Coronary Heart DiseaseNCT04120961
Safety and Efficacy of Prolonged Use of Bivalirudin 4 Hours After ePCI (COBER Study)
A study testing prolonged continuous use of bivalirudin and bivalirudin use during ePCI in people with Coronary Heart Disease, run by Nanjing First Hospital, Nanjing Medical University at 1 site in China.
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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Coronary Heart Disease
- What is being tested?
- prolonged continuous use of bivalirudin and bivalirudin use during ePCI
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 330 participants
- Where
- 1 siteChina
- Study dates
- 20 Sep 2019to 1 Aug 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- De novo lesions
- elective PCI
- Only single coronary artery treated at this time
Who cannot join
- 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
Show all 19Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
China1 site
Nanjing First Hospital, Nanjing Medical University
Nanjing, Jiangsu, 210006
About this study
Official title: Safety and Efficacy of Prolonged Use of Bivalirudin 4 Hours After Elective PCI in Patients With CHD (COBER Study)
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.
Read the 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.
- Conditions
- Coronary Heart Disease
- Being tested
- prolonged continuous use of bivalirudin, bivalirudin use during ePCI
- Keywords
- bivalirudin, prolonged use, peri-operative myocardial injury, percutaneous coronary intervention
- Medical subject headings
- Coronary Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
prolonged continuous use of bivalirudinDrug
Also called prolonged continuous use of bivalirudin 4 hours after elective PCI
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 ePCIDrug
Also called bivalirudin use during ePCI period
bivalirudin use during ePCI (0.75 mg/kg bolus plus 1.75 mg/kg per hour)
| Study group | Role | What they receive |
|---|---|---|
| prolonged continuous use of bivalirudine | Experimental | A total of 165 patients are assigned to group with prolonged continuous use of bivalirudin after randomization schedule. Receives: Drug: prolonged continuous use of bivalirudin |
| bivalirudin use during ePCI | Other | A total of 165 patients are assigned to group with bivalirudin use during ePCI after randomization schedule. Receives: Drug: bivalirudin use during ePCI |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Clinical follow up at 3 days after ePCI
Secondary outcomes (1)
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
Measured: Clinical follow up at 7 days after ePCI
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2019
- Study start20 Sep 2019
- Primary completion1 Aug 2022
- Study completion1 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Coronary Heart DiseaseStudies of the same condition, open and under way.
- More trials run by Nanjing First Hospital, Nanjing Medical UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 330 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Zhiming Wu, MD, Principal investigator, Nanjing First Hospital, Nanjing Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04120961
- Sponsor's protocol ID
- KY20190823-05
- Status last verified
- Aug 2022
- First submitted
- 29 Sep 2019
- Last updated
- 9 Aug 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 25775052Lincoff 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.
PubMed 12588269Schulz 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.
PubMed 20150324Devereaux 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.
PubMed 21502650Wu Z, Meng P, Guo Y, You W, Wu X, Ye F. Prolonged infusion of bivalirudin after elective percutaneous coronary intervention protects against procedural myocardial injury (a COBER study)-a randomized trial. Sci Rep. 2023 Apr 24;13(1):6667. doi: 10.1038/s41598-023-34008-y.
PubMed 37095298
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Prolonged Use of Bivalirudin 4 Hours After Elective PCI in Patients With CHD (COBER Study)
- ClinicalTrials.gov ID
- NCT04120961
- Acronym / sponsor ID
- KY20190823-05
- Conditions
- Coronary Heart Disease
- Keywords
- bivalirudin, prolonged use, peri-operative myocardial injury, percutaneous coronary intervention
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 330 participants (actual)
- Lead sponsor
- Nanjing First Hospital, Nanjing Medical UniversityUniversity, hospital or other
- Study start
- 20 Sep 2019 (actual)
- Primary completion
- 1 Aug 2022 (actual)
- Study completion
- 1 Aug 2022 (actual)
- First posted
- 9 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| prolonged continuous use of bivalirudine | Experimental | Drug: prolonged continuous use of bivalirudinA total of 165 patients are assigned to group with prolonged continuous use of bivalirudin after randomization schedule. |
| bivalirudin use during ePCI | Other | Drug: bivalirudin use during ePCIA total of 165 patients are assigned to group with bivalirudin use during ePCI after randomization schedule. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- De novo lesions
- elective PCI
- Only single coronary artery treated at this time
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| prolonged continuous use of bivalirudinAlso: prolonged continuous use of bivalirudin 4 hours after elective PCIprolonged continuous use of bivalirudin 4 hours after elective PCI (dose: 0.75 mg/kg bolus plus 1.75 mg/kg per hour) | Drug | prolonged continuous use of bivalirudine |
| bivalirudin use during ePCIAlso: bivalirudin use during ePCI periodbivalirudin use during ePCI (0.75 mg/kg bolus plus 1.75 mg/kg per hour) | Drug | bivalirudin use during ePCI |
Primary outcome
The incidence rate of PMI in CHD patients 3 days after ePCI
Time frame: Clinical follow up at 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
1 secondary outcome
The incidence rate of MACEs and bleeding
Time frame: Clinical follow up at 7 days after ePCI
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2022.
- Background: PubMed 25775052Han 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.
- Background: PubMed 12588269Lincoff 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.
- Background: PubMed 20150324Schulz 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.
- Background: PubMed 21502650Devereaux 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.
- Derived from this study: PubMed 37095298Wu Z, Meng P, Guo Y, You W, Wu X, Ye F. Prolonged infusion of bivalirudin after elective percutaneous coronary intervention protects against procedural myocardial injury (a COBER study)-a randomized trial. Sci Rep. 2023 Apr 24;13(1):6667. doi: 10.1038/s41598-023-34008-y.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Zhiming Wu, MD principal investigator
Nanjing First Hospital, Nanjing Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing prolonged continuous use of bivalirudin and bivalirudin use during ePCI in people with Coronary Heart Disease, run by Nanjing First Hospital, Nanjing Medical University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The incidence rate of PMI in CHD patients 3 days after ePCI (time frame: Clinical follow up at 3 days after ePCI). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04120961, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Aug 2022.