Clinical trial NCT00492531 (phase 2, status: terminated)
Conditions: sickle cell disease, pulmonary hypertension
ICD codes: D57.1, D57.20, D57.212, D57.219, D57.211, D57.213, D57.218, I27.0, I27.20, I27.21, I27.24, I27.29, P29.30, I27.22
Drugs: sildenafil, placebo
SMILES: CCCC1=NN(C)C2=C1NC(=NC2=O)C1=C(OCC)C=CC(=C1)S(=O)(=O)N1CCN(C)CC1, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Reason stopped: 
    subjects on drug were more likely to have severe pain crises requiring hospitalization.
  
Eligibility criteria:

        • Eligibility based on the following inclusion and exclusion criteria.

        INCLUSION CRITERIA:

        Screening Phase:

          -  Males or females, greater than or equal to 12 years of age and less than or equal to
             70 years of age.

          -  Diagnosis of sickle cell disease (including, but not limited to SS, SC, SD, or S-beta
             zero thalassemia).

          -  Provision of informed consent and, where applicable, assent.

        Observational Follow-up Study:

          -  Satisfaction of screening criteria.

          -  In the opinion of the investigator, ability to maintain follow-up contact.

          -  Failure to satisfy the eligibility requirements of the Main Interventional Trial (MIT)
             OR discontinuation/completion of the MIT/Open-label Follow-up Phase.

          -  Provision of informed consent and, where applicable, assent.

        Main Interventional Trial:

          -  Males or females, 12 years of age or older and less than or equal to 70 years of age.

          -  Female subjects, on a reliable method of birth control or not physically able to bear
             children.

          -  Electrophoretic documentation of sickle cell disease (including, but not limited to
             SS, SC, SD, or S-beta zero thalassemia).

          -  At least mild pulmonary hypertension with TRV greater than or equal to 2.7 m/sec by
             echocardiogram.

          -  Six-minute walk distance of 150-500 m.

          -  In the opinion of the investigator, able to complete the protocol scheduled
             assessments during the 16-week, double-blind phase.

          -  Provision of informed consent and, where applicable, assent.

          -  Subjects with systemic hypertension must be on a stable antihypertensive regimen for
             greater than or equal to 90 days and a stable dose for greater than or equal to 30
             days.

        EXCLUSION CRITERIA:

        Current pregnancy or lactation.

        Any one of the following medical conditions:

          -  Stroke within the last six weeks.

          -  Diagnosis of pulmonary embolism within the last three months.

          -  History of retinal detachment or retinal hemorrhage in the last 6 months.

          -  Non-arteritic anterior ischemic optic neuropathy (NAION) in one or both eyes.

          -  History of sustained priapism requiring medical or surgical treatment, unless
             currently impotent or on transfusion program within the last two years.

          -  Any unstable (chronic or acute) condition that in the opinion of the investigator will
             prevent completion of the study.

        Subjects taking nitrate-based vasodilators (including, but not limited to nicorandil
        [available in the UK only]), prostacyclin (inhaled, subcutaneous or intravenous) or
        endothelin antagonists. Subjects taking calcium channel blockers will be allowed to
        participate if they are on a stable dose for greater than or equal to 3 months.

        Left ventricular ejection fraction (LVEF) less than 40 percent or clinically significant
        ischemic, valvular or constrictive heart disease: LVEF less than 40 percent or SF less than
        22 percent.

        Subjects in other research studies with investigational drugs (with the exception of
        hydroxyurea) unless the other trial has been approved by the walk-PHaSST Executive
        Committee for co-participation.

        Acute or chronic impairment (other than dyspnea), limiting the ability to comply with study
        requirements (in particular with 6MWT), e.g., angina pectoris, intermittent claudication,
        symptomatic hip osteonecrosis.

        Tonsillectomies for sleep apnea within 3 months prior to randomization. Active therapy for
        pulmonary hypertension, including prostacyclin analog, endothelin-1 antagonist, or PDE-5
        inhibitor.

        Protease inhibitor therapy for HIV treatment Subjects taking potent CYP3A4 inhibitor
        therapy (e.g., itraconazole, ritonavir, ketoconazole) Subjects who are anticoagulated and
        have proliferative retinopathy (unless they have had ophthalmologist recommended
        intervention (e.g., phototherapy) or have been cleared by the ophthalmologist to
        participate in the study.

        Subjects with systolic blood pressure greater than or equal to 140 mmHg OR diastolic blood
        pressure greater than or equal to 90 mmHg.