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European Ambulance Acute Coronary Syndrome (ACS) Angiography Trial (EUROMAX)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01087723
Recruitment Status : Completed
First Posted : March 16, 2010
Results First Posted : February 12, 2016
Last Update Posted : February 12, 2016
Sponsor:
Information provided by (Responsible Party):
The Medicines Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Acute Coronary Syndrome
Interventions Drug: Bivalirudin
Drug: Heparin
Enrollment 2198
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Bivalirudin Standard of Care: Heparins With Optional GPI
Hide Arm/Group Description Given immediately upon enrolment as an intravenous (IV) bolus of 0.75 milligrams/kilogram (mg/kg), followed immediately by an infusion of 1.75 mg/kg/hour (mg/kg/h). This infusion was to be run continuously until completion of percutaneous coronary intervention (PCI), at which time the infusion was reduced to 0.25 mg/kg/h for at least 4 hours. An optional PCI-dose infusion of 1.75 mg/kg/h was also permitted for up to 4 hours at the discretion of the operator.

Standard-of-care anti-thrombotic therapy as outlined in the European Society of Cardiology Dosing Guidelines for Management of ST segment elevation acute coronary syndrome (STE-ACS ), not including bivalirudin: unfractionated heparin (UFH) (100 international units/kg [IU/kg] without glycoprotein IIb/IIIa inhibitor [GPI] and 60 IU/kg with GPI). Any of the following approved GPIs were used either as a routine strategy or as a bail out: eptifibatide (two 180-micrograms/kilogram [μg/kg] IV boluses with a 10-minute [min] interval followed by an infusion of 2.0 μg/kg/min for 72-96 hours); tirofiban (25 μg/kg followed by an infusion of 0.15 μg/kg/min for 18-24 hours); or abciximab (bolus of 0.25 mg/kg followed by an infusion of 0.125 μg/kg/min for 12-24 hours [maximum dose of 10 μg/min]).

For this study, the control consisted of treatment with UFH or low molecular weight heparin (LMWH) with or without GPI and is referred to as "heparins with optional GPI.”

Period Title: Overall Study
Started 1089 [1] 1109 [1]
Received at Least 1 Dose of Study Drug 1099 [2] 1094 [2]
Completed 1075 [3] 1089 [3]
Not Completed 14 20
Reason Not Completed
1 Year Visit Too Early (<335 days)             0             1
Withdrawal by Subject             10             13
Physician Decision             2             0
Lost to Follow-up             1             4
Reason Not Specified             1             2
[1]
Randomized participants who signed an informed consent form (ICF); Intent-to-treat (ITT) population
[2]
Participants who were randomized with signed ICF by treatment actually received; Safety population
[3]
Completed 1-year follow-up in the study
Arm/Group Title Bivalirudin Standard of Care: Heparins With Optional GPI Total
Hide Arm/Group Description Given immediately upon enrollment as an IV bolus of 0.75 mg/kg, followed immediately by an infusion of 1.75 mg/kg/h. This infusion was to be run continuously until completion of PCI, at which time the infusion was reduced to 0.25 mg/kg/h for at least 4 hours. An optional PCI-dose infusion of 1.75 mg/kg/h was also permitted for up to 4 hours at the discretion of the operator.

Standard-of-care anti-thrombotic therapy as outlined in the European Society of Cardiology Dosing Guidelines for Management of STE-ACS, not including bivalirudin: UFH (100 international IU/kg without GPI and 60 IU/kg with GPI). Any of the following approved GPIs were used either as a routine strategy or as a bail out: eptifibatide (two 180-μg/kg IV boluses with a 10-min interval followed by an infusion of 2.0 μg/kg/min for 72-96 hours); tirofiban (25 μg/kg followed by an infusion of 0.15 μg/kg/min for 18-24 hours); or abciximab (bolus of 0.25 mg/kg followed by an infusion of 0.125 μg/kg/min for 12-24 hours [maximum dose of 10 μg/min]).

For this study, the control consisted of treatment with UFH or LMWH with or without GPI and is referred to as "heparins with optional GPI.”

