Clinical trial NCT00728156: Platelet-dependent Thrombosis: a Placebo-controlled Trial of Antiplatelet Therapy (Clopidogrel)
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetes Mellitus
Coronary Artery Disease
Keywords: Type 2 Diabetes mellitus
Coronary artery disease
Platelet dependent thrombogenicity
Aspirin
Clopidogrel
Badimon Chamber
Lead sponsor: Newcastle-upon-Tyne Hospitals NHS Trust
Sponsor class: OTHER
Collaborators: name: British Heart Foundation
name: University of Newcastle Upon-Tyne
First posted: 2008-08-05
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility 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

Primary outcomes:
measure: To compare the effect of Clopidogrel in reduction of thrombogenicity in patients with T2DM and CAD with placebo
timeFrame: seven days
Secondary outcomes:
measure: To identify patients (in particular T2DM patients with CAD) resistant to oral antiplatelet therapy
timeFrame: seven days
measure: To characterise features in T2DM patients responsible for increased thrombogenicity
timeFrame: seven days
Other outcomes:
Locations:
city: Newcastle upon Tyne
country: United Kingdom
facility: Newcastle Diabetes Centre, Newcastle General Hospital
state: Tyne and Wear
city: Newcastle upon Tyne
country: United Kingdom
facility: Freeman Hospital
state: Tyne and Wear
Study officials:
affiliation: Consultant cardiologist and Honoraray Lecturer
name: Azfar G Zaman, MD FRCP
role: PRINCIPAL_INVESTIGATOR
References:
citation: Natarajan A, Marshall SM, Worthley SG, Badimon JJ, Zaman AG. The presence of coronary artery disease increases platelet-dependent thrombosis in patients with type 2 diabetes mellitus. J Thromb Haemost. 2008 Dec;6(12):2210-3. doi: 10.1111/j.1538-7836.2008.03176.x. Epub 2008 Oct 1. No abstract available.
citation: 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. doi: 10.1016/s0735-1097(01)01555-8.
citation: 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. doi: 10.1016/s0735-1097(99)00545-8.
citation: 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. doi: 10.1161/01.atv.20.10.2316.
citation: 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. doi: 10.3132/dvdr.2008.023.