A Study of Aspirin and Simvastatin in Pulmonary Arterial Hypertension
Condition: Hypertension, Pulmonary
MeSH terms: Pulmonary Arterial Hypertension; Hypertension, Pulmonary; Hypertension
Intervention: Simvastatin; Aspirin; Placebo
Intervention description: Simvastatin 40 mg, taken orally, once a day for 6 months; Aspirin 81 mg, taken orally, once a day for 6 months; Placebo, taken orally, once a day for 6 months
Intervention MeSH terms: Aspirin; Simvastatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 64.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Pulmonary Arterial Hypertension

Summary:

      The purpose of this study is to determine whether aspirin and simvastatin are safe and
      effective for the treatment of pulmonary arterial hypertension (PAH).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Mean pulmonary artery pressure greater than 25 mm Hg at rest with a pulmonary
             capillary wedge pressure less than 16 mm Hg

          -  Diagnosis of PAH that is a) idiopathic, b) familial, or c) associated with collagen
             vascular disease, HIV infection, congenital systemic-to-pulmonary shunt, or former
             anorexigen use

          -  Most recent pulmonary function tests showing FEV1/FVC ratio greater than 50% AND one
             of the following conditions: a) total lung capacity greater than 70% predicted, or b)
             total lung capacity between 60% and 70% of predicted value with no more than mild
             patchy interstitial lung disease on high resolution computerized tomography of the
             chest

          -  Ability to perform six-minute walk testing without limitations in musculoskeletal
             function or coordination

          -  Negative pregnancy test at screening visit for women of childbearing potential

          -  If female, willing to use adequate form of birth control

        Exclusion Criteria:

          -  PAH related to other etiologies

          -  Diagnosis of sickle cell disease

          -  Clinically significant untreated sleep apnea, as diagnosed by polysomnography

          -  Left-sided valvular disease (more than moderate mitral valve stenosis or insufficiency
             or aortic stenosis or insufficiency), pulmonary artery or valve stenosis, or ejection
             fraction less than 45% on echocardiography

          -  Hospitalized or acutely ill

          -  Kidney failure

          -  Initiation of PAH therapy (prostacyclin analogues, endothelin [ET]-1 receptor
             antagonists, phosphodiesterase [PDE]-5 inhibitors) within 3 months of study entry

          -  Allergy or hypersensitivity to aspirin or simvastatin

          -  Absolute indication for aspirin or other anti-platelet therapy

          -  Current treatment with statin therapy

          -  Inability or unwillingness to avoid non-steroidal, anti-inflammatory medications for 6
             months following study entry

          -  Current or recent use or planned treatment with one of the following: amiodarone,
             cyclosporine, itraconazole, ketoconazole, erythromycin, clarithromycin, HIV protease
             inhibitors, nefazodone, cimetidine, danazol, large quantities of grapefruit juice
             (more than 1 quart daily), verapamil, fibrates, or niacin

          -  Peptic or duodenal ulcer diagnosed within 1 year of study entry

          -  Gastrointestinal bleeding within 6 months prior of study entry

          -  Bleeding diathesis

          -  History of intracranial bleeding

          -  Anemia (hematocrit less than 30%) at screening

          -  International normalized ratio (INR) greater than 3.0 at screening

          -  Severe thrombocytopenia (less than 75,000/L) at screening

          -  Hepatic transaminases greater than twice the upper limit of normal at screening

          -  Chronic liver disease (e.g., cirrhosis, chronic hepatitis) with portal hypertension

          -  Current or recent (within 6 months of study entry) chronic heavy alcohol consumption

          -  History of myositis

          -  Creatine phosphokinase (CPK) greater than 1.5 times the upper limit of normal at
             screening

          -  Abnormalities of the arm or hand or past radical mastectomy that might prevent
             brachial artery ultrasound

          -  Pregnant or breastfeeding

          -  Current use of another investigational drug for PAH

          -  Received a lung transplant