Trial Outcomes & Findings for Macitentan in Pulmonary Hypertension of Sickle Cell Disease (NCT NCT02651272)

Results Overview

The occurrence of treatment emergent AEs includes having any of the following: vaso-occlusive crises requiring hospitalization; acute congestive heart failure; hypotension (defined as a mean arterial pressure less than 60mmHg); decrease in hemoglobin concentration by greater than 1 g/dL.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

4 participants

Primary outcome timeframe

20 weeks

Results posted on

2020-12-08

Participant Flow

Participant milestones

Participant milestones
Measure	Macitentan 10mg macitentan tablets, taken once daily (QD), by mouth (PO), for the treatment period lasting 16 weeks. macitentan: 10mg macitentan tablets
Overall Study STARTED	4
Overall Study COMPLETED	1
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Macitentan in Pulmonary Hypertension of Sickle Cell Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Macitentan n=4 Participants 10mg macitentan tablets, taken once daily (QD), by mouth (PO), for the treatment period lasting 16 weeks. macitentan: 10mg macitentan tablets
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: 20 weeks

The occurrence of treatment emergent AEs includes having any of the following: vaso-occlusive crises requiring hospitalization; acute congestive heart failure; hypotension (defined as a mean arterial pressure less than 60mmHg); decrease in hemoglobin concentration by greater than 1 g/dL.

Outcome measures

Outcome measures
Measure	Macitentan n=1 Participants 10mg macitentan tablets, taken once daily (QD), by mouth (PO), for the treatment period lasting 16 weeks. macitentan: 10mg macitentan tablets
Number of Participants With Treatment-emergent Adverse Events	0 Participants

SECONDARY outcome

Timeframe: Baseline, 16 weeks

RAP will be assessed by right heart catheterization. Normal range is 2-6 mmHg.

Outcome measures

Outcome measures
Measure	Macitentan n=1 Participants 10mg macitentan tablets, taken once daily (QD), by mouth (PO), for the treatment period lasting 16 weeks. macitentan: 10mg macitentan tablets
Change in Right Arterial Pressure (RAP)	-5 mmHg

SECONDARY outcome

Timeframe: Baseline, 16 weeks

RVSP will be assessed by right heart catheterization. Normal range is 15-25 mmHg.

Outcome measures

Outcome measures
Measure	Macitentan n=1 Participants 10mg macitentan tablets, taken once daily (QD), by mouth (PO), for the treatment period lasting 16 weeks. macitentan: 10mg macitentan tablets
Change in Systolic Right Ventricular Pressure (RVSP)	3 mmHg

SECONDARY outcome

Timeframe: Baseline, 16 weeks

PADP will be assessed by right heart catheterization. Normal range is 8-15 mmHg.

Outcome measures

Outcome measures
Measure	Macitentan n=1 Participants 10mg macitentan tablets, taken once daily (QD), by mouth (PO), for the treatment period lasting 16 weeks. macitentan: 10mg macitentan tablets
Change in Diastolic Pulmonary Artery Pressure (PADP)	-5 mmHg

SECONDARY outcome

Timeframe: Baseline, 16 weeks

SPAP will be assessed by right heart catheterization. Normal range is 15-25 mm Hg.

Outcome measures

Outcome measures
Measure	Macitentan n=1 Participants 10mg macitentan tablets, taken once daily (QD), by mouth (PO), for the treatment period lasting 16 weeks. macitentan: 10mg macitentan tablets
Change in Systolic Pulmonary Artery Pressure (SPAP)	7 mmHg

SECONDARY outcome

Timeframe: Baseline, Week 16

Systemic vascular resistance (SVR) will be assessed with this formula Systemic Vascular Resistance (SVR) = 80x(Mean Arterial Pressure - Mean Venous Pressure or CVP) / Cardiac Output. Normal range is 800 - 1200 dynes-sec/cm-5.

Outcome measures

Outcome measures
Measure	Macitentan n=1 Participants 10mg macitentan tablets, taken once daily (QD), by mouth (PO), for the treatment period lasting 16 weeks. macitentan: 10mg macitentan tablets
Change in Systemic Vascular Resistance Index (SVR)	-528 dynes-sec/cm-5.

