gastrointestinal disorders Abdominal Incarcerated Hernia	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Gastrointestinal disorders Ascites	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Gastrointestinal disorders Duodenal Ulcer Haemorrhage	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Gastrointestinal disorders Gastrointestinal Haemorrhage	2.2% 2/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Gastrointestinal disorders Ileus	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
General disorders Chest Pain	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
General disorders Death	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
General disorders No Adverse Event	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
General disorders Non-Cardiac Chest Pain	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
General disorders Ulcer Haemorrhage	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Hepatobiliary disorders Cholecystitis Acute	2.2% 2/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Infections and infestations Cellulitis	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Infections and infestations Covid-19	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Infections and infestations Covid-19 Pneumonia	3.3% 3/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Infections and infestations Herpes Zoster	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Infections and infestations Pneumonia	3.3% 3/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Infections and infestations Pneumonia Viral	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Infections and infestations Sepsis	2.2% 2/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Injury, poisoning and procedural complications Limb Injury	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Injury, poisoning and procedural complications Subcutaneous Haematoma	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Injury, poisoning and procedural complications Wound Dehiscence	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Investigations Blood Potassium Increased	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Investigations International Normalised Ratio Increased	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Investigations Sars-Cov-2 Test Positive	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Metabolism and nutrition disorders Fluid Retention	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Metabolism and nutrition disorders Hyperglycaemia	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Metabolism and nutrition disorders Hyperkalaemia	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Musculoskeletal and connective tissue disorders Intervertebral Disc Protrusion	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon Cancer	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant Neoplasm of Unknown Primary Site	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to Peritoneum	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Plasma Cell Myeloma	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Small Intestine Carcinoma	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine Neoplasm	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Nervous system disorders Cerebrovascular Accident	2.2% 2/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Nervous system disorders Ischaemic Stroke	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Nervous system disorders Radiculopathy	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Renal and urinary disorders Acute Kidney Injury	5.5% 5/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Renal and urinary disorders Renal Impairment	2.2% 2/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Renal and urinary disorders Urinary Retention	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Respiratory, thoracic and mediastinal disorders Acute Respiratory Failure	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Respiratory, thoracic and mediastinal disorders Dyspnoea Exertional	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Respiratory, thoracic and mediastinal disorders Haemoptysis	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Respiratory, thoracic and mediastinal disorders Pleural Effusion	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Respiratory, thoracic and mediastinal disorders Pulmonary Hypertension	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Surgical and medical procedures Cardiac Pacemaker Replacement	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Surgical and medical procedures Cholecystectomy	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Surgical and medical procedures Small Intestinal Resection	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Surgical and medical procedures Thyroidectomy	1.1% 1/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).

Other adverse events

Other adverse events
Measure	Macitentan 10 mg n=91 participants at risk Eligible participants who remained in the main study (NCT03153111) for at least 24 weeks after randomization, entered this open-label extension study to receive macitentan 10 milligrams (mg) tablet orally once daily until the end of the treatment (treatment exposure ranged from 0.4 to 126 weeks).
Blood and lymphatic system disorders Anaemia	6.6% 6/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Cardiac disorders Right Ventricular Failure	6.6% 6/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Gastrointestinal disorders Constipation	6.6% 6/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Gastrointestinal disorders Nausea	5.5% 5/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
General disorders Oedema Peripheral	7.7% 7/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Infections and infestations Upper Respiratory Tract Infection	5.5% 5/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Infections and infestations Urinary Tract Infection	9.9% 9/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Investigations Haemoglobin Decreased	5.5% 5/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Investigations Weight Increased	5.5% 5/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Musculoskeletal and connective tissue disorders Back Pain	7.7% 7/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Musculoskeletal and connective tissue disorders Pain in Extremity	6.6% 6/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Nervous system disorders Dizziness	7.7% 7/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Respiratory, thoracic and mediastinal disorders Dyspnoea	12.1% 11/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).
Vascular disorders Hypotension	5.5% 5/91 • Up to 30 days after study treatment discontinuation (treatment exposure ranged from 0.4 to 126 weeks) The safety analysis set included all participants who received at least 1 dose of macitentan 10 milligrams (mg).

Additional Information

Clinical Scientific Leader

Actelion Pharmaceuticals Ltd

Phone: 844-434-4210

Email: [email protected]

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 30 days before submission for publication or presentation.
Publication restrictions are in place

Restriction type: OTHER