Aspirin Statins Or Both For The Reduction Of Thrombin Generation In Diabetic People

NCT ID: NCT00793754

Last Updated: 2011-10-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-03-31

Study Completion Date

2011-10-31

Brief Summary

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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

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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

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Diabetes Mellitus

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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1

Group Type NO_INTERVENTION

No interventions assigned to this group

2

Aspirin 100 mg / day

Group Type EXPERIMENTAL

Aspirin

Intervention Type DRUG

100 mg / day for 8 weeks

3

Atorvastatin 40 mg / day

Group Type EXPERIMENTAL

Atorvastatin

Intervention Type DRUG

40 mg / day for 8 weeks

4

Aspirin 100 mg / day + Atorvastatin 40 mg / day

Group Type EXPERIMENTAL

Aspirin + Atorvastatin

Intervention Type DRUG

Aspirin 100 mg / day + Atorvastatin 40 mg / day for 8 weeks

Interventions

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Aspirin

100 mg / day for 8 weeks

Intervention Type DRUG

Atorvastatin

40 mg / day for 8 weeks

Intervention Type DRUG

Aspirin + Atorvastatin

Aspirin 100 mg / day + Atorvastatin 40 mg / day for 8 weeks

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Diabetes mellitus treated with insulin or orl agents
* At least 50 years old

Exclusion Criteria

* Previous cardiovascular events
* current or past (within last 30 days) treatment with aspirin
* current or past (within last 180 days) treatment with statins
Minimum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fundacion GESICA

OTHER

Sponsor Role lead

Responsible Party

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Fundacion GESICA

Principal Investigators

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Alejandro Macchia, MD

Role: PRINCIPAL_INVESTIGATOR

Fundacion GESICA

Hernan Doval, MD

Role: PRINCIPAL_INVESTIGATOR

Fundacion GESICA

Juan J Fuselli, MD

Role: PRINCIPAL_INVESTIGATOR

Centro de Educación Medica e Investigaciones Clínicas Norberto Quirno

Pablo D Comignani, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Aleman

Locations

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Centro de Educación Médica e Investigaciones Clínicas (CEMIC)

Buenos Aires, , Argentina

Site Status

Countries

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Argentina

References

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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.

Reference Type DERIVED
PMID: 22470429 (View on PubMed)

Other Identifiers

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002

Identifier Type: -

Identifier Source: org_study_id