Safety and Efficacy of Prolonged Use of Bivalirudin 4 Hours After ePCI (COBER Study)

Study Overview
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Brief Summary
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Since the development of percutaneous coronary intervention (PCI) in patients with coronary heart disease (CHD), unfractionated heparin (UFH) and low molecular weight heparin (LWMH) have been the preferred anticoagulants in peri-operative period. However, UFH has some defects, such as incomplete and unstable inhibition of thrombin, large individual differences, multiple monitoring of activated coagulation time (ACT), ineffective thrombin binding to fibrin, non-specific protein binding and induced thrombocytopenia (HIT). Compared with UFH, LWMH has lower non-specific protein binding rate, but it is not superior to UFH in efficacy, hemorrhage and HIT. Bivalirudin can bind specifically to thrombin catalytic site and anionic external binding site, directly inhibit thrombin activity, thereby inhibiting thrombin-catalyzed and induced reactions. At the same time, thrombin can also inactivate it by enzymatic hydrolysis of bivalirudin. Therefore, the inhibition of bivalirudin on thrombin is reversible and transient, and the risk of bleeding after drug withdrawal is relative small. It has been reported that bivalirudin can significantly reduce the risk of peri-operative bleeding during PCI period compared with UFH. Clopidogrel had not yet played a role in most patients after emergency PCI, and there was a blank period for 2-4 hours without effective antithrombotic concentration, which was also the peak period of acute stent thrombosis. Han and coworkers have shown that for acute myocardial infarction (AMI) patients undergoing emergency PCI, whether or not glycoprotein IIb/IIIa inhibitors were added, prolonged peri-operative use of bivalrudin was significantly better than UFH in terms of net clinical adverse event. However, for patients with elective PCI (ePCI), prolonged bivalirudin use was only used in some patients in REPLACE-2 and ISAR-REACT-3 studies, and the prolonged time of bivalrudin use after ePCI was not definite. Therefore, in the current study we aim to explore the efficacy and safety of prolonged bivalirudin use 4 hours after elective PCI in patients with CHD.

Detailed Description
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The current study is designed as a single-center, randomized and prospective study aiming to evaluate the safety and efficacy of prolonged continuous use of bivalirudin 4 hours after ePCI for the treatment of peri-operative myocardial injury (PMI) compared with the bivalirudin use during ePCI. Based on previous study reported and estimated 10% loss follow-up of these patients in each arm, a total of 330 patients with CHD were required in our study, and with 165 patients per group as a ratio of 1:1 randomization.

Official Title
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Safety and Efficacy of Prolonged Use of Bivalirudin 4 Hours After Elective PCI in Patients With CHD (COBER Study)

Conditions
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Coronary Heart Disease

Intervention / Treatment
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* Drug: prolonged continuous use of bivalirudin
* Drug: bivalirudin use during ePCI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: De novo lesions elective PCI Only single coronary artery treated at this time Exclusion Criteria: Those who meet the diagnostic criteria of acute myocardial infarction Patients with cardio-genic shock Patients with multiple organ failure Patients allergic to contrast Patients who can not tolerate dual antiplatelet therapy Patients who can't tolerate anticoagulation Recently infected patients Patients with hepatorenal dysfunction Thrombotic lesion of coronary artery Chronic total coronary occlusion lesion Patients with complex coronary bifurcation requiring two stent strategy Severe coronary calcified lesion Patients with percutaneous coronary angioplasty Patients with directional coronary atherectomy or rotational atherectomy Patients with drug coated balloon treatment Patients with bioabsorbable vascular scaffold implantation Previous percutaneous coronary intervention Previous coronary artery bypass graft Patients with active stage of autoimmune disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: prolonged continuous use of bivalirudine<br>A total of 165 patients are assigned to group with prolonged continuous use of bivalirudin after randomization schedule. | Drug: prolonged continuous use of bivalirudin<br>* prolonged continuous use of bivalirudin 4 hours after elective PCI (dose: 0.75 mg/kg bolus plus 1.75 mg/kg per hour)<br>* Other names: prolonged continuous use of bivalirudin 4 hours after elective PCI;|
| Other: bivalirudin use during ePCI<br>A total of 165 patients are assigned to group with bivalirudin use during ePCI after randomization schedule. | Drug: bivalirudin use during ePCI<br>* bivalirudin use during ePCI (0.75 mg/kg bolus plus 1.75 mg/kg per hour)<br>* Other names: bivalirudin use during ePCI period;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence rate of PMI in CHD patients 3 days after ePCI | the incidence rate of PMI indicated by the changes of myocardial injury biomarkers (such as TNI and CK-MB) in CHD patients between prolonged use of bivalirudin and bivalirudin use during ePCI groups | Clinical follow up at 3 days after ePCI | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence rate of MACEs and bleeding | The incidence rate of major adverse cardiac events and bleeding between prolonged use of bivalirudin and bivalirudin use during ePCI groups | Clinical follow up at 7 days after ePCI | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bivalirudin, prolonged use, peri-operative myocardial injury, percutaneous coronary intervention