A Study of Aspirin and Simvastatin in Pulmonary Arterial Hypertension

NCT00384865 | Terminated Phase 2 Results DMC

• 2 other identifiers: 458R01HL082895-01
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 4

Brief Summary

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

Conditions

Hypertension, Pulmonary

Keywords

Pulmonary Arterial Hypertension

Outcome Measures

Primary Outcomes (1)

• Distance Walked in Six Minutes

  Measured at 6 months

Secondary Outcomes (2)

• Time to Clinical Worsening Events (Number of Events)

  Measured at 6 months

• Adverse Events

  Measured at 6 months

Study Arms (4)

Aspirin 81 mg + Simvastatin 40 mg

ACTIVE COMPARATOR

Simvastatin: Simvastatin 40 mg, taken orally, once a day for 6 months Aspirin: Aspirin 81 mg, taken orally, once a day for 6 months

Drug: Simvastatin; Drug: Aspirin

Aspirin 81 mg + Placebo

ACTIVE COMPARATOR

Aspirin: Aspirin 81 mg, taken orally, once a day for 6 months Placebo taken orally, once a day for 6 months

Drug: Aspirin; Drug: Placebo

Placebo + Simvastatin 40 mg

ACTIVE COMPARATOR

Placebo taken orally, once a day for 6 months Simvastatin: Simvastatin 40 mg, taken orally, once a day for 6 months

Drug: Simvastatin; Drug: Placebo

Placebo + Placebo

PLACEBO COMPARATOR

Placebo taken orally, once a day for 6 months Placebo taken orally, once a day for 6 months

Drug: Placebo

Interventions

Simvastatin DRUG

Simvastatin 40 mg, taken orally, once a day for 6 months

Also known as: Zocor

Aspirin 81 mg + Simvastatin 40 mg; Placebo + Simvastatin 40 mg

Aspirin DRUG

Aspirin 81 mg, taken orally, once a day for 6 months

Also known as: acetylsalicylic acid

Aspirin 81 mg + Placebo; Aspirin 81 mg + Simvastatin 40 mg

Placebo DRUG

Placebo, taken orally, once a day for 6 months

Aspirin 81 mg + Placebo; Placebo + Placebo; Placebo + Simvastatin 40 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Pennsylvania: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (4)

Johns Hopkins University

Baltimore, Maryland, 21205, United States

Location

Tufts University School of Medicine

Boston, Massachusetts, 02110, United States

Location

Columbia University

New York, New York, 10032, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (4)

• Kawut SM, Bagiella E, Lederer DJ, Shimbo D, Horn EM, Roberts KE, Hill NS, Barr RG, Rosenzweig EB, Post W, Tracy RP, Palevsky HI, Hassoun PM, Girgis RE; ASA-STAT Study Group. Randomized clinical trial of aspirin and simvastatin for pulmonary arterial hypertension: ASA-STAT. Circulation. 2011 Jun 28;123(25):2985-93. doi: 10.1161/CIRCULATIONAHA.110.015693. Epub 2011 May 18.

  PMID: 21593252 RESULT

• Al-Naamani N, Palevsky HI, Lederer DJ, Horn EM, Mathai SC, Roberts KE, Tracy RP, Hassoun PM, Girgis RE, Shimbo D, Post WS, Kawut SM; ASA-STAT Study Group. Prognostic Significance of Biomarkers in Pulmonary Arterial Hypertension. Ann Am Thorac Soc. 2016 Jan;13(1):25-30. doi: 10.1513/AnnalsATS.201508-543OC.

  PMID: 26501464 DERIVED

• Matura LA, Ventetuolo CE, Palevsky HI, Lederer DJ, Horn EM, Mathai SC, Pinder D, Archer-Chicko C, Bagiella E, Roberts KE, Tracy RP, Hassoun PM, Girgis RE, Kawut SM. Interleukin-6 and tumor necrosis factor-alpha are associated with quality of life-related symptoms in pulmonary arterial hypertension. Ann Am Thorac Soc. 2015 Mar;12(3):370-5. doi: 10.1513/AnnalsATS.201410-463OC.

  PMID: 25615959 DERIVED

• Kawut SM, Bagiella E, Shimbo D, Lederer DJ, Al-Naamani N, Roberts KE, Barr RG, Post W, Horn EM, Tracy R, Hassoun P, Girgis R; ASA-STAT Study Group. Rationale and design of a phase II clinical trial of aspirin and simvastatin for the treatment of pulmonary arterial hypertension: ASA-STAT. Contemp Clin Trials. 2011 Mar;32(2):280-7. doi: 10.1016/j.cct.2010.12.005. Epub 2010 Dec 10.

  PMID: 21146637 DERIVED

MeSH Terms

Conditions

Hypertension, Pulmonary; Pulmonary Arterial Hypertension

Interventions

Simvastatin; Aspirin

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives

Limitations and Caveats

* The primary end point that should be used in early-stage clinical trials in PAH is uncertain. * We did not include invasive hemodynamic end points. * Early termination led to missing data for those active subjects in the trial at termination (n16).

Results Point of Contact

• Title: Steven Kawut
• Organization: Penn

kawut@upenn.edu

215-573-0258

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2006
• First Posted: October 6, 2006
• Study Start: September 1, 2006
• Primary Completion: October 1, 2009
• Study Completion: October 1, 2009
• Last Updated: July 21, 2017
• Results First Posted: July 21, 2017

Record last verified: 2017-07

Locations

US (4)