Ignite Creation Date:
2024-05-05 @ 5:22 PM
Last Modification Date:
2024-10-26 @ 9:31 AM
Study NCT ID:
NCT00448461
Status:
COMPLETED
Last Update Posted:
2009-02-10
First Post:
2007-03-14
Brief Title:
Antithrombotic Regimens and Outcome
Sponsor:
Careggi Hospital
Organization:
Careggi Hospital
Study Overview
Official Title:
Comparison of Bivalirudin and Unfractioned Heparin in Elective Percutaneous Coronary Interventions
Status:
COMPLETED
Status Verified Date:
2009-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ARNO
Brief Summary:
PROTOCOL SYNOPSIS Title Comparison of bivalirudin and unfractioned heparin UFH protamine in elective percutaneous coronary interventions PCI
Design Prospective randomized controlled trial
Hypothesis Bivalirudin is superior to UFH protamine for the improvement of outcomes in patients undergoing elective PCI
Key Inclusion Criteria
Patients older than 18 years of age to undergo PCI Clopidogrel loading 6 hrs prior to PCI according to the PCI guidelines Informed written consent
Key Exclusion Criteria
ST-elevation myocardial infarction within the prior 48 hours Active bleeding bleeding diathesis recent surgery Severe renal failure Chronic coronary artery occlusion to be treated
Primary endpoint
Inhospital major bleeding
Secondary endpoints
1 Composite rate of death myocardial infarction MI or target vessel revascularization TVR inhospital and at 6 months
2 Composite rate of inhospital death MI or TVR and major bleeding
3 Major and minor bleedings
4 Total vascular complications
5 Post-procedure renal failure
Randomization
Bivalirudin versus unfractioned heparin followed by protamine at the end of the PCI procedure
Sample size
Assumed incidence of inhospital major bleeding of 6 in UFH protamine and of 2 in bivalirudin group for a power of 80 and a level of 005 for each group 425 patients are needed An interim analysis will be performed after the enrolment of 425 50 patients
Follow-up
Inhospital and 6-month clinical follow-up out-patient clinic or by phone
Design Prospective randomized controlled trial
Hypothesis Bivalirudin is superior to UFH protamine for the improvement of outcomes in patients undergoing elective PCI
Key Inclusion Criteria
Patients older than 18 years of age to undergo PCI Clopidogrel loading 6 hrs prior to PCI according to the PCI guidelines Informed written consent
Key Exclusion Criteria
ST-elevation myocardial infarction within the prior 48 hours Active bleeding bleeding diathesis recent surgery Severe renal failure Chronic coronary artery occlusion to be treated
Primary endpoint
Inhospital major bleeding
Secondary endpoints
1 Composite rate of death myocardial infarction MI or target vessel revascularization TVR inhospital and at 6 months
2 Composite rate of inhospital death MI or TVR and major bleeding
3 Major and minor bleedings
4 Total vascular complications
5 Post-procedure renal failure
Randomization
Bivalirudin versus unfractioned heparin followed by protamine at the end of the PCI procedure
Sample size
Assumed incidence of inhospital major bleeding of 6 in UFH protamine and of 2 in bivalirudin group for a power of 80 and a level of 005 for each group 425 patients are needed An interim analysis will be performed after the enrolment of 425 50 patients
Follow-up
Inhospital and 6-month clinical follow-up out-patient clinic or by phone
Detailed Description:
Bivalirudin a direct thrombin inhibitor has been recently introduced as an alternative to UFH given several important biologic and pharmacokinetic advantages12 In contrast to UFH it acts independently of antithrombin and inhibits both free and clotbound thrombin it is not neutralized by circulating inhibitors does not bind to plasma protein and cause thrombocytopenia12 In the Bivalirudin Angioplasty Study bivalirudin was associated with a 45 reduction in the relative risk for the composite of death myocardial infarction revascularization or hemorrhage as compared to UFH among patients with unstable angina undergoing percutaneous coronary angioplasty3 Recently in another randomized trial of patients with intermediate risk undergoing coronary stenting after varying pre-treatment intervals with different doses of thienopyridines use of bivalirudin was estimated to result in 38 reduction in the relative risk of death myocardial infarction urgent repeat revascularization or in-hospital major bleeding at 30 days compared to UFH4 In addition bivalirudin was associated with a similar rate of ischemic events and less major bleeding and estimated to be more cost-effective than abciximab administered in adjunct to UFH45 However previous studies have included patients treated with plain balloon angioplasty or stenting after inadequate pretreatment with thienopyridines ticlopidine or clopidogrel Recent guidelines recommend that all patients undergoing PCI must receive a loading dose of 300 - 600 mg of clopidogrel6 Clopidogrel