Intervention: Macitentan
Trial phase: Phase 2
ATC code: C02KX04 | C02KX54
SMILES: CCCNS(=O)(=O)Nc1ncnc(OCCOc2ncc(Br)cn2)c1-c1ccc(Br)cc1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 1
Group description: 10mg macitentan tablets, taken once daily (QD), by mouth (PO), for the treatment period lasting 16 weeks.

macitentan: 10mg macitentan tablets
Eligibility criteria:
Inclusion Criteria:

A diagnosis of sickle cell disease (HbSS, HbSC, HbS- β+ or 0) confirmed by hemoglobin electrophoresis
Provision of informed consent
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%.

Right heart catheterization which demonstrates the following:

mean pulmonary arterial pressure [mPAP] > 25 mmHg
pulmonary artery occluded pressure [PAOP] or LVEDP < 15 mmHg
PVR > 160 dynes-sec/cm5 or 2 Wood Units
Age > 18 years
NYHA Class II or III by symptoms
Six minute walk distance (6MWD) > 150 meters and < 450 meters

A woman of child-bearing potential is eligible only if the following applies:

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

Exclusion Criteria:

Current pregnancy or lactation

Any one of the following medical conditions:

Stroke within the last 6 weeks
New diagnosis of pulmonary embolism within the last 3 months
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).
Hospitalization within the prior 4 weeks for a vasoocclusive crisis or acute chest syndrome
Any unstable (acute or chronic) condition that in the opinion of the investigator will prevent completion of the study
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.
Left ventricular ejection fraction < 50% of significant ischemic, valvular or constrictive heart disease
Acute or chronic impairment (other than dyspnea) limiting the ability to comply with study requirements (particularly the 6MWT) e.g. symptomatic hip osteonecrosis
Active therapy with an IV prostacyclin
Subjects who are taking other investigational medications at the time of the study
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.