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

Study Overview
=================
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.

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

Conditions
-----------------
Coronary Artery Disease

Intervention / Treatment
-----------------
* Drug: Clopidogrel
* Drug: Clopidogrel
* Drug: Clopidogrel


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Clopidogrel is stopped 5 days prior to surgery | Drug: Clopidogrel<br>* Clopidogrel is stopped 5 days prior to surgery<br>* Other names: plavix;|
| Experimental: 2<br>Clopidogrel is stopped 3 days prior to surgery | Drug: Clopidogrel<br>* Clopidogrel is stopped 3 days prior to surgery<br>* Other names: plavix;|
| Experimental: 3<br>Clopidogrel is stopped 0 days prior to surgery | Drug: Clopidogrel<br>* Clopidogrel is stopped 0 days prior to surgery<br>* Other names: plavix;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
coronary artery bypass grafting, clopidogrel, post-operative bleeding