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

Coronary Heart Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04120961
• Other study ID #: KY20190823-05
• Status: Completed
• Phase: N/A
• Start date: September 20, 2019
• Est. completion date: August 1, 2022

Study information

• Verified date: August 2022
• Source: Nanjing First Hospital, Nanjing Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 330
• Est. completion date: August 1, 2022
• Est. primary completion date: August 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Coronary Heart Disease
• Heart Diseases
• Myocardial Ischemia

Intervention

Drug:
• prolonged continuous use of bivalirudin
prolonged continuous use of bivalirudin 4 hours after elective PCI (dose: 0.75 mg/kg bolus plus 1.75 mg/kg per hour)
• bivalirudin use during ePCI
bivalirudin use during ePCI (0.75 mg/kg bolus plus 1.75 mg/kg per hour)

Locations

Country	Name	City	State
China	Nanjing First Hospital, Nanjing Medical University	Nanjing	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
Nanjing First Hospital, Nanjing Medical University

Country where clinical trial is conducted

China, 

References & Publications (4)

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. — View 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. — View 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. Erratum in: JAMA. 2003 Apr 2;289(13):1638. — View Citation

Schulz S, Mehilli J, Ndrepepa G, Neumann FJ, Birkmeier KA, Kufner S, Richardt G, Berger PB, Schömig 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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