Total of all reporting groups
Overall Number of Baseline Participants 1089 1109 2198
Hide Baseline Analysis Population Description
Participants who were randomized and signed an ICF; ITT population
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1089 participants 1109 participants 2198 participants
61.4  (12.8) 62.0  (13.1) 61.7  (13.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1089 participants 1109 participants 2198 participants
Female
275
  25.3%
248
  22.4%
523
  23.8%
Male
814
  74.7%
861
  77.6%
1675
  76.2%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1089 participants 1109 participants 2198 participants
Austria 4 5 9
Czech Republic 0 1 1
Netherlands 377 391 768
Denmark 78 72 150
Poland 55 56 111
Italy 31 41 72
France 398 397 795
Germany 139 140 279
Slovenia 7 6 13
Medical history: Participant Has Diabetes  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1089 participants 1109 participants 2198 participants
127 169 296
Medical history: Participant Is a Current smoker (within past 30 days)  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1089 participants 1109 participants 2198 participants
453 472 925
Medical history: Participant Has Hypertension  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1089 participants 1109 participants 2198 participants
459 504 963
Medical history: Participant Has Hyperlipidemia   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1089 participants 1109 participants 2198 participants
398 417 815
[1]
Measure Description: Participant has known hyperlipidemia or is on lipid-lowering drugs
Medical history: Participant Has Had Previous myocardial infarction (MI)  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1089 participants 1109 participants 2198 participants
380 113 493
1.Primary Outcome
Title The Composite Incidence of Death and Non-coronary Artery Bypass Graft (CABG) Major Bleeding
Hide Description A participant was defined to have had a composite event if the participant experienced at least 1 of the 2 components (death or non-CABG major bleeding) of the composite. Incidence=the number of participants to experience the event/total number of at risk participants x 100. Death was defined as death from any cause at any time. Non-CABG major bleeding was defined as any 1 of the following: intra-cranial, retroperitoneal, intraocular, access site hemorrhage requiring radiological or surgical intervention, reduction in hemoglobin (Hb) concentration of >4 grams/deciliter (g/dL) without an overt source of bleeding, reduction in hemoglobin concentration of >3 g/dL with an overt source of bleeding; re-intervention for bleeding, or use of any blood product transfusion.
Time Frame Within 30 days
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who were randomized and signed an ICF; ITT population
Arm/Group Title Bivalirudin Standard of Care: Heparins With Optional GPI
Hide Arm/Group Description:
Given immediately upon enrollment as an IV bolus of 0.75 mg/kg, followed immediately by an infusion of 1.75 mg/kg/h. This infusion was to be run continuously until completion of PCI, at which time the infusion was reduced to 0.25 mg/kg/h for at least 4 hours. An optional PCI-dose infusion of 1.75 mg/kg/h was also permitted for up to 4 hours at the discretion of the operator.

Standard-of-care anti-thrombotic therapy as outlined in the European Society of Cardiology Dosing Guidelines for Management of STE-ACS, not including bivalirudin: UFH (100 international IU/kg without GPI and 60 IU/kg with GPI). Any of the following approved GPIs were used either as a routine strategy or as a bail out: eptifibatide (two 180-μg/kg IV boluses with a 10-min interval followed by an infusion of 2.0 μg/kg/min for 72-96 hours); tirofiban (25 μg/kg followed by an infusion of 0.15 μg/kg/min for 18-24 hours); or abciximab (bolus of 0.25 mg/kg followed by an infusion of 0.125 μg/kg/min for 12-24 hours [maximum dose of 10 μg/min]).

For this study, the control consisted of treatment with UFH or LMWH with or without GPI and is referred to as "heparins with optional GPI.”

Overall Number of Participants Analyzed 1089 1109
Measure Type: Number
Unit of Measure: percentage of participants
5.1 8.5
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bivalirudin, Standard of Care: Heparins With Optional GPI
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0014
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Relative risk
Estimated Value 0.60
Confidence Interval (2-Sided) 95%
0.43 to 0.82
Estimation Comments [Not Specified]
2.Secondary Outcome
Title The Composite Incidence of Death, Re-infarction (MI), or Non-CABG Major Bleeding
Hide Description A participant had a composite event if the participant experienced at least 1 of the 3 components (death, re-infarction [MI], or non-CABG major bleeding) of the composite. Incidence=the number of participants to experience the event/total number of at risk participants x 100. Death was defined as death from any cause at any time. Non-CABG major bleeding was defined as any one of the following: intracranial, retroperitoneal, intraocular, access site hemorrhage requiring radiological or surgical intervention, reduction in Hb concentration of >4 g/dL without an overt source of bleeding, reduction in hemoglobin concentration of >3 g/dL with an overt source of bleeding, re-intervention for bleeding, use of any blood product transfusion. MI was defined as a positive diagnosis of re-infarction (new event) not associated with index PCI.
Time Frame Within 30 days
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who were randomized and signed an ICF; ITT population
Arm/Group Title Bivalirudin Standard of Care: Heparins With Optional GPI
Hide Arm/Group Description:
Given immediately upon enrollment as an IV bolus of 0.75 mg/kg, followed immediately by an infusion of 1.75 mg/kg/h. This infusion was to be run continuously until completion of PCI, at which time the infusion was reduced to 0.25 mg/kg/h for at least 4 hours. An optional PCI-dose infusion of 1.75 mg/kg/h was also permitted for up to 4 hours at the discretion of the operator.

