A Study of Aspirin and Simvastatin in Pulmonary Arterial Hypertension

Hypertension, Pulmonary Clinical Trial

Official title:

A Clinical Trial of Aspirin and Simvastatin in Pulmonary Arterial Hypertension

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00384865
• Other study ID #: 458
• Secondary ID: R01HL082895-01
• Status: Terminated
• Phase: Phase 2
• First received: September 30, 2006
• Last updated: July 18, 2017
• Start date: September 2006
• Est. completion date: October 2009

Study information

• Verified date: July 2017
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Description:

PAH is characterized by dyspnea, fatigue, and lower extremity edema as a result of heart failure. In PAH, in situ thrombosis may occur in the lungs, and pulmonary endothelial dysfunction is well-recognized. As aspirin inhibits platelet aggregation, there may be value in using aspirin to treat PAH. Simvastatin has beneficial effects on blood vessels in other types of cardiovascular disease. Therefore, simvastatin may similarly benefit patients with PAH.

Participants in this study will be randomly assigned to receive 6 months of daily placebo tablets, daily aspirin and daily placebo, daily simvastatin and daily placebo, or daily aspirin and daily simvastatin in a double-blind fashion. The study will compare the safety and efficacy of aspirin to placebo and simvastatin to placebo.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 64
• Est. completion date: October 2009
• Est. primary completion date: October 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Familial Primary Pulmonary Hypertension
• Hypertension
• Hypertension, Pulmonary

Intervention

Drug:
• Simvastatin
Simvastatin 40 mg, taken orally, once a day for 6 months
• Aspirin
Aspirin 81 mg, taken orally, once a day for 6 months
• Placebo
Placebo, taken orally, once a day for 6 months

Locations

Country	Name	City	State
United States	Johns Hopkins University	Baltimore	Maryland
United States	Tufts University School of Medicine	Boston	Massachusetts
United States	Columbia University	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
University of Pennsylvania	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Kawut SM, Bagiella E, Lederer DJ, Shimbo D, Horn EM, Roberts KE, Hill NS, Barr RG, Rosenzweig EB, Post W, Tracy RP, Palevsky HI, Hassoun PM, Girgis RE; ASA-STAT Study Group. Randomized clinical trial of aspirin and simvastatin for pulmonary arterial hyper — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Distance Walked in Six Minutes		Measured at 6 months
Secondary	Time to Clinical Worsening Events (Number of Events)	Defined by the addition of new PAH therapies or dose increases in previously stable PAH therapy, hospitalization for right-sided heart failure, lung transplantation, atrial septostomy, and cardiovascular and all-cause death.	Measured at 6 months
Secondary	Adverse Events	Please refer to the Adverse Event Tables for specific information	Measured at 6 months