Hypertension, PulmonaryPhase 2NCT00384865
A Study of Aspirin and Simvastatin in Pulmonary Arterial Hypertension
A Phase 2 study testing Simvastatin and Aspirin in people with Hypertension, Pulmonary, run by University of Pennsylvania at 4 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hypertension, Pulmonary
- What is being tested?
- Simvastatin and Aspirin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 64 participants
- Where
- 4 sitesUnited States
- Study dates
- Sep 2006to Oct 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 28Show fewer
- 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
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Johns Hopkins University
Baltimore, Maryland, 21205
Tufts University School of Medicine
Boston, Massachusetts, 02110
Columbia University
New York, New York, 10032
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: 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).
Read the 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.
- Conditions
- Hypertension, Pulmonary
- Being tested
- Simvastatin, Aspirin, Placebo
- Keywords
- Pulmonary Arterial Hypertension
- Medical subject headings
- Hypertension, Pulmonary, Pulmonary Arterial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SimvastatinDrug
Also called Zocor
Simvastatin 40 mg, taken orally, once a day for 6 months
AspirinDrug
Also called acetylsalicylic acid
Aspirin 81 mg, taken orally, once a day for 6 months
PlaceboDrug
Placebo, taken orally, once a day for 6 months
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: 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 Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Distance Walked in Six Minutes
Measured: Measured at 6 months
Secondary outcomes (2)
Time to Clinical Worsening Events (Number of Events)
Defined by the addition of new PAH therapies or dose increases in previously stable PAH therapy, hospitalization for right-sided heart failure, lung transplantation, atrial septostomy, and cardiovascular and all-cause death.
Measured: Measured at 6 months
Adverse Events
Please refer to the Adverse Event Tables for specific information
Measured: Measured at 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2006 (estimated)
- Study startSep 2006
- Primary completionOct 2009
- Study completionOct 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Hypertension, PulmonaryStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor
- Investigators
- Steven M Kawut, MD, MS, Principal investigator, University of PennsylvaniaDavid J Lederer, MD, MS, Principal investigator, Columbia UniversityReda E Girgis, MB, BCh, Principal investigator, Johns Hopkins UniversityKari E Roberts, MD, Principal investigator, Tufts University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00384865
- Sponsor's protocol ID
- 458
- Other IDs
- R01HL082895-01
- Status last verified
- Jul 2017
- First submitted
- 30 Sep 2006
- Last updated
- 21 Jul 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 21593252Al-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.
PubMed 26501464Matura 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.
PubMed 25615959Kawut 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.
PubMed 21146637
Study at a glance
From the registry record, last updated by the sponsor on 21 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Clinical Trial of Aspirin and Simvastatin in Pulmonary Arterial Hypertension
- ClinicalTrials.gov ID
- NCT00384865
- Acronym / sponsor ID
- 458
- Conditions
- Hypertension, Pulmonary
- Keywords
- Pulmonary Arterial Hypertension
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 64 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Sep 2006
- Primary completion
- Oct 2009 (actual)
- Study completion
- Oct 2009 (actual)
- First posted
- 6 Oct 2006 (estimated)
- Results
- Posted 21 Jul 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether aspirin and simvastatin are safe and effective for the treatment of pulmonary arterial hypertension (PAH).
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Aspirin 81 mg + Simvastatin 40 mg | Active comparator | Drug: Simvastatin, Drug: AspirinSimvastatin: Simvastatin 40 mg, taken orally, once a day for 6 months Aspirin: Aspirin 81 mg, taken orally, once a day for 6 months |
| Aspirin 81 mg + Placebo | Active comparator | Drug: Aspirin, Drug: PlaceboAspirin: Aspirin 81 mg, taken orally, once a day for 6 months Placebo taken orally, once a day for 6 months |
| Placebo + Simvastatin 40 mg | Active comparator | Drug: Simvastatin, Drug: PlaceboPlacebo taken orally, once a day for 6 months Simvastatin: Simvastatin 40 mg, taken orally, once a day for 6 months |
| Placebo + Placebo | Placebo comparator | Drug: PlaceboPlacebo taken orally, once a day for 6 months Placebo taken orally, once a day for 6 months |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (28 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SimvastatinAlso: ZocorSimvastatin 40 mg, taken orally, once a day for 6 months | Drug | Aspirin 81 mg + Simvastatin 40 mg, Placebo + Simvastatin 40 mg |
| AspirinAlso: acetylsalicylic acidAspirin 81 mg, taken orally, once a day for 6 months | Drug | Aspirin 81 mg + Placebo, Aspirin 81 mg + Simvastatin 40 mg |
| PlaceboPlacebo, taken orally, once a day for 6 months | Drug | Aspirin 81 mg + Placebo, Placebo + Placebo, Placebo + Simvastatin 40 mg |
Primary outcome
Distance Walked in Six Minutes
Time frame: Measured at 6 months
2 secondary outcomes
Time to Clinical Worsening Events (Number of Events)
Time frame: Measured at 6 months
Adverse Events
Time frame: Measured at 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jul 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 21593252Kawut 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.
- Derived from this study: PubMed 26501464Al-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.
- Derived from this study: PubMed 25615959Matura 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.
- Derived from this study: PubMed 21146637Kawut 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steven M Kawut, MD, MS principal investigator
University of Pennsylvania
David J Lederer, MD, MS principal investigator
Columbia University
Reda E Girgis, MB, BCh principal investigator
Johns Hopkins University
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Simvastatin and Aspirin in people with Hypertension, Pulmonary, run by University of Pennsylvania at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Jul 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Distance Walked in Six Minutes (time frame: Measured at 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00384865, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jul 2017.