Effect of Clopidogrel (Plavix) on Postoperative Bleeding in Patients Undergoing Coronary Artery Bypass Surgery.

Sponsor

Catharina Ziekenhuis Eindhoven (Other)

Overall Status

Completed

CT.gov ID

NCT00724880

Collaborator

(none)

135

Enrollment

Arms

Duration (Months)

Study Details

Study Description

Brief Summary

Running title: Effect of Clopidogrel on Postoperative Bleeding in Patients undergoing Coronary Artery Bypass Surgery
Title: Clopidogrel and bleeding in patients undergoing coronary artery bypass grafting. Is surgical delay necessary in patients using clopidogrel? And if so, which is the safety time interval when clopidogrel should be stopped before surgery in order to avoid bleeding and other related complications.
Background: By blockade of the platelet ADP receptor, clopidogrel inhibits the binding of fibrinogen to the platelet GPIIb/IIIa receptor complex, thereby preventing platelet aggregation from ADP stimulation. Some authors suggest that the platelet function is completely recovered in 7 days after stopping clopidogrel in healthy subjects. Other researches suggest full recovery of platelet function in 3 to 5 days.
Study objectives: To investigate if the interruption of the clopidogrel is necessary before CABG in order to prevent bleeding and other complications.

To trace the increased risk patients for postoperative bleeding and to individualize the therapy according to TEG measurements.

Design: A prospective, randomized mono- center study
Patients: Patients who are receiving elective or urgent CABG surgery and are pre-treated at least 5 days before surgery with clopidogrel
Primary endpoint: To determine if there are significant differences in blood loss, transfusions and rethoracotomies in the three selected groups of patients treated with clopidogrel To asses the predictive value of the TEG clot strength in postoperative bleeding in patients using Clopidogrel.
Secondary endpoints: Death, myocardial infarction, stroke, respiratory failure, renal failure requiring dialysis, mediastinitis,readmission rates within 30 days from discharge, and ICU and hospital lengths of stay
Risks: Using standard dose of aprotinin, we consider no increased risk in blood loss and other related complications for this three groups of patients.
Possible benefits: Reduction of time delay in operating patients under treatment with clopidogrel.

A more accurate time interval when clopidogrel should be stopped before surgery in order to eliminate the risk of bleeding and associated complications.

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease	Drug: Clopidogrel Drug: Clopidogrel Drug: Clopidogrel	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

135 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Effect of Clopidogrel (Plavix) on Postoperative Bleeding in Patients Undergoing Coronary Artery Bypass Surgery. A Prospective Randomized Controlled Study

Study Start Date :

Jun 1, 2006

Actual Primary Completion Date :

Nov 1, 2007

Actual Study Completion Date :

Dec 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Clopidogrel is stopped 5 days prior to surgery	Drug: Clopidogrel Clopidogrel is stopped 5 days prior to surgery Other Names: plavix
Experimental: 2 Clopidogrel is stopped 3 days prior to surgery	Drug: Clopidogrel Clopidogrel is stopped 3 days prior to surgery Other Names: plavix
Experimental: 3 Clopidogrel is stopped 0 days prior to surgery	Drug: Clopidogrel Clopidogrel is stopped 0 days prior to surgery Other Names: plavix

Arm

Intervention/Treatment

Experimental: 1

Clopidogrel is stopped 5 days prior to surgery

Drug: Clopidogrel

Clopidogrel is stopped 5 days prior to surgery

Other Names:

plavix

Experimental: 2

Clopidogrel is stopped 3 days prior to surgery

Drug: Clopidogrel

Clopidogrel is stopped 3 days prior to surgery

Other Names:

plavix

Experimental: 3

Clopidogrel is stopped 0 days prior to surgery

Drug: Clopidogrel

Clopidogrel is stopped 0 days prior to surgery

Other Names:

plavix

Outcome Measures

Primary Outcome Measures

The primary end point of this study is to determine if there are significant differences in blood loss, transfusions and rethoracotomies in the three selected groups of patients treated with clopidogrel [within 30 days (+/- 5 days) after surgery]
To asses the predictive value of the TEG clot strength in postoperative bleeding in patients using clopidogrel [within 30 days (+/- 5 days) after surgery]

Secondary Outcome Measures

death [within 30 days (+/- 5 days) after surgery]
myocardial infarction [within 30 days (+/- 5 days) after surgery]
stroke [within 30 days (+/- 5 days) after surgery]
respiratory failure [within 30 days (+/- 5 days) after surgery]
renal failure requiring dialysis [within 30 days (+/- 5 days) after surgery]
mediastinitis [within 30 days (+/- 5 days) after surgery]
wound infection [within 30 days (+/- 5 days) after surgery]
readmission rates within 30 days from discharge [within 30 days (+/- 5 days) after surgery]
ICU and hospital lengths of stay. [within 30 days (+/- 5 days) after surgery]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria:

Patients who are using clopidogrel at least 5 days before surgery with a dose of 75 mg clopidogrel without loading dose with or without concomitant use of aspirin.
Patients who received a loading dose of 300-600 mg clopidogrel 24 hours before CABG, with or without concomitant use of aspirin
Patients approved for elective or urgent CABG surgery

Exclusion criteria:

Patients who are concomitant using oral coumarin derivates, heparine derivates iv., dipiridamol or other anticoagulant treatment, 5 days before operation.
Patients with pre-existing bleeding disorders, thrombocytopenia
Patients who have renal insufficiency (creatinine >2.0 mg/dL) or chronic renal failure requiring dialysis
Patients in end stage heart failure
Patients who have evidence of significant hepatic disease including clinical signs or laboratory values of total bilirubin> 2.0 mg/dL, ALAT or ASAT> 3X upper limit of normal, or INR >2X upper limit of normal (not due to anticoagulation therapy)
Emergency bypass surgery when patients cant be random enrolled in one of the three groups
Concomitant valvular or other cardiac procedures
Re-operation (patients known with previous heart operations)
Off-pump CABG
Chronic alcoholism
Immediate post operative complications that in the opinion of the investigator can alter the further results of the trial (thromboembolism or ischemic CVA with use of anticoagulants, severe liver function disorders, sepsis, disseminated intravascular coagulation, adverse effects to blood products, etc)
Patients whom recently (3-6 months before screening) received PCI and continuation of clopidogrel till the day of operation is advisable (according to the advice of the cardiologist)
Patients who refuse to accept medically- indicated blood products
Pregnancy and breast feeding
Patients who received investigational drugs in the previous 30 days, or are currently participating in a study during which the administration of investigational drugs within one month is anticipated