Standard-of-care anti-thrombotic therapy as outlined in the European Society of Cardiology Dosing Guidelines for Management of STE-ACS, not including bivalirudin: UFH (100 international IU/kg without GPI and 60 IU/kg with GPI). Any of the following approved GPIs were used either as a routine strategy or as a bail out: eptifibatide (two 180-μg/kg IV boluses with a 10-min interval followed by an infusion of 2.0 μg/kg/min for 72-96 hours); tirofiban (25 μg/kg followed by an infusion of 0.15 μg/kg/min for 18-24 hours); or abciximab (bolus of 0.25 mg/kg followed by an infusion of 0.125 μg/kg/min for 12-24 hours [maximum dose of 10 μg/min]).

For this study, the control consisted of treatment with UFH or LMWH with or without GPI and is referred to as "heparins with optional GPI.”

Overall Number of Participants Analyzed 1089 1109
Measure Type: Number
Unit of Measure: percentage of participants
6.6 9.2
3.Secondary Outcome
Title The Incidence of Death, Re-infarction, Non-CABG-related Major Bleeding, or Ischemia-driven Revascularization (IDR)
Hide Description Incidence=number of participants to experience the event/total number of at risk participants x 100. Death from any cause at any time. Re-infarction was a positive diagnosis of re-infarction not associated with index PCI. Non-CABG major bleeding was any 1 of: intracranial, retroperitoneal, intraocular, access site hemorrhage requiring radiological or surgical intervention, reduction in Hb concentration of >4 g/dL without an overt source of bleeding, reduction in hemoglobin concentration of >3 g/dL with an overt source of bleeding, re-intervention for bleeding, use of any blood product transfusion. IDR was any refractory ischemia-driven repeat percutaneous intervention or bypass graft surgery involving any native coronary or pre-existing bypass graft vessel. In the absence of pain, new ST segment changes indicative of ischemia, acute pulmonary edema, ventricular arrhythmias, or hemodynamic instability presumed to be ischemic in origin, will constitute sufficient evidence of ischemia.
Time Frame Within 30 days
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who were randomized and signed an ICF; ITT population
Arm/Group Title Bivalirudin Standard of Care: Heparins With Optional GPI
Hide Arm/Group Description:
Given immediately upon enrollment as an IV bolus of 0.75 mg/kg, followed immediately by an infusion of 1.75 mg/kg/h. This infusion was to be run continuously until completion of PCI, at which time the infusion was reduced to 0.25 mg/kg/h for at least 4 hours. An optional PCI-dose infusion of 1.75 mg/kg/h was also permitted for up to 4 hours at the discretion of the operator.

Standard-of-care anti-thrombotic therapy as outlined in the European Society of Cardiology Dosing Guidelines for Management of STE-ACS, not including bivalirudin: UFH (100 international IU/kg without GPI and 60 IU/kg with GPI). Any of the following approved GPIs were used either as a routine strategy or as a bail out: eptifibatide (two 180-μg/kg IV boluses with a 10-min interval followed by an infusion of 2.0 μg/kg/min for 72-96 hours); tirofiban (25 μg/kg followed by an infusion of 0.15 μg/kg/min for 18-24 hours); or abciximab (bolus of 0.25 mg/kg followed by an infusion of 0.125 μg/kg/min for 12-24 hours [maximum dose of 10 μg/min]).

For this study, the control consisted of treatment with UFH or LMWH with or without GPI and is referred to as "heparins with optional GPI.”

Overall Number of Participants Analyzed 1089 1109
Measure Type: Number
Unit of Measure: percentage of participants
Death 2.9 3.1
Re-infarction 1.7 0.9
Non-CABG-related major bleeding 2.6 6.0
IDR 2.2 1.5
4.Secondary Outcome
Title The Incidence of Death at 1 Year
Hide Description Incidence=the number of participants to experience the event/total number of at risk participants x 100. Death was defined as death from any cause at any time.
Time Frame Within 1 Year
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who were randomized and signed an ICF; ITT population
Arm/Group Title Bivalirudin Standard of Care: Heparins With Optional GPI
Hide Arm/Group Description:
Given immediately upon enrollment as an IV bolus of 0.75 mg/kg, followed immediately by an infusion of 1.75 mg/kg/h. This infusion was to be run continuously until completion of PCI, at which time the infusion was reduced to 0.25 mg/kg/h for at least 4 hours. An optional PCI-dose infusion of 1.75 mg/kg/h was also permitted for up to 4 hours at the discretion of the operator.

