Diabetes MellitusPhase 4RATIONALNCT00793754
Aspirin Statins Or Both For The Reduction Of Thrombin Generation In Diabetic People
A Phase 4 study testing Aspirin, Atorvastatin and Aspirin + Atorvastatin in people with Diabetes Mellitus, run by Fundacion GESICA at 1 site in Argentina.
Trial summary
Despite formal recommendations, evidence of efficacy of aspirin in individuals with diabetes is scant and controversial. While the efficacy of aspirin versus placebo in patients with diabetes is currently under investigation in big randomized controlled trials, the putative additive effects of aspirin and statins in… Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Diabetes Mellitus
- What is being tested?
- Aspirin, Atorvastatin and Aspirin + Atorvastatin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteArgentina
- Study dates
- Mar 2009to Oct 2011
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diabetes mellitus treated with insulin or orl agents
- At least 50 years old
Who cannot join
- Previous cardiovascular events
- current or past (within last 30 days) treatment with aspirin
- current or past (within last 180 days) treatment with statins
Trial locations and contacts
1 site in 1 country.
Argentina1 site
Centro de Educación Médica e Investigaciones Clínicas (CEMIC)
Buenos Aires
About this study
Despite formal recommendations, evidence of efficacy of aspirin in individuals with diabetes is scant and controversial. While the efficacy of aspirin versus placebo in patients with diabetes is currently under investigation in big randomized controlled trials, the putative additive effects of aspirin and statins in this population remain to be investigated. Moreover there are no data examining the pathophysiologic means by which aspirin with or without statins affects thrombosis in diabetic patients.
The aim of this trial is to evaluate the efficacy of low-dose aspirin (100 mg/daily), statins, both or neither for the reduction of thrombin generation. These preventive strategies will be evaluated on the top of the other strategies aimed at optimizing the care of diabetic patients in terms of metabolic control and control of the other cardiovascular risk factors.
Read the detailed description
Despite the very high cardiovascular risk profile, evidence of efficacy of aspirin in individuals with diabetes is scant.
The meta-analysis on the efficacy of antiplatelet therapy involving a total of about 5,000 diabetic subjects indicates a non significant reduction in the risk of major cardiovascular events of 7%, compared with a reduction of 25% documented in secondary prevention studies.
Diabetes could represent a special case of aspirin resistance, although no specific studies have, to our knowledge, fully explored this hypothesis. The poor platelet responsiveness to aspirin has been recently proposed as a possible explanation of the failure of antiplatelet therapy to prevent cardiovascular events. The reduction in the aspirin activity in some patients is indicated by the failure in adequately suppressing thromboxane-A2 synthesis, as documented by the presence of high levels of its urinary metabolites.
The substantial lack of clear evidence is reflected by the low use of this drug in clinical practice; in fact, only 10% of diabetic patients are treated with aspirin for the prevention of cardiovascular events.
On the other hand, statins provide a similar efficacy for the prevention of major cardiovascular events in populations with and without diabetes.
It has been recently shown that platelet response to aspirin is linearly reduced with increasing cholesterol plasma levels. The presence of dyslipidemia, particularly common among diabetic patients, could thus be at least partially responsible for a lower efficacy of aspirin in this population. The concomitant use of statins could thus restore the normal platelet sensitivity to aspirin by reducing cholesterol levels
One additional reason to hypothesize a positive effect of statins in improving platelet response to aspirin is related to their anti-inflammatory properties
While the efficacy of aspirin versus placebo in patients with diabetes is currently under investigation, the additive effects of aspirin and statins in this population remain to be investigated. This aspect is of particular interest in the light of the existing debate regarding the need of multiple interventions to reduce total cardiovascular risk.
Given these premises, it is important to evaluate the effectiveness of aspirin use in primary prevention of cardiovascular events in association with statins therapy when included in a strategy of global risk control.
The RATIONAL Study will evaluate whether the combined use of aspirin (100 mg d) and statins (Atorvastatin 40 mg daily) is superior to the use of these single agents for the reduction of thrombin generation in patients with diabetes and without previous cardiovascular events.
