ClinicalTrials.gov
ClinicalTrials.gov Menu

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 : Enrolling by invitation
First Posted : January 8, 2016
Last Update Posted : January 16, 2019
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 1

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
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
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 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. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: Baseline to Post-Treatment Follow-up Visit (Apx Wk 20) ]
    Assess the rate of adverse and serious adverse events in SCD patients taking macitentan


Secondary Outcome Measures :
  1. Assess change in Right atrial pressure (RAP), Right ventricular pressure (RVP), Systolic pulmonary artery pressure (SPAP), and Diastolic pulmonary artery pressure (PADP), measured in mmHg. [ Time Frame: Baseline to Week 16 ]

    Assess the change in the following hemodynamic parameters, by right heart catheterization, from baseline after 16 weeks of 10 mg daily of macitentan:

    Right atrial pressure (RAP) Right ventricular pressure (RVP) Systolic pulmonary artery pressure (SPAP) Diastolic pulmonary artery pressure (PADP)


  2. Assess change in Cardiac output (CO) measured in L/min [ Time Frame: Baseline to Week 16 ]

    Assess the change in the following hemodynamic parameters, by right heart catheterization, from baseline after 16 weeks of 10 mg daily of macitentan:

    Cardiac output (CO)


  3. Assess change in Cardiac index (CI) measured in L/min/m^2 [ Time Frame: Baseline to Week 16 ]

    Assess the change in the following hemodynamic parameters, by right heart catheterization, from baseline after 16 weeks of 10 mg daily of macitentan:

    Cardiac index (CI)


  4. Assess change in systemic vascular resistance measured by the following formula: Systemic Vascular Resistance (SVR) = 80x(Mean Arterial Pressure - Mean Venous Pressure or CVP) / Cardiac Output [ Time Frame: Baseline to Week 16 ]

    Assess the change in the following hemodynamic parameters, by right heart catheterization, from baseline after 16 weeks of 10 mg daily of macitentan:

    Systemic vascular resistance (SVR) Right ventricular function assessed by pressure-volume loop measurements


  5. Assess change in Right ventricular function assessed by pressure-volume loop measurements [ Time Frame: Baseline to Week 16 ]

    Assess the change in the following hemodynamic parameters, by right heart catheterization, from baseline after 16 weeks of 10 mg daily of macitentan:

    Right ventricular function assessed by pressure-volume loop measurements


  6. Assess change in 6 minute walk test [ Time Frame: Baseline to Week 16 ]
    Assess the change from baseline in 6MWT after 16 weeks of 10 mg daily macitentan

  7. Assess change of Borg Dyspnea Index [ Time Frame: Baseline to Week 16 ]
    Assess the change from baseline of Borg Dyspnea Index (BDI) after 16 weeks of 10 mg daily macitentan

  8. Assess change in NYHA/WHO functional classification [ Time Frame: Baseline to Week 16 ]
    Assess the change from baseline in NYHA/WHO functional classification after 16 weeks of 10 mg daily macitentan

  9. Assess change in cardiac biomarkers (BNP, NT-pro-BNP) [ Time Frame: Baseline to Week 16 ]
    Assess the change from baseline in cardiac biomarkers (e.g., BNP, NT-pro-BNP) after 16 weeks of 10 mg daily macitentan



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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 PAP ≥25 mmHg at rest). Left ventricular ejection fraction > 50%.
  4. Right heart catheterization which demonstrates the following:

    1. mPAP > 25 mmHg
    2. 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
United States, Massachusetts
Boston University School of Medicine
Boston, Massachusetts, United States, 02118
Sponsors and Collaborators
Boston University
Actelion
Investigators
Principal Investigator: Elizabeth Klings, MD Boston University

Publications:

Responsible Party: Boston University
ClinicalTrials.gov Identifier: NCT02651272     History of Changes
Other Study ID Numbers: H-33165
First Posted: January 8, 2016    Key Record Dates
Last Update Posted: January 16, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Currently there is no plan to share IPD.

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:
Hypertension
Hypertension, Pulmonary
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