A Study of Aspirin and Simvastatin in Pulmonary Arterial Hypertension - Full Text View

Sponsor:	National Heart, Lung, and Blood Institute (NHLBI)
Information provided by:	National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:	NCT00384865

Purpose

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

Condition	Intervention	Phase
Hypertension, Pulmonary	Drug: Simvastatin Drug: Aspirin Drug: Placebo	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Factorial Assignment, Safety/Efficacy Study
Official Title:	A Clinical Trial of Aspirin and Simvastatin in Pulmonary Arterial Hypertension

Resource links provided by NLM:

Genetics Home Reference related topics: pulmonary arterial hypertension

MedlinePlus related topics: High Blood Pressure Pulmonary Hypertension

Drug Information available for: Acetylsalicylic acid Simvastatin

U.S. FDA Resources

Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Primary Outcome Measures:

Distance walked in six minutes [ Time Frame: Measured at 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Platelet markers [ Time Frame: Measured at 6 months ] [ Designated as safety issue: No ]
Endothelial function [ Time Frame: Measured at 6 months ] [ Designated as safety issue: No ]
World Health Organization (WHO) functional class [ Time Frame: Measured at 6 months ] [ Designated as safety issue: No ]
Addition of PAH medication [ Time Frame: Measured at 6 months ] [ Designated as safety issue: No ]
Time to clinical events [ Time Frame: Measured at 6 months ] [ Designated as safety issue: Yes ]
Adverse events [ Time Frame: Measured at 6 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	92
Study Start Date:	September 2006
Estimated Study Completion Date:	March 2011
Estimated Primary Completion Date:	March 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator Aspirin 81 mg + Simvastatin 40 mg	Drug: Simvastatin Simvastatin 40 mg, taken orally, once a day for 6 months Drug: Aspirin Aspirin 81 mg, taken orally, once a day for 6 months
2: Active Comparator Aspirin 81 mg + Placebo	Drug: Aspirin Aspirin 81 mg, taken orally, once a day for 6 months Drug: Placebo Placebo, taken orally, once a day for 6 months
3: Active Comparator Placebo + Simvastatin 40 mg	Drug: Simvastatin Simvastatin 40 mg, taken orally, once a day for 6 months Drug: Placebo Placebo, taken orally, once a day for 6 months
4: Placebo Comparator Placebo + Placebo	Drug: Placebo Placebo, taken orally, once a day for 6 months

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00384865

Locations

United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21205
United States, Massachusetts
Tufts University School of Medicine
Boston, Massachusetts, United States, 02110
United States, New York
Columbia University
New York, New York, United States, 10032
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104

Sponsors and Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Principal Investigator:	Steven M Kawut, MD, MS	University of Pennsylvania
Principal Investigator:	David J Lederer, MD, MS	Columbia University
Principal Investigator:	Reda E Girgis, MB, BCh	Johns Hopkins University
Principal Investigator:	Kari E Roberts, MD	Tufts University

More Information

No publications provided

Responsible Party:	University of Pennsylvania ( Steven Kawut, MD, MS )
Study ID Numbers:	458, R01 HL082895-01
Study First Received:	September 30, 2006
Last Updated:	October 8, 2009
ClinicalTrials.gov Identifier:	NCT00384865 History of Changes
Health Authority:	United States: Federal Government

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

Pulmonary Arterial Hypertension

Additional relevant MeSH terms:

Antimetabolites
Anti-Inflammatory Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Hematologic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Aspirin
Respiratory Tract Diseases
Sensory System Agents
Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal
Cardiovascular Diseases
Analgesics
Simvastatin

Antilipemic Agents
Cyclooxygenase Inhibitors
Vascular Diseases
Enzyme Inhibitors
Anticholesteremic Agents
Cardiovascular Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Pharmacologic Actions
Analgesics, Non-Narcotic
Hypertension, Pulmonary
Lung Diseases
Platelet Aggregation Inhibitors
Peripheral Nervous System Agents
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on February 08, 2010