- Conditions
- Diabetes Mellitus
- Being tested
- Aspirin, Atorvastatin, Aspirin + Atorvastatin
- Medical subject headings
- Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AspirinDrug
100 mg / day for 8 weeks
AtorvastatinDrug
40 mg / day for 8 weeks
Aspirin + AtorvastatinDrug
Aspirin 100 mg / day + Atorvastatin 40 mg / day for 8 weeks
| Study group | Role | What they receive |
|---|---|---|
| 1 | No intervention | Not described |
| 2 | Experimental | Aspirin 100 mg / day Receives: Drug: Aspirin |
| 3 | Experimental | Atorvastatin 40 mg / day Receives: Drug: Atorvastatin |
| 4 | Experimental | Aspirin 100 mg / day + Atorvastatin 40 mg / day Receives: Drug: Aspirin + Atorvastatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Thrombin generation
Measured: 8 weeks
Secondary outcomes (1)
C-reactive protein
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2008 (estimated)
- Study startMar 2009
- Primary completionOct 2011
- Study completionOct 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetes MellitusStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundacion GESICA
- Sponsor type
- University, hospital or other
- Investigators
- Alejandro Macchia, MD, Principal investigator, Fundacion GESICAHernan Doval, MD, Principal investigator, Fundacion GESICAJuan J Fuselli, MD, Principal investigator, Centro de Educación Medica e Investigaciones Clínicas Norberto QuirnoPablo D Comignani, MD, Principal investigator, Hospital Aleman
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00793754
- Sponsor's protocol ID
- 002
- Acronym
- RATIONAL
- Status last verified
- Oct 2011
- First submitted
- 18 Nov 2008
- Last updated
- 26 Oct 2011
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Macchia A, Laffaye N, Comignani PD, Cornejo Pucci E, Igarzabal C, Scazziota AS, Herrera L, Mariani JA, Bragagnolo JC, Catalano H, Tognoni G, Nicolucci A. Statins but not aspirin reduce thrombotic risk assessed by thrombin generation in diabetic patients without cardiovascular events: the RATIONAL trial. PLoS One. 2012;7(3):e32894. doi: 10.1371/journal.pone.0032894. Epub 2012 Mar 28.
PubMed 22470429
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Aspirin Statins Or Both For The Reduction Of Thrombin Generation In Diabetic People
- ClinicalTrials.gov ID
- NCT00793754
- Acronym / sponsor ID
- RATIONAL / 002
- Conditions
- Diabetes Mellitus
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Fundacion GESICAUniversity, hospital or other
- Study start
- Mar 2009
- Primary completion
- Oct 2011 (actual)
- Study completion
- Oct 2011 (actual)
- First posted
- 19 Nov 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Despite formal recommendations, evidence of efficacy of aspirin in individuals with diabetes is scant and controversial. While the efficacy of aspirin versus placebo in patients with diabetes is currently under investigation in big randomized controlled trials, the putative additive effects of aspirin and statins in this population remain to be investigated. Moreover there are no data examining the pathophysiologic means by which aspirin with or without statins affects thrombosis in diabetic patients.
The aim of this trial is to evaluate the efficacy of low-dose aspirin (100 mg/daily), statins, both or neither for the reduction of thrombin generation. These preventive strategies will be evaluated on the top of the other strategies aimed at optimizing the care of diabetic patients in terms of metabolic control and control of the other cardiovascular risk factors.
Detailed description
Despite the very high cardiovascular risk profile, evidence of efficacy of aspirin in individuals with diabetes is scant.
The meta-analysis on the efficacy of antiplatelet therapy involving a total of about 5,000 diabetic subjects indicates a non significant reduction in the risk of major cardiovascular events of 7%, compared with a reduction of 25% documented in secondary prevention studies.
