Macitentan in Pulmonary Hypertension of Sickle Cell Disease
Condition: Pulmonary Hypertension; Sickle Cell Disease
MeSH terms: Hypertension, Pulmonary; Hypertension; Anemia, Sickle Cell
Intervention: macitentan
Intervention description: 10mg macitentan tablets
Intervention MeSH terms: Macitentan
Phase: Phase 2
Study type: Interventional
Primary purpose: Other
Intervention model: Single Group Assignment
Masking: None (Open Label)
Masking description: Study is Open Label
Enrollment: 4.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Pulmonary Hypertension; Sickle Cell Disease; Pulmonary Arterial Hypertension; Macitentan

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.
    

Eligibility 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.