A Study of Aspirin and Simvastatin in Pulmonary Arterial Hypertension

This study has been terminated.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT00384865
First received: September 30, 2006
Last updated: January 31, 2013
Last verified: July 2009
  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 2

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

Resource links provided by NLM:


Further study details as provided by University of Pennsylvania:

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 ]

Enrollment: 64
Study Start Date: September 2006
Study Completion Date: October 2009
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Aspirin 81 mg + Simvastatin 40 mg
Drug: Simvastatin
Simvastatin 40 mg, taken orally, once a day for 6 months
Other Name: Zocor
Drug: Aspirin
Aspirin 81 mg, taken orally, once a day for 6 months
Active Comparator: 2
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
Active Comparator: 3
Placebo + Simvastatin 40 mg
Drug: Simvastatin
Simvastatin 40 mg, taken orally, once a day for 6 months
Other Name: Zocor
Drug: Placebo
Placebo, taken orally, once a day for 6 months
Placebo Comparator: 4
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
University of Pennsylvania
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 by University of Pennsylvania

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT00384865     History of Changes
Other Study ID Numbers: 458, R01HL082895-01
Study First Received: September 30, 2006
Last Updated: January 31, 2013
Health Authority: United States: Federal Government

Keywords provided by University of Pennsylvania:
Pulmonary Arterial Hypertension

Additional relevant MeSH terms:
Hypertension, Pulmonary
Hypertension
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases
Cardiovascular Diseases
Aspirin
Simvastatin
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Central Nervous System Agents
Anticholesteremic Agents
Hypolipidemic Agents

ClinicalTrials.gov processed this record on August 19, 2014