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

Sponsored by:	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

Genetics Home Reference related topics: pulmonary arterial hypertension

MedlinePlus related topics: High Blood Pressure Pulmonary Hypertension

Drug Information available for: Simvastatin Acetylsalicylic acid

U.S. FDA Resources

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

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:	128
Study Start Date:	September 2006
Estimated Study Completion Date:	March 2010
Estimated Primary Completion Date:	March 2010 (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	Recruiting
Baltimore, Maryland, United States, 21205
Contact: Jude Aidam 410-614-1316 jaidam1@jhu.edu
Principal Investigator: Reda E. Girgis, MB, BCh
Sub-Investigator: Paul Hassoun, MD
Sub-Investigator: Wendy Post, MD, MS
Sub-Investigator: Ari Zaiman, MD, PhD
United States, Massachusetts
Tufts University School of Medicine	Recruiting
Boston, Massachusetts, United States, 02110
Contact: Karen Visnaw, RN 617-636-1334 KVisnaw@tufts-nemc.org
Principal Investigator: Kari Roberts, MD
Sub-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
United States, New York
Columbia University	Recruiting
New York, New York, United States, 10032
Contact: Debbie Rybak 212-305-5836 dr2359@columbia.edu
Contact: Nisha Philip, MD 212-305-7720 np2173@columbia.edu
Principal Investigator: David J. Lederer, MD, MS
Sub-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
United States, Pennsylvania
University of Pennsylvania	Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Michael Harhay 215-662-9720 Michael.Harhay@uphs.upenn.edu
Contact: Darren Taichman, MD darren.taichman@uphs.upenn.edu
Principal Investigator: Steven M Kawut, MD, MS
Sub-Investigator: Darren Taichman, MD

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

Responsible Party:	Columbia University College of P & S ( Steven Kawut, MD, MS )
Study ID Numbers:	458, R01 HL082895-01
Study First Received:	September 30, 2006
Last Updated:	December 5, 2008
ClinicalTrials.gov Identifier:	NCT00384865
Health Authority:	United States: Federal Government

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

Pulmonary Arterial Hypertension

Study placed in the following topic categories:

Idiopathic pulmonary hypertension
Aspirin
Respiratory Tract Diseases
Simvastatin

Hypertension, Pulmonary
Lung Diseases
Vascular Diseases
Hypertension

Additional relevant MeSH terms:

Antimetabolites
Anti-Inflammatory Agents
Molecular Mechanisms of Pharmacological Action
Antilipemic Agents
Cyclooxygenase Inhibitors
Hematologic Agents
Physiological Effects of Drugs
Enzyme Inhibitors
Fibrinolytic Agents
Anticholesteremic Agents
Cardiovascular Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors

Pharmacologic Actions
Fibrin Modulating Agents
Analgesics, Non-Narcotic
Sensory System Agents
Therapeutic Uses
Platelet Aggregation Inhibitors
Cardiovascular Diseases
Anti-Inflammatory Agents, Non-Steroidal
Analgesics
Peripheral Nervous System Agents
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 16, 2009