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

Sponsor:	Newcastle-upon-Tyne Hospitals NHS Trust
Collaborators:	British Heart Foundation University of Newcastle Upon-Tyne
Information provided by:	Newcastle-upon-Tyne Hospitals NHS Trust
ClinicalTrials.gov Identifier:	NCT00728156

Purpose

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.

Condition	Intervention	Phase
Type 2 Diabetes Mellitus Coronary Artery Disease	Drug: clopidogrel Drug: placebo	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
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

Resource links provided by NLM:

Genetics Home Reference related topics: 6q24-related transient neonatal diabetes mellitus

MedlinePlus related topics: Coronary Artery Disease Diabetes Diabetes Type 2

Drug Information available for: Clopidogrel Clopidogrel Bisulfate

U.S. FDA Resources

Further study details as provided by Newcastle-upon-Tyne Hospitals NHS Trust:

Primary Outcome Measures:

To compare the effect of Clopidogrel in reduction of thrombogenicity in patients with T2DM and CAD with placebo [ Time Frame: seven days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To identify patients (in particular T2DM patients with CAD) resistant to oral antiplatelet therapy [ Time Frame: seven days ] [ Designated as safety issue: No ]
To characterise features in T2DM patients responsible for increased thrombogenicity [ Time Frame: seven days ] [ Designated as safety issue: No ]

Estimated Enrollment:	90
Study Start Date:	August 2009
Estimated Study Completion Date:	July 2011
Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: C 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 75 milligrams, oral, clopidogrel, one tablet daily, for seven days after the baseline chamber study. Other Names: Plavix, 75 milligrams Sanofi Pharma Bristol-Myers Squibb SNC 174 Avenue de France F-75013 Paris - France EU/1/98/069/005a
Placebo Comparator: P 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 Placebo: Hydroxy methyl cellulose, similar in weight to the active medication 75 mgs, oral tablets, once a day

Arms

Assigned Interventions

Active Comparator: C

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

75 milligrams, oral, clopidogrel, one tablet daily, for seven days after the baseline chamber study.

Other Names:

Plavix, 75 milligrams
Sanofi Pharma Bristol-Myers Squibb SNC
174 Avenue de France
F-75013 Paris - France
EU/1/98/069/005a

Placebo Comparator: P

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

Placebo: Hydroxy methyl cellulose, similar in weight to the active medication 75 mgs, oral tablets, once a day

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

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00728156

Locations

United Kingdom
Newcastle Diabetes Centre, Newcastle General Hospital
Newcastle upon Tyne, Tyne and Wear, United Kingdom, NE4 6BE
Freeman Hospital
Newcastle upon Tyne, Tyne and Wear, United Kingdom, NE77DN

Sponsors and Collaborators

Newcastle-upon-Tyne Hospitals NHS Trust

British Heart Foundation

University of Newcastle Upon-Tyne

Investigators

Principal Investigator:

Azfar G Zaman, MD FRCP

Consultant cardiologist and Honoraray Lecturer

More Information

Publications:

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. Epub 2008 Oct 1. No abstract available.

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.

Responsible Party:	Dr Azfar G Zaman, Consultant Cardiologist and Honorary Senior Lecturer, Regional Cardiothoracic Centre, Freeeman Hospital
ClinicalTrials.gov Identifier:	NCT00728156 History of Changes
Other Study ID Numbers:	3639a, British Heart Foundation
Study First Received:	August 1, 2008
Last Updated:	July 21, 2011
Health Authority:	United Kingdom: Medicines and Healthcare Products Regulatory Agency; United Kingdom: National Health Service; United Kingdom: Research Ethics Committee

Keywords provided by Newcastle-upon-Tyne Hospitals NHS Trust:

Type 2 Diabetes mellitus
Coronary artery disease
Platelet dependent thrombogenicity

Aspirin
Clopidogrel
Badimon Chamber

Additional relevant MeSH terms:

Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Diabetes Mellitus
Diabetes Mellitus, Type 2
Thrombosis
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Embolism and Thrombosis

Clopidogrel
Ticlopidine
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Fibrinolytic Agents
Fibrin Modulating Agents

ClinicalTrials.gov processed this record on February 09, 2012