is a thienopyridine that acts by irreversibly inhibiting the platelet adenosine 5- diphosphate ADP receptor Compared to ticlopidine it has the advantage of a more favourable side effect profile 7 8 and more rapid onset of action9 Pre-treatment with clopidogrel has been associated with better outcomes among patients undergoing PCI10-12 After a loading dose of 600 mg maximum inhibition of aggregation with clopidogrel is achieved within two hours13 The Intracoronary Stenting and Antithrombotic Regimen-Rapid Early Action for Coronary Treatment ISAR-REACT trial showed that after pre-treatment with 600 mg clopidogrel for at least 2 hours before intervention additional use of abicximab to UFH was not associated with any clinically measurable benefit among low-to-intermediate risk patients who underwent PCI14 On the other hand patients who received abciximab had a higher rate of thrombocytopenia and more frequently required blood transfusions Thus an antithrombotic strategy consisting of a loading dose of 600 mg clopidogrel in addition to UFH and aspirin is a safe and effective way to improve patients outcomes and reduce costs after PCI There are few data about the use of protamine neutralization of circulating heparin after successful stent implantation15-18 However all the previous studies showed no excess in ischemic complications after stent implantation and subsequent protamine administration with a strong potential for bleeding complication limitation
Based on the above-mentioned data it can be said that antithrombotic regimens based on either bivalirudin or UFH intraprocedurally followed by protamine neutralization are effective strategies to reduce ischemic and hemorrhagic complications in patients with coronary artery disease undergoing PCI At present it is not known whether bivalirudin is superior to UFH in patients who have been optimally pre-treated with a loading dose of clopidogrel
We designed this study to assess whether bivalirudin is superior to unfractioned heparin protamine in patients undergoing PCI All patients older than 18 years of age who require coronary angiography for suspected or established coronary artery disease but without ST-segment changes will receive a loading dose of 600 mg clopidogrel at least 2 hours prior to the procedure Eligible patients who do not meet the exclusion criteria and in whom angiography reveals that revascularization is required and the target lesions is are amenable to PCI will be randomized to receive a bolus of 140 Ukg of heparin or bivalirudin to be administered as an intravenous bolus of 075 mgkg prior to the start of the intervention followed by infusion of 175 mgkg per hour for the duration of the procedure All patients will receive aspirin indefinitely and clopidogrel for at least 1 month after PTCA or implantation of bare metal stents and for at least 6 months after implantation of drug-eluting stents clopidogrel treatment for more than 6 months will be encouraged19 The primary end point of the study is in-hospital major bleeding The study is designed to show whether bivalirudin is superior to UFH protamine with respect to the primary end point
Based on the above-mentioned data it can be said that antithrombotic regimens based on either bivalirudin or UFH intraprocedurally followed by protamine neutralization are effective strategies to reduce ischemic and hemorrhagic complications in patients with coronary artery disease undergoing PCI At present it is not known whether bivalirudin is superior to UFH in patients who have been optimally pre-treated with a loading dose of clopidogrel
We designed this study to assess whether bivalirudin is superior to unfractioned heparin protamine in patients undergoing PCI All patients older than 18 years of age who require coronary angiography for suspected or established coronary artery disease but without ST-segment changes will receive a loading dose of 600 mg clopidogrel at least 2 hours prior to the procedure Eligible patients who do not meet the exclusion criteria and in whom angiography reveals that revascularization is required and the target lesions is are amenable to PCI will be randomized to receive a bolus of 140 Ukg of heparin or bivalirudin to be administered as an intravenous bolus of 075 mgkg prior to the start of the intervention followed by infusion of 175 mgkg per hour for the duration of the procedure All patients will receive aspirin indefinitely and clopidogrel for at least 1 month after PTCA or implantation of bare metal stents and for at least 6 months after implantation of drug-eluting stents clopidogrel treatment for more than 6 months will be encouraged19 The primary end point of the study is in-hospital major bleeding The study is designed to show whether bivalirudin is superior to UFH protamine with respect to the primary end point
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None