SECONDARY outcome

Timeframe: Baseline to Week 16

Cardiac index (CI) will be measured in L/min/m\^2. The normal range for CI is 2.5 to 4 L/min/m\^2.

Outcome measures

Outcome measures
Measure	Macitentan n=1 Participants 10mg macitentan tablets, taken once daily (QD), by mouth (PO), for the treatment period lasting 16 weeks. macitentan: 10mg macitentan tablets
Change in Cardiac Index (CI)	.23 L/min/m^2

SECONDARY outcome

Timeframe: Baseline, 16 weeks

The 6 minute walk test (6MWT) assesses distance walked over 6 minutes (6MWD) as a sub-maximal test of aerobic capacity/endurance. Participants will walk at their normal pace for 6 minutes.

Outcome measures

Outcome measures
Measure	Macitentan n=1 Participants 10mg macitentan tablets, taken once daily (QD), by mouth (PO), for the treatment period lasting 16 weeks. macitentan: 10mg macitentan tablets
Change in 6 Minute Walk Distance (6MWD)	-89 meters

SECONDARY outcome

Timeframe: Baseline, 16 weeks

The Borg Dyspnea Index (BDI) is a 0 to 10 rated self reported numerical score used to measure dyspnea during submaximal exercise and will be administered immediately following the 6MWT. The higher the score, the more dyspnea.

Outcome measures

Outcome measures
Measure	Macitentan n=1 Participants 10mg macitentan tablets, taken once daily (QD), by mouth (PO), for the treatment period lasting 16 weeks. macitentan: 10mg macitentan tablets
Assess Change of Borg Dyspnea Index	6 score on a scale

SECONDARY outcome

Timeframe: 16 weeks

The WHO functional classification will be assessed and documented with the WHO Class. Class I Patients with pulmonary hypertension (PH) but without resulting limitation of physical activity. Ordinary physical activity does not cause undue dyspnea or fatigue, chest pain or near syncope. Class II Patients with PH resulting in a slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity causes undue dyspnea or fatigue, chest pain or near syncope. Class III Patients with PH resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes undue dyspnea or fatigue, chest pain or near syncope. Class IV Patients with PH with inability to carry out any physical activity without symptoms. These patients manifest signs of right heart failure. Dyspnea and/or fatigue may even be present at rest. Discomfort is increased by any physical activity. The Class is inversely related to function.

Outcome measures

Outcome measures
Measure	Macitentan n=1 Participants 10mg macitentan tablets, taken once daily (QD), by mouth (PO), for the treatment period lasting 16 weeks. macitentan: 10mg macitentan tablets
World Health Organization (WHO) Functional Classification Class 1	0 participants
World Health Organization (WHO) Functional Classification Class 2	0 participants
World Health Organization (WHO) Functional Classification Class 3	1 participants
World Health Organization (WHO) Functional Classification Class 4	0 participants

SECONDARY outcome

Timeframe: Baseline, 16 weeks

The normal range for NT-pro-BNP is less than 300 picograms of BNP per milliliter (pg/ml) of blood; higher levels are less favorable.

Outcome measures

Outcome measures
Measure	Macitentan n=1 Participants 10mg macitentan tablets, taken once daily (QD), by mouth (PO), for the treatment period lasting 16 weeks. macitentan: 10mg macitentan tablets
Change in NT-proB-type Natriuretic Peptide (NT-pro-BNP)	10528 pg/mL

SECONDARY outcome

Timeframe: Baseline, Week 16

Cardiac output (CO) will be measured in L/min/m\^2. The normal range for CO is 4 to 8 L/min/m\^2.

Outcome measures

Outcome measures
Measure	Macitentan n=1 Participants 10mg macitentan tablets, taken once daily (QD), by mouth (PO), for the treatment period lasting 16 weeks. macitentan: 10mg macitentan tablets
Change in Cardiac Output (CO)	.29 L/min/m^2

Adverse Events

Macitentan

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Macitentan n=1 participants at risk 10mg macitentan tablets, taken once daily (QD), by mouth (PO), for the treatment period lasting 16 weeks. macitentan: 10mg macitentan tablets
Gastrointestinal disorders nausea and vomiting	100.0% 1/1 • Number of events 6 • 20 weeks

Additional Information

Elizabeth Klings, MD

Bosotn Medical Center

Phone: 617-638-7480

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place