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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

September 30, 2006
January 31, 2013
September 2006
October 2009   (final data collection date for primary outcome measure)
Distance walked in six minutes [ Time Frame: Measured at 6 months ] [ Designated as safety issue: No ]
Distance walked in six minutes (measured at Month 7)
Complete list of historical versions of study NCT00384865 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Platelet markers
  • Endothelial function
  • World Health Organization (WHO) functional class
  • Use of PAH medication
  • Time to clinical events
  • Adverse events (all measured at Month 7)
Not Provided
Not Provided
 
A Study of Aspirin and Simvastatin in Pulmonary Arterial Hypertension
A Clinical Trial of Aspirin and Simvastatin in Pulmonary Arterial Hypertension

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

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Hypertension, Pulmonary
  • 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
  • Drug: Placebo
    Placebo, taken orally, once a day for 6 months
  • Active Comparator: 1
    Aspirin 81 mg + Simvastatin 40 mg
    Interventions:
    • Drug: Simvastatin
    • Drug: Aspirin
  • Active Comparator: 2
    Aspirin 81 mg + Placebo
    Interventions:
    • Drug: Aspirin
    • Drug: Placebo
  • Active Comparator: 3
    Placebo + Simvastatin 40 mg
    Interventions:
    • Drug: Simvastatin
    • Drug: Placebo
  • Placebo Comparator: 4
    Placebo + Placebo
    Intervention: Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
64
October 2009
October 2009   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00384865
458, R01HL082895-01
Yes
University of Pennsylvania
University of Pennsylvania
National Heart, Lung, and Blood Institute (NHLBI)
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
University of Pennsylvania
July 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP