Platelet-Dependent Thrombosis: a Placebo-Controlled Trial of Antiplatelet Therapy (Clopidogrel)

Condition(s) targeted: Type 2 Diabetes Mellitus; Coronary Artery Disease

Intervention: clopidogrel (Drug); placebo (Drug)

Phase: Phase 4

Status: Not yet recruiting

Sponsored by: Newcastle-upon-Tyne Hospitals NHS Trust

Official(s) and/or principal investigator(s):
Azfar G Zaman, MD FRCP, Principal Investigator, Affiliation: Consultant cardiologist and Honoraray Lecturer

Overall contact:
Girish N Viswanathan, MRCP, Phone: +441912824210, Email: girish.viswanathan@newcastle.ac.uk

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.

Official title: 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

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

Primary outcome: To compare the effect of Clopidogrel in reduction of thrombogenicity in patients with T2DM and CAD with placebo

Secondary outcome:

To identify patients (in particular T2DM patients with CAD) resistant to oral antiplatelet therapy

To characterise features in T2DM patients responsible for increased thrombogenicity

Detailed description: 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.

Minimum age: 18 Years. Maximum age: 75 Years. Gender(s): Both.

Criteria:

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

Girish N Viswanathan, MRCP, Phone: +441912824210, Email: girish.viswanathan@newcastle.ac.uk

Newcastle Diabetes Centre, Newcastle General Hospital, Newcastle upon Tyne, Tyne and Wear NE4 6BE, United Kingdom

Freeman Hospital, Newcastle upon Tyne, Tyne and Wear NE77DN, United Kingdom

Related publications:

Osende JI, Badimon JJ, Fuster V, Herson P, Rabito P, Vidhun R, Zaman A, Rodriguez OJ, Lev EI, Rauch U, Heflt G, Fallon JT, Crandall JP. Blood thrombogenicity in type 2 diabetes mellitus patients is associated with glycemic control. J Am Coll Cardiol. 2001 Nov 1;38(5):1307-12.

Shechter M, Merz CN, Paul-Labrador MJ, Kaul S. Blood glucose and platelet-dependent thrombosis in patients with coronary artery disease. J Am Coll Cardiol. 2000 Feb;35(2):300-7.

Helft G, Osende JI, Worthley SG, Zaman AG, Rodriguez OJ, Lev EI, Farkouh ME, Fuster V, Badimon JJ, Chesebro JH. Acute antithrombotic effect of a front-loaded regimen of clopidogrel in patients with atherosclerosis on aspirin. Arterioscler Thromb Vasc Biol. 2000 Oct;20(10):2316-21.

Natarajan A, Zaman AG, Marshall SM. Platelet hyperactivity in type 2 diabetes: role of antiplatelet agents. Diab Vasc Dis Res. 2008 Jun;5(2):138-44.

Starting date: December 2008
Ending date: July 2011
Last updated: August 5, 2008