Standard-of-care anti-thrombotic therapy as outlined in the European Society of Cardiology Dosing Guidelines for Management of STE-ACS, not including bivalirudin: UFH (100 international IU/kg without GPI and 60 IU/kg with GPI). Any of the following approved GPIs were used either as a routine strategy or as a bail out: eptifibatide (two 180-μg/kg IV boluses with a 10-min interval followed by an infusion of 2.0 μg/kg/min for 72-96 hours); tirofiban (25 μg/kg followed by an infusion of 0.15 μg/kg/min for 18-24 hours); or abciximab (bolus of 0.25 mg/kg followed by an infusion of 0.125 μg/kg/min for 12-24 hours [maximum dose of 10 μg/min]).

For this study, the control consisted of treatment with UFH or LMWH with or without GPI and is referred to as "heparins with optional GPI.”

Overall Number of Participants Analyzed 1089 1109
Measure Type: Number
Unit of Measure: percentage of participants
5.4 5.3
5.Secondary Outcome
Title The Incidence of Major Bleeding: Thrombolysis in MI (TIMI) and Global Utilization of Streptokinase and tPA for Occluded Coronary Arteries (GUSTO)
Hide Description Incidence=the number of participants to experience the event/total number of at risk participants x 100. Major bleeding based on TIMI criteria was defined as any intra-cranial bleeding, or any bleeding associated with clinically overt signs associated with a drop in Hb of >5 g/dL (or, when Hb was not available, an absolute drop in hematocrit [Hct] >15%). Major bleeding based on GUSTO criteria was defined as severe/life-threatening: intra-cranial hemorrhage or resulting in substantial hemodynamic compromise requiring treatment.
Time Frame Within 30 days
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who were randomized and signed an ICF; ITT population
Arm/Group Title Bivalirudin Standard of Care: Heparins With Optional GPI
Hide Arm/Group Description:
Given immediately upon enrollment as an IV bolus of 0.75 mg/kg, followed immediately by an infusion of 1.75 mg/kg/h. This infusion was to be run continuously until completion of PCI, at which time the infusion was reduced to 0.25 mg/kg/h for at least 4 hours. An optional PCI-dose infusion of 1.75 mg/kg/h was also permitted for up to 4 hours at the discretion of the operator.

Standard-of-care anti-thrombotic therapy as outlined in the European Society of Cardiology Dosing Guidelines for Management of STE-ACS, not including bivalirudin: UFH (100 international IU/kg without GPI and 60 IU/kg with GPI). Any of the following approved GPIs were used either as a routine strategy or as a bail out: eptifibatide (two 180-μg/kg IV boluses with a 10-min interval followed by an infusion of 2.0 μg/kg/min for 72-96 hours); tirofiban (25 μg/kg followed by an infusion of 0.15 μg/kg/min for 18-24 hours); or abciximab (bolus of 0.25 mg/kg followed by an infusion of 0.125 μg/kg/min for 12-24 hours [maximum dose of 10 μg/min]).

For this study, the control consisted of treatment with UFH or LMWH with or without GPI and is referred to as "heparins with optional GPI.”

Overall Number of Participants Analyzed 1089 1109
Measure Type: Number
Unit of Measure: percentage of participants
Major bleeding: TIMI 1.3 2.1
Major bleeding: GUSTO 1.3 2.3
6.Secondary Outcome
Title The Incidence of Minor Bleeding: TIMI and GUSTO
Hide Description Incidence=the number of participants to experience the event/total number of at risk participants x 100. Minor bleeding based on TIMI criteria was defined as any clinically overt sign of bleeding (including observation by imaging techniques) that was associated with a fall in Hb of ≥3 g/dL and ≤5 g/dL (or, when Hb was not available, an absolute drop in Hct of ≥9% and ≤15%). Minor bleeding based on GUSTO criteria was defined as other bleed not requiring blood transfusion or causing hemodynamic compromise.
Time Frame Within 30 days
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who were randomized and signed an ICF; ITT population
Arm/Group Title Bivalirudin Standard of Care: Heparins With Optional GPI
Hide Arm/Group Description:
Given immediately upon enrollment as an IV bolus of 0.75 mg/kg, followed immediately by an infusion of 1.75 mg/kg/h. This infusion was to be run continuously until completion of PCI, at which time the infusion was reduced to 0.25 mg/kg/h for at least 4 hours. An optional PCI-dose infusion of 1.75 mg/kg/h was also permitted for up to 4 hours at the discretion of the operator.

