Safety and Efficacy of Prolonged Use of Bivalirudin 4 Hours After ePCI (COBER Study)
Primary Purpose
Coronary Heart Disease
Status
Completed
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
prolonged continuous use of bivalirudin
bivalirudin use during ePCI
Sponsored by
About this trial
This is an interventional prevention trial for Coronary Heart Disease focused on measuring bivalirudin, prolonged use, peri-operative myocardial injury, percutaneous coronary intervention
Eligibility Criteria
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
Sites / Locations
- Nanjing First Hospital, Nanjing Medical University
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Other
Arm Label
prolonged continuous use of bivalirudine
bivalirudin use during ePCI
Arm Description
A total of 165 patients are assigned to group with prolonged continuous use of bivalirudin after randomization schedule.
A total of 165 patients are assigned to group with bivalirudin use during ePCI after randomization schedule.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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
Full Information
NCT ID
NCT04120961
First Posted
September 29, 2019
Last Updated
August 8, 2022
Sponsor
Nanjing First Hospital, Nanjing Medical University
1. Study Identification
Unique Protocol Identification Number
NCT04120961
Brief Title
Safety and Efficacy of Prolonged Use of Bivalirudin 4 Hours After ePCI (COBER Study)
Official Title
Safety and Efficacy of Prolonged Use of Bivalirudin 4 Hours After Elective PCI in Patients With CHD (COBER Study)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
September 20, 2019 (Actual)
Primary Completion Date
August 1, 2022 (Actual)
Study Completion Date
August 1, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nanjing First Hospital, Nanjing Medical University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronary Heart Disease
Keywords
bivalirudin, prolonged use, peri-operative myocardial injury, percutaneous coronary intervention
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
330 (Actual)
8. Arms, Groups, and Interventions
Arm Title
prolonged continuous use of bivalirudine
Arm Type
Experimental
Arm Description
A total of 165 patients are assigned to group with prolonged continuous use of bivalirudin after randomization schedule.
Arm Title
bivalirudin use during ePCI
Arm Type
Other
Arm Description
A total of 165 patients are assigned to group with bivalirudin use during ePCI after randomization schedule.
Intervention Type
Drug
Intervention Name(s)
prolonged continuous use of bivalirudin
Other Intervention Name(s)
prolonged continuous use of bivalirudin 4 hours after elective PCI
Intervention Description
prolonged continuous use of bivalirudin 4 hours after elective PCI (dose: 0.75 mg/kg bolus plus 1.75 mg/kg per hour)
Intervention Type
Drug
Intervention Name(s)
bivalirudin use during ePCI
Other Intervention Name(s)
bivalirudin use during ePCI period
Intervention Description
bivalirudin use during ePCI (0.75 mg/kg bolus plus 1.75 mg/kg per hour)
Primary Outcome Measure Information:
Title
The incidence rate of PMI in CHD patients 3 days after ePCI
Description
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
Time Frame
Clinical follow up at 3 days after ePCI
Secondary Outcome Measure Information:
Title
The incidence rate of MACEs and bleeding
Description
The incidence rate of major adverse cardiac events and bleeding between prolonged use of bivalirudin and bivalirudin use during ePCI groups
Time Frame
Clinical follow up at 7 days after ePCI
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zhiming Wu, MD
Organizational Affiliation
Nanjing First Hospital, Nanjing Medical University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Nanjing First Hospital, Nanjing Medical University
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210006
Country
China
12. IPD Sharing Statement
Citations:
PubMed Identifier
25775052
Citation
Han Y, Guo J, Zheng Y, Zang H, Su X, Wang Y, Chen S, Jiang T, Yang P, Chen J, Jiang D, Jing Q, Liang Z, Liu H, Zhao X, Li J, Li Y, Xu B, Stone GW; BRIGHT Investigators. Bivalirudin vs heparin with or without tirofiban during primary percutaneous coronary intervention in acute myocardial infarction: the BRIGHT randomized clinical trial. JAMA. 2015 Apr 7;313(13):1336-46. doi: 10.1001/jama.2015.2323.
Results Reference
background
PubMed Identifier
12588269
Citation
Lincoff AM, Bittl JA, Harrington RA, Feit F, Kleiman NS, Jackman JD, Sarembock IJ, Cohen DJ, Spriggs D, Ebrahimi R, Keren G, Carr J, Cohen EA, Betriu A, Desmet W, Kereiakes DJ, Rutsch W, Wilcox RG, de Feyter PJ, Vahanian A, Topol EJ; REPLACE-2 Investigators. Bivalirudin and provisional glycoprotein IIb/IIIa blockade compared with heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary intervention: REPLACE-2 randomized trial. JAMA. 2003 Feb 19;289(7):853-63. doi: 10.1001/jama.289.7.853. Erratum In: JAMA. 2003 Apr 2;289(13):1638.
Results Reference
background
PubMed Identifier
20150324
Citation
Schulz S, Mehilli J, Ndrepepa G, Neumann FJ, Birkmeier KA, Kufner S, Richardt G, Berger PB, Schomig A, Kastrati A; Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT) 3 Trial Investigators. Bivalirudin vs. unfractionated heparin during percutaneous coronary interventions in patients with stable and unstable angina pectoris: 1-year results of the ISAR-REACT 3 trial. Eur Heart J. 2010 Mar;31(5):582-7. doi: 10.1093/eurheartj/ehq008. Epub 2010 Feb 11.
Results Reference
background
PubMed Identifier
21502650
Citation
Devereaux PJ, Xavier D, Pogue J, Guyatt G, Sigamani A, Garutti I, Leslie K, Rao-Melacini P, Chrolavicius S, Yang H, Macdonald C, Avezum A, Lanthier L, Hu W, Yusuf S; POISE (PeriOperative ISchemic Evaluation) Investigators. Characteristics and short-term prognosis of perioperative myocardial infarction in patients undergoing noncardiac surgery: a cohort study. Ann Intern Med. 2011 Apr 19;154(8):523-8. doi: 10.7326/0003-4819-154-8-201104190-00003.
Results Reference
background
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Safety and Efficacy of Prolonged Use of Bivalirudin 4 Hours After ePCI (COBER Study)
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