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

NCT00728156 | Completed Phase 4 DMC

• 2 other identifiers: 3639aBritish Heart Foundation
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 2

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.

Conditions

Type 2 Diabetes Mellitus; Coronary Artery Disease

Keywords

Type 2 Diabetes mellitus; Coronary artery disease; Platelet dependent thrombogenicity; Aspirin; Clopidogrel; Badimon Chamber

Outcome Measures

Primary Outcomes (1)

• To compare the effect of Clopidogrel in reduction of thrombogenicity in patients with T2DM and CAD with placebo

  seven days

Secondary Outcomes (2)

• 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

Study Arms (2)

C

ACTIVE COMPARATOR

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

P

PLACEBO COMPARATOR

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

Interventions

clopidogrel DRUG

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

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

C

placebo DRUG

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

P

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Newcastle-upon-Tyne Hospitals NHS Trust: lead
• British Heart Foundation: collaborator
• University of Newcastle Upon-Tyne: collaborator

Study Sites (2)

Newcastle Diabetes Centre, Newcastle General Hospital

Newcastle upon Tyne, Tyne and Wear, NE4 6BE, United Kingdom

Location

Freeman Hospital

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

Location

Related Publications (5)

• 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.

  PMID: 18983525 BACKGROUND

• 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.

  PMID: 11691500 BACKGROUND

• 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.

  PMID: 10676673 BACKGROUND

• 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.

  PMID: 11031221 BACKGROUND

• 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.

  PMID: 18537103 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Coronary Artery Disease

Interventions

Clopidogrel

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Azfar G Zaman, MD FRCP

  Consultant cardiologist and Honoraray Lecturer

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 1, 2008
• First Posted: August 5, 2008
• Study Start: August 1, 2009
• Primary Completion: December 1, 2010
• Study Completion: April 1, 2012
• Last Updated: October 12, 2015

Record last verified: 2015-10

Locations

GB (2)