Standard-of-care anti-thrombotic therapy as outlined in the European Society of Cardiology Dosing Guidelines for Management of STE-ACS, not including bivalirudin: UFH (100 international IU/kg without GPI and 60 IU/kg with GPI). Any of the following approved GPIs were used either as a routine strategy or as a bail out: eptifibatide (two 180-μg/kg IV boluses with a 10-min interval followed by an infusion of 2.0 μg/kg/min for 72-96 hours); tirofiban (25 μg/kg followed by an infusion of 0.15 μg/kg/min for 18-24 hours); or abciximab (bolus of 0.25 mg/kg followed by an infusion of 0.125 μg/kg/min for 12-24 hours [maximum dose of 10 μg/min]).

For this study, the control consisted of treatment with UFH or LMWH with or without GPI and is referred to as "heparins with optional GPI.”

Overall Number of Participants Analyzed 1089 1109
Measure Type: Number
Unit of Measure: percentage of participants
Minor bleeding: TIMI 6.5 11.2
Minor bleeding: GUSTO 6.5 11.0
7.Secondary Outcome
Title The Incidence of Stent Thrombosis (Academic Research Consortium [ARC Definition])
Hide Description Incidence=the number of participants to experience the event/total number of at risk participants x 100. Stent thrombosis, based on the ARC definition, was defined as angiographic confirmation of stent thrombosis, non-occlusive thrombus, occlusive thrombus, or pathological confirmation of stent thrombosis.
Time Frame Within 30 days
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who were randomized and signed an ICF; ITT population
Arm/Group Title Bivalirudin Standard of Care: Heparins With Optional GPI
Hide Arm/Group Description:
Given immediately upon enrollment as an IV bolus of 0.75 mg/kg, followed immediately by an infusion of 1.75 mg/kg/h. This infusion was to be run continuously until completion of PCI, at which time the infusion was reduced to 0.25 mg/kg/h for at least 4 hours. An optional PCI-dose infusion of 1.75 mg/kg/h was also permitted for up to 4 hours at the discretion of the operator.

Standard-of-care anti-thrombotic therapy as outlined in the European Society of Cardiology Dosing Guidelines for Management of STE-ACS, not including bivalirudin: UFH (100 international IU/kg without GPI and 60 IU/kg with GPI). Any of the following approved GPIs were used either as a routine strategy or as a bail out: eptifibatide (two 180-μg/kg IV boluses with a 10-min interval followed by an infusion of 2.0 μg/kg/min for 72-96 hours); tirofiban (25 μg/kg followed by an infusion of 0.15 μg/kg/min for 18-24 hours); or abciximab (bolus of 0.25 mg/kg followed by an infusion of 0.125 μg/kg/min for 12-24 hours [maximum dose of 10 μg/min]).

For this study, the control consisted of treatment with UFH or LMWH with or without GPI and is referred to as "heparins with optional GPI.”

Overall Number of Participants Analyzed 1089 1109
Measure Type: Number
Unit of Measure: percentage of participants
1.6 0.5
8.Secondary Outcome
Title The Incidence of Thrombocytopenia
Hide Description Incidence=the number of participants to experience the event/total number of at risk participants x 100. Thrombocytopenia was defined as a post-procedural platelet count <100,000 cells/millimeter cubed (cells/mm^3) in a participant with a baseline or pre-procedural platelet count >100,000 cells/mm^3.
Time Frame Within 30 days
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who were randomized and signed an ICF; ITT population
Arm/Group Title Bivalirudin Standard of Care: Heparins With Optional GPI
Hide Arm/Group Description:
Given immediately upon enrollment as an IV bolus of 0.75 mg/kg, followed immediately by an infusion of 1.75 mg/kg/h. This infusion was to be run continuously until completion of PCI, at which time the infusion was reduced to 0.25 mg/kg/h for at least 4 hours. An optional PCI-dose infusion of 1.75 mg/kg/h was also permitted for up to 4 hours at the discretion of the operator.

Standard-of-care anti-thrombotic therapy as outlined in the European Society of Cardiology Dosing Guidelines for Management of STE-ACS, not including bivalirudin: UFH (100 international IU/kg without GPI and 60 IU/kg with GPI). Any of the following approved GPIs were used either as a routine strategy or as a bail out: eptifibatide (two 180-μg/kg IV boluses with a 10-min interval followed by an infusion of 2.0 μg/kg/min for 72-96 hours); tirofiban (25 μg/kg followed by an infusion of 0.15 μg/kg/min for 18-24 hours); or abciximab (bolus of 0.25 mg/kg followed by an infusion of 0.125 μg/kg/min for 12-24 hours [maximum dose of 10 μg/min]).

For this study, the control consisted of treatment with UFH or LMWH with or without GPI and is referred to as "heparins with optional GPI.”

