Macitentan in Pulmonary Hypertension of Sickle Cell Disease (MENSCH)

• ClinicalTrials.gov Identifier: NCT02651272
• Recruitment Status: Terminated
• First Posted: January 8, 2016
• Results First Posted: December 8, 2020
• Last Update Posted: December 8, 2020
• Sponsor: Boston University
• Collaborator: Actelion
• Information provided by (Responsible Party): Boston University

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Other
• Conditions: Pulmonary Hypertension; Sickle Cell Disease
• Intervention: Drug: macitentan
• Enrollment: 4

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Macitentan
Arm/Group Description	10mg macitentan tablets, taken once daily (QD), by mouth (PO), for the treatment period lasting 16 weeks. macitentan: 10mg macitentan tablets
Period Title: Overall Study
Started	4
Completed	1
Not Completed	3

Baseline Characteristics

Arm/Group Title		Macitentan
Arm/Group Description		10mg macitentan tablets, taken once daily (QD), by mouth (PO), for the treatment period lasting 16 weeks. macitentan: 10mg macitentan tablets
Overall Number of Baseline Participants		4
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	4 participants
	<=18 years	0 0.0%
	Between 18 and 65 years	4 100.0%
	>=65 years	0 0.0%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	4 participants
	Female	2 50.0%
	Male	2 50.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	4 participants
	American Indian or Alaska Native	0 0.0%
	Asian	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	4 100.0%
	White	0 0.0%
	More than one race	0 0.0%
	Unknown or Not Reported	0 0.0%
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants
United States	Number Analyzed	4 participants
		4 100.0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events
Description	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.
Time Frame	20 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Macitentan
Arm/Group Description:	10mg macitentan tablets, taken once daily (QD), by mouth (PO), for the treatment period lasting 16 weeks. macitentan: 10mg macitentan tablets
Overall Number of Participants Analyzed	1
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%

2. Secondary Outcome

Title	Change in Right Arterial Pressure (RAP)
Description	RAP will be assessed by right heart catheterization. Normal range is 2-6 mmHg.
Time Frame	Baseline, 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Macitentan
Arm/Group Description:	10mg macitentan tablets, taken once daily (QD), by mouth (PO), for the treatment period lasting 16 weeks. macitentan: 10mg macitentan tablets
Overall Number of Participants Analyzed	1
Measure Type: Number; Unit of Measure: mmHg
	-5

3. Secondary Outcome

Title	Change in Systolic Right Ventricular Pressure (RVSP)
Description	RVSP will be assessed by right heart catheterization. Normal range is 15-25 mmHg.
Time Frame	Baseline, 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Macitentan
Arm/Group Description:	10mg macitentan tablets, taken once daily (QD), by mouth (PO), for the treatment period lasting 16 weeks. macitentan: 10mg macitentan tablets
Overall Number of Participants Analyzed	1
Measure Type: Number; Unit of Measure: mmHg
	3

4. Secondary Outcome

Title	Change in Diastolic Pulmonary Artery Pressure (PADP)
Description	PADP will be assessed by right heart catheterization. Normal range is 8-15 mmHg.
Time Frame	Baseline, 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Macitentan
Arm/Group Description:	10mg macitentan tablets, taken once daily (QD), by mouth (PO), for the treatment period lasting 16 weeks. macitentan: 10mg macitentan tablets
Overall Number of Participants Analyzed	1
Measure Type: Number; Unit of Measure: mmHg
	-5

5. Secondary Outcome

Title	Change in Systolic Pulmonary Artery Pressure (SPAP)
Description	SPAP will be assessed by right heart catheterization. Normal range is 15-25 mm Hg.
Time Frame	Baseline, 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Macitentan
Arm/Group Description:	10mg macitentan tablets, taken once daily (QD), by mouth (PO), for the treatment period lasting 16 weeks. macitentan: 10mg macitentan tablets
Overall Number of Participants Analyzed	1
Measure Type: Number; Unit of Measure: mmHg
	7

6. Secondary Outcome

Title	Change in Systemic Vascular Resistance Index (SVR)
Description	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.
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Macitentan
Arm/Group Description:	10mg macitentan tablets, taken once daily (QD), by mouth (PO), for the treatment period lasting 16 weeks. macitentan: 10mg macitentan tablets
Overall Number of Participants Analyzed	1
Measure Type: Number; Unit of Measure: dynes-sec/cm-5.
	-528

7. Secondary Outcome

Title	Change in Cardiac Index (CI)
Description	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.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Macitentan
Arm/Group Description:	10mg macitentan tablets, taken once daily (QD), by mouth (PO), for the treatment period lasting 16 weeks. macitentan: 10mg macitentan tablets
Overall Number of Participants Analyzed	1
Measure Type: Number; Unit of Measure: L/min/m^2
	.23

8. Secondary Outcome

Title	Change in 6 Minute Walk Distance (6MWD)
Description	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.
Time Frame	Baseline, 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Macitentan
Arm/Group Description:	10mg macitentan tablets, taken once daily (QD), by mouth (PO), for the treatment period lasting 16 weeks. macitentan: 10mg macitentan tablets
Overall Number of Participants Analyzed	1
Measure Type: Number; Unit of Measure: meters
	-89

9. Secondary Outcome

Title	Assess Change of Borg Dyspnea Index
Description	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.
Time Frame	Baseline, 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Macitentan
Arm/Group Description:	10mg macitentan tablets, taken once daily (QD), by mouth (PO), for the treatment period lasting 16 weeks. macitentan: 10mg macitentan tablets
Overall Number of Participants Analyzed	1
Measure Type: Number; Unit of Measure: score on a scale
	6

