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

Coronary Artery Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00728156
• Other study ID #: 3639a
• Secondary ID: British Heart Fo
• Status: Completed
• Phase: Phase 4
• First received: August 1, 2008
• Last updated: October 7, 2015
• Start date: August 2009
• Est. completion date: April 2012

Study information

• Verified date: October 2015
• Source: Newcastle-upon-Tyne Hospitals NHS Trust
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited Kingdom: National Health ServiceUnited Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: April 2012
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Myocardial Ischemia
• Type 2 Diabetes Mellitus

Intervention

Drug:
• clopidogrel
75 milligrams, oral, clopidogrel, one tablet daily, for seven days after the baseline chamber study.
• placebo
Placebo: Hydroxy methyl cellulose, similar in weight to the active medication 75 mgs, oral tablets, once a day

Locations

Country	Name	City	State
United Kingdom	Freeman Hospital	Newcastle upon Tyne	Tyne and Wear
United Kingdom	Newcastle Diabetes Centre, Newcastle General Hospital	Newcastle upon Tyne	Tyne and Wear

Sponsors (3)

Lead Sponsor	Collaborator
Newcastle-upon-Tyne Hospitals NHS Trust	British Heart Foundation, University of Newcastle Upon-Tyne

Country where clinical trial is conducted

United Kingdom, 

References & Publications (5)

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. — View 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. — View 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. Review. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To compare the effect of Clopidogrel in reduction of thrombogenicity in patients with T2DM and CAD with placebo		seven days	No
Secondary	To identify patients (in particular T2DM patients with CAD) resistant to oral antiplatelet therapy		seven days	No
Secondary	To characterise features in T2DM patients responsible for increased thrombogenicity		seven days	No