Diabetes could represent a special case of aspirin resistance, although no specific studies have, to our knowledge, fully explored this hypothesis. The poor platelet responsiveness to aspirin has been recently proposed as a possible explanation of the failure of antiplatelet therapy to prevent cardiovascular events. The reduction in the aspirin activity in some patients is indicated by the failure in adequately suppressing thromboxane-A2 synthesis, as documented by the presence of high levels of its urinary metabolites.
The substantial lack of clear evidence is reflected by the low use of this drug in clinical practice; in fact, only 10% of diabetic patients are treated with aspirin for the prevention of cardiovascular events.
On the other hand, statins provide a similar efficacy for the prevention of major cardiovascular events in populations with and without diabetes.
It has been recently shown that platelet response to aspirin is linearly reduced with increasing cholesterol plasma levels. The presence of dyslipidemia, particularly common among diabetic patients, could thus be at least partially responsible for a lower efficacy of aspirin in this population. The concomitant use of statins could thus restore the normal platelet sensitivity to aspirin by reducing cholesterol levels
One additional reason to hypothesize a positive effect of statins in improving platelet response to aspirin is related to their anti-inflammatory properties
While the efficacy of aspirin versus placebo in patients with diabetes is currently under investigation, the additive effects of aspirin and statins in this population remain to be investigated. This aspect is of particular interest in the light of the existing debate regarding the need of multiple interventions to reduce total cardiovascular risk.
Given these premises, it is important to evaluate the effectiveness of aspirin use in primary prevention of cardiovascular events in association with statins therapy when included in a strategy of global risk control.
The RATIONAL Study will evaluate whether the combined use of aspirin (100 mg d) and statins (Atorvastatin 40 mg daily) is superior to the use of these single agents for the reduction of thrombin generation in patients with diabetes and without previous cardiovascular events.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1 | No intervention | – |
| 2 | Experimental | Drug: AspirinAspirin 100 mg / day |
| 3 | Experimental | Drug: AtorvastatinAtorvastatin 40 mg / day |
| 4 | Experimental | Drug: Aspirin + AtorvastatinAspirin 100 mg / day + Atorvastatin 40 mg / day |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Diabetes mellitus treated with insulin or orl agents
- At least 50 years old
Key exclusion criteria (3 listed)
- Previous cardiovascular events
- current or past (within last 30 days) treatment with aspirin
- current or past (within last 180 days) treatment with statins
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 |
|---|---|---|
| Aspirin100 mg / day for 8 weeks | Drug | 2 |
| Atorvastatin40 mg / day for 8 weeks | Drug | 3 |
| Aspirin + AtorvastatinAspirin 100 mg / day + Atorvastatin 40 mg / day for 8 weeks | Drug | 4 |
Primary outcome
Thrombin generation
Time frame: 8 weeks
1 secondary outcome
C-reactive protein
Time frame: 8 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2011.
- Derived from this study: PubMed 22470429Macchia A, Laffaye N, Comignani PD, Cornejo Pucci E, Igarzabal C, Scazziota AS, Herrera L, Mariani JA, Bragagnolo JC, Catalano H, Tognoni G, Nicolucci A. Statins but not aspirin reduce thrombotic risk assessed by thrombin generation in diabetic patients without cardiovascular events: the RATIONAL trial. PLoS One. 2012;7(3):e32894. doi: 10.1371/journal.pone.0032894. Epub 2012 Mar 28.
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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.
Alejandro Macchia, MD principal investigator
Fundacion GESICA
Hernan Doval, MD principal investigator
Fundacion GESICA
Juan J Fuselli, MD principal investigator
Centro de Educación Medica e Investigaciones Clínicas Norberto Quirno
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Aspirin, Atorvastatin and Aspirin + Atorvastatin in people with Diabetes Mellitus, run by Fundacion GESICA at 1 site in Argentina.
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 2 inclusion and 3 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: finished, as of the sponsor's last update on 26 Oct 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Argentina. 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Thrombin generation (time frame: 8 weeks). 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 NCT00793754, which also lists 1 linked publication.
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 26 Oct 2011.