Overall Number of Participants Analyzed 1089 1109
Measure Type: Number
Unit of Measure: percentage of participants
0.7 1.4
9.Secondary Outcome
Title The Incidence of Stroke
Hide Description Incidence=the number of participants to experience the event/total number of at risk participants x 100. Stroke was defined as a sudden, focal neurological defect resulting from a cerebrovascular cause, resulting in death or lasting greater than 24 hours that was not due to a readily identifiable cause, such as a tumor, infection, or trauma.
Time Frame Within 30 days
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who were randomized and signed an ICF; ITT population
Arm/Group Title Bivalirudin Standard of Care: Heparins With Optional GPI
Hide Arm/Group Description:
Given immediately upon enrollment as an IV bolus of 0.75 mg/kg, followed immediately by an infusion of 1.75 mg/kg/h. This infusion was to be run continuously until completion of PCI, at which time the infusion was reduced to 0.25 mg/kg/h for at least 4 hours. An optional PCI-dose infusion of 1.75 mg/kg/h was also permitted for up to 4 hours at the discretion of the operator.

Standard-of-care anti-thrombotic therapy as outlined in the European Society of Cardiology Dosing Guidelines for Management of STE-ACS, not including bivalirudin: UFH (100 international IU/kg without GPI and 60 IU/kg with GPI). Any of the following approved GPIs were used either as a routine strategy or as a bail out: eptifibatide (two 180-μg/kg IV boluses with a 10-min interval followed by an infusion of 2.0 μg/kg/min for 72-96 hours); tirofiban (25 μg/kg followed by an infusion of 0.15 μg/kg/min for 18-24 hours); or abciximab (bolus of 0.25 mg/kg followed by an infusion of 0.125 μg/kg/min for 12-24 hours [maximum dose of 10 μg/min]).

For this study, the control consisted of treatment with UFH or LMWH with or without GPI and is referred to as "heparins with optional GPI.”

Overall Number of Participants Analyzed 1089 1109
Measure Type: Number
Unit of Measure: percentage of participants
0.6 1.0
Time Frame From screening to Day 30
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Bivalirudin Standard of Care: Heparins With Optional GPI
Hide Arm/Group Description Given immediately upon enrollment as an IV bolus of 0.75 mg/kg, followed immediately by an infusion of 1.75 mg/kg/h. This infusion was to be run continuously until completion of PCI, at which time the infusion was reduced to 0.25 mg/kg/h for at least 4 hours. An optional PCI-dose infusion of 1.75 mg/kg/h was also permitted for up to 4 hours at the discretion of the operator.

Standard-of-care anti-thrombotic therapy as outlined in the European Society of Cardiology Dosing Guidelines for Management of STE-ACS, not including bivalirudin: UFH (100 international IU/kg without GPI and 60 IU/kg with GPI). Any of the following approved GPIs were used either as a routine strategy or as a bail out: eptifibatide (two 180-μg/kg IV boluses with a 10-min interval followed by an infusion of 2.0 μg/kg/min for 72-96 hours); tirofiban (25 μg/kg followed by an infusion of 0.15 μg/kg/min for 18-24 hours); or abciximab (bolus of 0.25 mg/kg followed by an infusion of 0.125 μg/kg/min for 12-24 hours [maximum dose of 10 μg/min]).

For this study, the control consisted of treatment with UFH or LMWH with or without GPI and is referred to as "heparins with optional GPI.”

