Platelet-dependent Thrombosis: a Placebo-controlled Trial of Antiplatelet Therapy (Clopidogrel)

Study Overview
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Brief Summary
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Patients with diabetes are more likely to develop furring of their coronary arteries and present with angina and heart attacks. Furthermore, after such an event, they have poorer outcomes (higher rates of death) and survivors are more likely to have recurring symptoms. Using a novel clotting chamber the investigators have shown that patients with diabetes are more likely to develop blood clots. This study will look at the role of different blood thinning medications in patients with diabetes. If successful, the investigators will provide evidence to conduct large clinical studies to look at the role of additional blood thinning medication in reducing heart attacks and strokes in patients with diabetes.

Detailed Description
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The objective of this study is to compare the effect of Clopidogrel on platelet dependent thrombosis in patients with T2DM and CAD with placebo. The Badimon chamber, an ex vivo arterial injury model is used for this purpose. This model simulates the in vivo situation of high shear arterial wall damage and helps to quantify thrombus which is the sum endpoint of all haemostatic abnormalities seen in vitro.

Official Title
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Assessment of Platelet-dependent Thrombosis by an ex Vivo Arterial Injury Model: a Placebo Controlled Trial of Clopidogrel as Antiplatelet Therapy in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease

Conditions
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Type 2 Diabetes Mellitus, Coronary Artery Disease

Intervention / Treatment
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* Drug: clopidogrel
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with T2DM and CAS as defined below: Clinical definitions T2DM: Diagnosed according to the WHO criteria [53]. CAD:Presence of any one of the following: Angina plus positive exercise tolerance test, enzyme and/or Q wave positive myocardial infarction, angiographic evidence ( >50% stenosis of one vessel), percutaneous or surgical coronary revascularisation. Aged between 18 and 75 Provided written consent for participation in the trial prior to any study-specific procedures or requirements. Exclusion Criteria: Contraindication to Clopidogrel Smoking (current smokers and patients who quit smoking less than six months) Malignancy(diagnosed or under investigation) Haematological disorders (Anaemia, malignancy, bleeding disorders) Women of child-bearing potential Use of corticosteroids/other antithrombotic agents(warfarin) Chronic liver disease (Cirrhosis, malignancy and patients with more than twice the upper limit of liver function tests) Unable to consent. Use of other investigational study drugs within 1 year prior to study entry Previous participation in this study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: C<br>Patients assigned to clopidogrel in addition to their standard care.(all patients will be on aspirin)We aim to study the effect of clopidogrel as dual antiplatelet therapy in patients with established coronary artery disease and type 2 diabetes. Ninety patients with type 2 diabetes and stable coronary artery disease has been randomly treated with clopidogrel or placebo (45 each) for one week in addition to their standard care (including aspirin,75 mg once daily). | Drug: clopidogrel<br>* 75 milligrams, oral, clopidogrel, one tablet daily, for seven days after the baseline chamber study.<br>* Other names: EU/1/98/069/005a;|
| Placebo Comparator: P<br>Patients assigned to placebo in addition to their standard care.(all patients will be on aspirin).This is a single-centre randomised double-blind placebo-controlled parallel design study, comparing efficacy of clopidogrel versus placebo in patients with T2DM and coronary artery disease. Ninety patients have completed the study. All patients were on their routine medications as per standard practice. After informed consent, participants were randomised to receive either clopidogrel 75mg daily or placebo for 7 days. | Drug: placebo<br>* Placebo: Hydroxy methyl cellulose, similar in weight to the active medication 75 mgs, oral tablets, once a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the effect of Clopidogrel in reduction of thrombogenicity in patients with T2DM and CAD with placebo |  | seven days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To identify patients (in particular T2DM patients with CAD) resistant to oral antiplatelet therapy |  | seven days | 
| To characterise features in T2DM patients responsible for increased thrombogenicity |  | seven days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 Diabetes mellitus, Coronary artery disease, Platelet dependent thrombogenicity, Aspirin, Clopidogrel, Badimon Chamber