10. Secondary Outcome

Title	World Health Organization (WHO) Functional Classification
Description	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.
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Macitentan
Arm/Group Description:	10mg macitentan tablets, taken once daily (QD), by mouth (PO), for the treatment period lasting 16 weeks. macitentan: 10mg macitentan tablets
Overall Number of Participants Analyzed	1
Measure Type: Number; Unit of Measure: participants
Class 1	0
Class 2	0
Class 3	1
Class 4	0

11. Secondary Outcome

Title	Change in NT-proB-type Natriuretic Peptide (NT-pro-BNP)
Description	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.
Time Frame	Baseline, 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Macitentan
Arm/Group Description:	10mg macitentan tablets, taken once daily (QD), by mouth (PO), for the treatment period lasting 16 weeks. macitentan: 10mg macitentan tablets
Overall Number of Participants Analyzed	1
Measure Type: Number; Unit of Measure: pg/mL
	10528

12. Secondary Outcome

Title	Change in Cardiac Output (CO)
Description	Cardiac output (CO) will be measured in L/min/m^2. The normal range for CO is 4 to 8 L/min/m^2.
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Macitentan
Arm/Group Description:	10mg macitentan tablets, taken once daily (QD), by mouth (PO), for the treatment period lasting 16 weeks. macitentan: 10mg macitentan tablets
Overall Number of Participants Analyzed	1
Measure Type: Number; Unit of Measure: L/min/m^2
	.29

Adverse Events

Time Frame	20 weeks
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Macitentan
Arm/Group Description	10mg macitentan tablets, taken once daily (QD), by mouth (PO), for the treatment period lasting 16 weeks. macitentan: 10mg macitentan tablets
All-Cause Mortality
	Macitentan
	Affected / at Risk (%)
Total	0/1 (0.00%)
Serious Adverse Events
	Macitentan
	Affected / at Risk (%)	# Events
Total	0/1 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Macitentan
	Affected / at Risk (%)	# Events
Total	1/1 (100.00%)
Gastrointestinal disorders
nausea and vomiting †	1/1 (100.00%)	6
† Indicates events were collected by systematic assessment

Limitations and Caveats

Early termination as unable to enroll participants.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Elizabeth Klings, MD
• Organization: Bosotn Medical Center
• Phone: 617-638-7480
• EMail: elizabeth.klings@bmc.org

Publications:

Mehari A, Gladwin MT, Tian X, Machado RF, Kato GJ. Mortality in adults with sickle cell disease and pulmonary hypertension. JAMA. 2012 Mar 28;307(12):1254-6. doi: 10.1001/jama.2012.358. No abstract available.

Parent F, Bachir D, Inamo J, Lionnet F, Driss F, Loko G, Habibi A, Bennani S, Savale L, Adnot S, Maitre B, Yaici A, Hajji L, O'Callaghan DS, Clerson P, Girot R, Galacteros F, Simonneau G. A hemodynamic study of pulmonary hypertension in sickle cell disease. N Engl J Med. 2011 Jul 7;365(1):44-53. doi: 10.1056/NEJMoa1005565.

Fonseca GH, Souza R, Salemi VM, Jardim CV, Gualandro SF. Pulmonary hypertension diagnosed by right heart catheterisation in sickle cell disease. Eur Respir J. 2012 Jan;39(1):112-8. doi: 10.1183/09031936.00134410. Epub 2011 Jul 20.

Klings ES, Machado RF, Barst RJ, Morris CR, Mubarak KK, Gordeuk VR, Kato GJ, Ataga KI, Gibbs JS, Castro O, Rosenzweig EB, Sood N, Hsu L, Wilson KC, Telen MJ, Decastro LM, Krishnamurti L, Steinberg MH, Badesch DB, Gladwin MT; American Thoracic Society Ad Hoc Committee on Pulmonary Hypertension of Sickle Cell Disease. An official American Thoracic Society clinical practice guideline: diagnosis, risk stratification, and management of pulmonary hypertension of sickle cell disease. Am J Respir Crit Care Med. 2014 Mar 15;189(6):727-40. doi: 10.1164/rccm.201401-0065ST.

Barst RJ, Mubarak KK, Machado RF, Ataga KI, Benza RL, Castro O, Naeije R, Sood N, Swerdlow PS, Hildesheim M, Gladwin MT; ASSET study group*. Exercise capacity and haemodynamics in patients with sickle cell disease with pulmonary hypertension treated with bosentan: results of the ASSET studies. Br J Haematol. 2010 May;149(3):426-35. doi: 10.1111/j.1365-2141.2010.08097.x. Epub 2010 Feb 17.

Machado RF, Barst RJ, Yovetich NA, Hassell KL, Kato GJ, Gordeuk VR, Gibbs JS, Little JA, Schraufnagel DE, Krishnamurti L, Girgis RE, Morris CR, Rosenzweig EB, Badesch DB, Lanzkron S, Onyekwere O, Castro OL, Sachdev V, Waclawiw MA, Woolson R, Goldsmith JC, Gladwin MT; walk-PHaSST Investigators and Patients. Hospitalization for pain in patients with sickle cell disease treated with sildenafil for elevated TRV and low exercise capacity. Blood. 2011 Jul 28;118(4):855-64. doi: 10.1182/blood-2010-09-306167. Epub 2011 Apr 28.

• Responsible Party: Boston University
• ClinicalTrials.gov Identifier: NCT02651272
• Other Study ID Numbers: H-33165
• First Submitted: January 6, 2016
• First Posted: January 8, 2016
• Results First Submitted: October 22, 2020
• Results First Posted: December 8, 2020
• Last Update Posted: December 8, 2020