A Study of Aspirin and Simvastatin in Pulmonary Arterial Hypertension

• Status: Terminated
• Trial end date: 2009-10-01
• Target enrollment: 0
• Participant gender: All

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).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Pennsylvania
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Treatments: Aspirin; Simvastatin

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