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Macitentan in Pulmonary Hypertension of Sickle Cell Disease (MENSCH)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02651272
Recruitment Status : Terminated (Unable to enroll IRB approved sample of participants.)
First Posted : January 8, 2016
Results First Posted : December 8, 2020
Last Update Posted : December 8, 2020
Sponsor:
Collaborator:
Actelion
Information provided by (Responsible Party):
Boston University

Brief Summary:
This is a pilot study to assess the safety and efficacy of macitentan in patients with pulmonary hypertension of sickle cell disease. This study will enroll approximately 10 subjects. Study participation for each subject will last approximately 24 weeks from screening to end of treatment follow-up.

Condition or disease Intervention/treatment Phase
Pulmonary Hypertension Sickle Cell Disease Drug: macitentan Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 4 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description: Study is Open Label
Primary Purpose: Other
Official Title: The Safety and Efficacy of Macitentan for Treatment of Pulmonary Hypertension in Sickle Cell Disease
Study Start Date : July 2015
Actual Primary Completion Date : December 18, 2019
Actual Study Completion Date : December 18, 2019


Arm Intervention/treatment
Experimental: macitentan
10mg macitentan tablets, taken once daily (QD), by mouth (PO), for the treatment period lasting 16 weeks.
Drug: macitentan
10mg macitentan tablets
Other Name: opsumit




Primary Outcome Measures :
  1. Number of Participants With Treatment-emergent Adverse Events [ Time Frame: 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.


Secondary Outcome Measures :
  1. Change in Right Arterial Pressure (RAP) [ Time Frame: Baseline, 16 weeks ]
    RAP will be assessed by right heart catheterization. Normal range is 2-6 mmHg.

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

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

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

  5. Change in Systemic Vascular Resistance Index (SVR) [ Time Frame: 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.

  6. Change in Cardiac Index (CI) [ Time Frame: 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.

  7. Change in 6 Minute Walk Distance (6MWD) [ Time Frame: 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.

  8. Assess Change of Borg Dyspnea Index [ Time Frame: 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.

  9. World Health Organization (WHO) Functional Classification [ Time Frame: 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.


  10. Change in NT-proB-type Natriuretic Peptide (NT-pro-BNP) [ Time Frame: 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.

  11. Change in Cardiac Output (CO) [ Time Frame: 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. A diagnosis of sickle cell disease (HbSS, HbSC, HbS- β+ or 0) confirmed by hemoglobin electrophoresis
  2. Provision of informed consent
  3. Suspicion of Pulmonary Hypertension by echocardiography within the last 6 months (RVSP > 40mmHg or a TRV > 3.0 m/sec) or diagnosis of Pulmonary Hypertension by cardiac catheterization within the last 12 months (mean Pulmonary Artery Pressure [PAP] ≥25 mmHg at rest). Left ventricular ejection fraction > 50%.
  4. Right heart catheterization which demonstrates the following:

    1. mean pulmonary arterial pressure [mPAP] > 25 mmHg
    2. pulmonary artery occluded pressure [PAOP] or LVEDP < 15 mmHg
    3. PVR > 160 dynes-sec/cm5 or 2 Wood Units
  5. Age > 18 years
  6. NYHA Class II or III by symptoms
  7. Six minute walk distance (6MWD) > 150 meters and < 450 meters
  8. A woman of child-bearing potential is eligible only if the following applies:

    1. Negative pre-treatment serum pregnancy test and agreement to monthly tests
    2. Use of two highly effective methods of contraception if not truly abstinent with a male partner OR permanent female sterilization has been performed.
  9. May be on background therapy or may be treatment naïve.

Exclusion Criteria:

  1. Current pregnancy or lactation
  2. Any one of the following medical conditions:

    1. Stroke within the last 6 weeks
    2. New diagnosis of pulmonary embolism within the last 3 months
    3. Clinically significant laboratory abnormalities, including, but not limited to: Positive Hepatitis B surface antigen or Hepatitis C antibody, Positive HIV test, Serum alanine aminotransferase (ALT) greater than or equal to 2.0 x ULN, Serum creatinine greater than or equal to 2.5mg/dL (or calculated creatinine clearance less than or equal to 30mL/min).
    4. Hospitalization within the prior 4 weeks for a vasoocclusive crisis or acute chest syndrome
    5. Any unstable (acute or chronic) condition that in the opinion of the investigator will prevent completion of the study
  3. Evidence of diastolic dysfunction of the left ventricle as defined by a mPAP > 25 mmHg and PCWP or LVEDP > 15 mmHg by right heart catheterization with a normal left ventricular ejection fraction by echocardiogram or MUGA.
  4. Left ventricular ejection fraction < 50% of significant ischemic, valvular or constrictive heart disease
  5. Acute or chronic impairment (other than dyspnea) limiting the ability to comply with study requirements (particularly the 6MWT) e.g. symptomatic hip osteonecrosis
  6. Active therapy with an IV prostacyclin
  7. Subjects who are taking other investigational medications at the time of the study
  8. Clinically significant psychiatric, addictive (defined by DSM-IV criteria), neurologic disease or condition that, in the opinion of the Investigator, would compromise his/her ability to give informed consent, participate fully in this study, or prevent adherence to the requirements of the study protocol.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02651272


Locations
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United States, Massachusetts
Boston University School of Medicine
Boston, Massachusetts, United States, 02118
Sponsors and Collaborators
Boston University
Actelion
Investigators
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Principal Investigator: Elizabeth Klings, MD Boston University
  Study Documents (Full-Text)

Documents provided by Boston University:
Publications:

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Responsible Party: Boston University
ClinicalTrials.gov Identifier: NCT02651272    
Other Study ID Numbers: H-33165
First Posted: January 8, 2016    Key Record Dates
Results First Posted: December 8, 2020
Last Update Posted: December 8, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Currently there is no plan to share IPD.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Boston University:
Pulmonary Hypertension
Sickle Cell Disease
Pulmonary Arterial Hypertension
Macitentan
Additional relevant MeSH terms:
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Hypertension, Pulmonary
Hypertension
Anemia, Sickle Cell
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Macitentan
Endothelin A Receptor Antagonists
Endothelin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Endothelin B Receptor Antagonists