All-Cause Mortality
Bivalirudin Standard of Care: Heparins With Optional GPI
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Bivalirudin Standard of Care: Heparins With Optional GPI
Affected / at Risk (%) Affected / at Risk (%)
Total   145/1099 (13.19%)   129/1094 (11.79%) 
Cardiac disorders     
Ventricular fibrillation  1  39/1099 (3.55%)  28/1094 (2.56%) 
Cardiogenic shock  1  21/1099 (1.91%)  17/1094 (1.55%) 
Cardiac arrest  1  7/1099 (0.64%)  17/1094 (1.55%) 
Cardiac failure  1  8/1099 (0.73%)  10/1094 (0.91%) 
Coronary artery dissection  1  7/1099 (0.64%)  2/1094 (0.18%) 
Ventricular tachycardia  1  3/1099 (0.27%)  4/1094 (0.37%) 
Bradycardia  1  2/1099 (0.18%)  3/1094 (0.27%) 
Atrioventricular block complete  1  3/1099 (0.27%)  2/1094 (0.18%) 
Angina pectoris  1  2/1099 (0.18%)  3/1094 (0.27%) 
Intracardiac thrombus  1  3/1099 (0.27%)  1/1094 (0.09%) 
Atrial fibrillation  1  2/1099 (0.18%)  2/1094 (0.18%) 
Coronary artery perforation  1  2/1099 (0.18%)  1/1094 (0.09%) 
Ventricular septal defect acquired  1  2/1099 (0.18%)  0/1094 (0.00%) 
Tachycardia  1  0/1099 (0.00%)  2/1094 (0.18%) 
Coronary no-reflow phenomenon  1  1/1099 (0.09%)  1/1094 (0.09%) 
Coronary artery stenosis  1  0/1099 (0.00%)  2/1094 (0.18%) 
Cardio-respiratory arrest  1  2/1099 (0.18%)  0/1094 (0.00%) 
Atrioventricular block  1  2/1099 (0.18%)  0/1094 (0.00%) 
Acute myocardial infarction  1  0/1099 (0.00%)  2/1094 (0.18%) 
Ventricular extrasystoles  1  1/1099 (0.09%)  0/1094 (0.00%) 
Ventricular arrhythmia  1  0/1099 (0.00%)  1/1094 (0.09%) 
Ventricle rupture  1  1/1099 (0.09%)  0/1094 (0.00%) 
Stress cardiomyopathy  1  1/1099 (0.09%)  0/1094 (0.00%) 
Sinus arrest  1  1/1099 (0.09%)  0/1094 (0.00%) 
Sick sinus syndrome  1  1/1099 (0.09%)  0/1094 (0.00%) 
Pulseless electrical activity  1  0/1099 (0.00%)  1/1094 (0.09%) 
Pericarditis  1  1/1099 (0.09%)  0/1094 (0.00%) 
Pericardial effusion  1  1/1099 (0.09%)  0/1094 (0.00%) 
Papillary muscle rupture  1  0/1099 (0.00%)  1/1094 (0.09%) 
Palpitations  1  1/1099 (0.09%)  0/1094 (0.00%) 
Myocardial infarction  1  0/1099 (0.00%)  1/1094 (0.09%) 
Mitral valve incompetence  1  1/1099 (0.09%)  0/1094 (0.00%) 
Interventricular septum rupture  1  0/1099 (0.00%)  1/1094 (0.09%) 
Cardiac tamponade  1  1/1099 (0.09%)  0/1094 (0.00%) 
Cardiac failure acute  1  0/1099 (0.00%)  1/1094 (0.09%) 
Cardiac disorder  1  1/1099 (0.09%)  0/1094 (0.00%) 
Cardiac asthma  1  1/1099 (0.09%)  0/1094 (0.00%) 
Atrioventricular block second degree  1  1/1099 (0.09%)  0/1094 (0.00%) 
Angina unstable  1  0/1099 (0.00%)  1/1094 (0.09%) 
Congenital, familial and genetic disorders     
Ventricular septal defect  1  1/1099 (0.09%)  0/1094 (0.00%) 
Gastrointestinal disorders     
Intestinal infarction  1  1/1099 (0.09%)  1/1094 (0.09%) 
Ileus  1  0/1099 (0.00%)  1/1094 (0.09%) 
Abdominal wall haemorrhage  1  1/1099 (0.09%)  0/1094 (0.00%) 
Abdominal pain upper  1  0/1099 (0.00%)  1/1094 (0.09%) 
General disorders     
Chest pain  1  5/1099 (0.45%)  3/1094 (0.27%) 
Multi-organ failure  1  3/1099 (0.27%)  0/1094 (0.00%) 
Non-cardiac chest pain  1  1/1099 (0.09%)  1/1094 (0.09%) 
Death  1  1/1099 (0.09%)  1/1094 (0.09%) 
Sudden cardiac death  1  1/1099 (0.09%)  0/1094 (0.00%) 
Malaise  1  1/1099 (0.09%)  0/1094 (0.00%) 
Chest discomfort  1  1/1099 (0.09%)  0/1094 (0.00%) 
Cardiac death  1  0/1099 (0.00%)  1/1094 (0.09%) 
Hepatobiliary disorders     
Cholelithiasis  1  1/1099 (0.09%)  0/1094 (0.00%) 
Infections and infestations     
Pneumonia  1  2/1099 (0.18%)  5/1094 (0.46%) 
Septic shock  1  3/1099 (0.27%)  0/1094 (0.00%) 
Urinary tract infection  1  1/1099 (0.09%)  1/1094 (0.09%) 
Sepsis  1  0/1099 (0.00%)  1/1094 (0.09%) 
