Clinical trial NCT01036802 (phase 2, status: terminated)
Conditions: pulmonary hypertension
ICD codes: I27.0, I27.20, I27.21, I27.24, I27.29, P29.30, I27.22
Drugs: warfarin, placebo
SMILES: S1SSSSSSS1, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Reason stopped: 
    difficulty in accruing subjects
  
Eligibility criteria:

        Inclusion Criteria:

          -  At least 16 years of age

          -  Have a confirmed diagnosis of sickle cell anemia (HbSS) or sickle cell beta zero
             thalassemia

          -  Have evidence of persistent elevation of pulmonary artery systolic pressure on Doppler
             echocardiography (TR jet velocity of 2.5 to 2.9 m/s [or estimated pulmonary artery
             systolic pressure above the upper limit of reference adjusted ranges and up to 45 mm
             Hg]), but no evidence of moderate or severe diastolic dysfunction on tissue Doppler
             echocardiography. Mild PHT must be confirmed on repeat evaluation, at least 3 months
             later

          -  Have a serum creatinine =/< 1.5 mg/dl

          -  Have serum transaminase values (ALT) < 2 times upper limits of normal

          -  Have serum albumin =/> 3.2 g/dl

          -  Have a platelet count =/< 150,000 cu/mm

          -  Have normal baseline coagulation profile (PT/PTT)

          -  Patients on treatment with hydroxyurea should be on a stable dose for at least 6
             months. Doses of hydroxyurea may only be adjusted during the course of the study for
             safety reasons.

          -  Be able to understand the requirements of the study and be willing to give informed
             consent.

          -  Women of childbearing age must be practicing (and will continue to practice for the
             course of the study) an adequate method of contraception.

        Exclusion Criteria:

          -  Have a baseline hemoglobin < 6.0 gm/dl

          -  Have congenital heart disease, valvular heart disease, and other identified cause of
             pulmonary hypertension (including pulmonary fibrosis) unrelated to SCD

          -  Have an elevated pulmonary capillary wedge pressure, as evidenced by E/Em > 15 by
             pulsed wave and tissue Doppler imaging

          -  Have no measurable tricuspid regurgitant velocity on echocardiography

          -  Have a history of major gastrointestinal bleeding or a bleeding diathesis

          -  Have sickle cell complications such as recent vaso-occlusive crisis or acute chest
             syndrome, 4-weeks prior to commencing the study

          -  Have a history of clinically overt stroke(s) or seizures

          -  Have a brain magnetic resonance imaging/magnetic resonance angiography scan with
             evidence of Moya Moya within the preceding year

          -  Are pregnant or breastfeeding

          -  Are on chronic anticoagulant therapy

          -  Have a history of metastatic cancer

          -  Are chronically on therapy with aspirin or non-steroidal anti-inflammatory agents

          -  Are on a chronic transfusion program or have received a blood transfusion in the prior
             8 weeks

          -  Have a positive urine toxicology screen for cocaine and amphetamines

          -  Have a history of alcohol abuse

          -  Are currently receiving treatment with epoprostenol (or similar prostacyclin analog),
             sildenafil (or similar phosphodiesterase 5 inhibitor), bosentan or arginine

          -  Have ingested any investigational drugs within the past 4 weeks.