A Study of Aspirin and Simvastatin in Pulmonary Arterial Hypertension

Condition(s) targeted: Hypertension, Pulmonary

Intervention: Simvastatin (Drug); Aspirin (Drug); Placebo (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: National Heart, Lung, and Blood Institute (NHLBI)

Official(s) and/or principal investigator(s):
Steven M Kawut, MD, MS, Principal Investigator, Affiliation: University of Pennsylvania
David J Lederer, MD, MS, Principal Investigator, Affiliation: Columbia University
Reda E Girgis, MB, BCh, Principal Investigator, Affiliation: Johns Hopkins University
Kari E Roberts, MD, Principal Investigator, Affiliation: Tufts University

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

Official title: A Clinical Trial of Aspirin and Simvastatin in Pulmonary Arterial Hypertension

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Factorial Assignment, Safety/Efficacy Study

Primary outcome: Distance walked in six minutes

Secondary outcome:

Platelet markers

Endothelial function

World Health Organization (WHO) functional class

Addition of PAH medication

Time to clinical events

Adverse events

Detailed 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

Johns Hopkins University, Baltimore, Maryland 21205, United States; Recruiting
Jude Aidam, Phone: 410-614-1316, Email: jaidam1@jhu.edu
Reda E. Girgis, MB, BCh, Principal Investigator
Paul Hassoun, MD, Sub-Investigator
Wendy Post, MD, MS, Sub-Investigator
Ari Zaiman, MD, PhD, Sub-Investigator

Tufts University School of Medicine, Boston, Massachusetts 02110, United States; Recruiting
Karen Visnaw, RN, Phone: 617-636-1334, Email: KVisnaw@tufts-nemc.org
Tahiyyah Tai Muhammad, Phone: 617-636-3269, Email: tmuhammad@tuftsmedicalcenter.org
Kari Roberts, MD, Principal Investigator
Nicholas Hill, MD, Sub-Investigator
Ioana Preston, MD, Sub-Investigator
Karen Visnaw, RN, Sub-Investigator
Elaine Purcell, MD, Sub-Investigator
Samaan Rafeq, MD, Sub-Investigator
Archan Shah, MD, Sub-Investigator
Farhan Siddiqui, MD, Sub-Investigator

Columbia University, New York, New York 10032, United States; Recruiting
Debbie Rybak, Phone: 212-305-5836, Email: dr2359@columbia.edu
Nisha Philip, MBBS, Phone: 212-305-7720, Email: np2173@columbia.edu
David J. Lederer, MD, MS, Principal Investigator
Emilia Bagiella, PhD, Sub-Investigator
R. Graham Barr, MD, Sub-Investigator
Shunichi Homma, MD, Sub-Investigator
Evelyn Horn, MD, Sub-Investigator
Sudhir Marathe, PhD, Sub-Investigator
Daichi Shimbo, MD, Sub-Investigator

University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States; Recruiting
Diane Pinder, Phone: 215-662-9716, Email: pinder@mail.med.upenn.edu
Darren Taichman, MD, Email: darren.taichman@uphs.upenn.edu
Steven M Kawut, MD, MS, Principal Investigator
Darren Taichman, MD, Sub-Investigator

Starting date: September 2006
Ending date: March 2010
Last updated: February 11, 2009