Pneumonia staphylococcal  1  1/1099 (0.09%)  0/1094 (0.00%) 
Pneumonia haemophilus  1  1/1099 (0.09%)  0/1094 (0.00%) 
Clostridial infection  1  0/1099 (0.00%)  1/1094 (0.09%) 
Bronchitis  1  0/1099 (0.00%)  1/1094 (0.09%) 
Appendicitis  1  0/1099 (0.00%)  1/1094 (0.09%) 
Injury, poisoning and procedural complications     
Gastrointestinal injury  1  1/1099 (0.09%)  0/1094 (0.00%) 
Facial bones fracture  1  0/1099 (0.00%)  1/1094 (0.09%) 
Investigations     
Arteriogram coronary  1  1/1099 (0.09%)  0/1094 (0.00%) 
Musculoskeletal and connective tissue disorders     
Compartment syndrome  1  1/1099 (0.09%)  0/1094 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Plasmacytoma  1  1/1099 (0.09%)  0/1094 (0.00%) 
Pancreatic neoplasm  1  1/1099 (0.09%)  0/1094 (0.00%) 
Abdominal neoplasm  1  0/1099 (0.00%)  1/1094 (0.09%) 
Nervous system disorders     
Syncope  1  2/1099 (0.18%)  0/1094 (0.00%) 
Presyncope  1  1/1099 (0.09%)  0/1094 (0.00%) 
Ischaemic stroke  1  1/1099 (0.09%)  0/1094 (0.00%) 
Hypotonia  1  1/1099 (0.09%)  0/1094 (0.00%) 
Dizziness  1  0/1099 (0.00%)  1/1094 (0.09%) 
Cerebral infarction  1  0/1099 (0.00%)  1/1094 (0.09%) 
Psychiatric disorders     
Hallucination  1  0/1099 (0.00%)  1/1094 (0.09%) 
Renal and urinary disorders     
Renal failure acute  1  4/1099 (0.36%)  4/1094 (0.37%) 
Renal failure  1  1/1099 (0.09%)  0/1094 (0.00%) 
Nephropathy toxic  1  0/1099 (0.00%)  1/1094 (0.09%) 
Calculus urinary  1  0/1099 (0.00%)  1/1094 (0.09%) 
Respiratory, thoracic and mediastinal disorders     
Acute pulmonary oedema  1  3/1099 (0.27%)  5/1094 (0.46%) 
Pulmonary oedema  1  2/1099 (0.18%)  1/1094 (0.09%) 
Dyspnoea  1  2/1099 (0.18%)  1/1094 (0.09%) 
Pleural effusion  1  1/1099 (0.09%)  1/1094 (0.09%) 
Lung disorder  1  0/1099 (0.00%)  2/1094 (0.18%) 
Chronic obstructive pulmonary disease  1  1/1099 (0.09%)  1/1094 (0.09%) 
Respiratory failure  1  0/1099 (0.00%)  1/1094 (0.09%) 
Orthopnoea  1  0/1099 (0.00%)  1/1094 (0.09%) 
Laryngeal oedema  1  1/1099 (0.09%)  0/1094 (0.00%) 
Dyspnoea exertional  1  0/1099 (0.00%)  1/1094 (0.09%) 
Vascular disorders     
Aortic dissection  1  4/1099 (0.36%)  0/1094 (0.00%) 
Hypotension  1  0/1099 (0.00%)  2/1094 (0.18%) 
Aortic stenosis  1  1/1099 (0.09%)  1/1094 (0.09%) 
Aortic aneurysm rupture  1  2/1099 (0.18%)  0/1094 (0.00%) 
Reperfusion injury  1  1/1099 (0.09%)  0/1094 (0.00%) 
Hypertensive crisis  1  0/1099 (0.00%)  1/1094 (0.09%) 
Haemodynamic instability  1  1/1099 (0.09%)  0/1094 (0.00%) 
Circulatory collapse  1  1/1099 (0.09%)  0/1094 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (12.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Bivalirudin Standard of Care: Heparins With Optional GPI
Affected / at Risk (%) Affected / at Risk (%)
Total   134/1099 (12.19%)   119/1094 (10.88%) 
Cardiac disorders     
Ventricular tachycardia  1  57/1099 (5.19%)  39/1094 (3.56%) 
Atrial fibrillation  1  35/1099 (3.18%)  35/1094 (3.20%) 
Bradycardia  1  20/1099 (1.82%)  25/1094 (2.29%) 
Vascular disorders     
Hypotension  1  22/1099 (2.00%)  20/1094 (1.83%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (12.1)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
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Name/Title: Global Health Science Center
Organization: The Medicines Company
Phone: 800-388-1183
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: The Medicines Company
ClinicalTrials.gov Identifier: NCT01087723     History of Changes
Other Study ID Numbers: TMC-BIV-08-03
First Submitted: March 12, 2010
First Posted: March 16, 2010
Results First Submitted: January 13, 2016
Results First Posted: February 12, 2016
Last Update Posted: February 12, 2016