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    Clinical Trial Results:
    Multi-centre, multi-national, prospective, randomised, open-label, comparison of bivalirudin to other guideline based current therapies (excluding bivalirudin)

    Summary
    EudraCT number
    		 2008-007290-20
    Trial protocol
    		 DE   AT   DK   FR   NL   CZ   ES   PL   IT   SI  
    Global end of trial date
    01 Aug 2014

    Results information
    Results version number
    		 v1(current)
    This version publication date
    22 May 2016
    First version publication date
    22 May 2016
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    TMC-BIV-08-03
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01087723
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    The Medicines Company
    Sponsor organisation address
    8 Sylvan Way, Parsippany, United States,
    Public contact
    Global Health Science Center, The Medicines Company, 41044 800-388-1183, medical.information@themedco.com.us
    Scientific contact
    Global Health Science Center, The Medicines Company, 41044 800-388-1183, medical.information@themedco.com.us
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    01 Aug 2014
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    01 Aug 2013
    Global end of trial reached?
    Yes
    Global end of trial date
    01 Aug 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To show that the early administration of bivalirudin improves 30-day outcomes when compared to the current standard of care in participants with ST segment elevation acute coronary syndrome (STE-ACS), intended for a primary percutaneous coronary intervention (PCI) management strategy, presenting either via ambulance or to centers where PCI is not performed.
    Protection of trial subjects
    This study was conducted in accordance with International Conference on Harmonisation (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the country or countries in which a study is conducted.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Mar 2010
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Czech Republic: 1
    Country: Number of subjects enrolled
    Netherlands: 768
    Country: Number of subjects enrolled
    Denmark: 150
    Country: Number of subjects enrolled
    Poland: 111
    Country: Number of subjects enrolled
    Italy: 72
    Country: Number of subjects enrolled
    France: 795
    Country: Number of subjects enrolled
    Germany: 279
    Country: Number of subjects enrolled
    Slovenia: 13
    Country: Number of subjects enrolled
    Austria: 9
    Worldwide total number of subjects
    2198
    EEA total number of subjects
    2198
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    1310
    From 65 to 84 years
    801
    85 years and over
    87

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 The decision to randomize participants was made by a qualified physician or paramedic who was present at the time. Participants were included in the study if they presented either via ambulance or to a center where PCI was not performed and met inclusion criteria.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Bivalirudin
    Arm 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.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Bivalirudin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Anticoagulant and preservative solution for blood
    Routes of administration
    Intravenous use
    Dosage and administration details
    Given immediately upon enrollment as an intravenous (IV) bolus of 0.75 mg/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 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.

    Arm title
    		 Standard of Care: Heparins with optional GPI
    Arm description
    		 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.”
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Standard of Care: Heparins with Optional GPI
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Anticoagulant and preservative solution for blood
    Routes of administration
    Intravenous use
    Dosage and administration details
    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 units/kg [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-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.”

    Number of subjects in period 1
    		Bivalirudin Standard of Care: Heparins with optional GPI
    Started
    1089
    1109
    Received at least 1 dose of study drug
    1089
    1094
    Additional by treatment received
    10 [1]
    0 [2]
    Completed
    1075
    1089
    Not completed
    14
    20
         Physician decision
    2
    -
         Consent withdrawn by subject
    10
    13
         1 Year Visit Too Early (<335 days)
    -
    1
         Reason Not Specified
    1
    2
         Lost to follow-up
    1
    4
    Notes
    [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: A total of 1089 participants were randomized and signed an informed consent form (ICF). This represents the Intent-to-treat (ITT) population. A total of 1099 participants were randomized with signed ICFs and who actually received this treatment (bivalirudin). This cohort represents the as-treated Safety population.
    [2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: No additional participants were randomized and signed an informed consent form (ICF). The as-treated Safety population is consistent with the number of participants that received at least 1 dose of study drug for this treatment arm (standard of care: heparins with optional GPI).

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Bivalirudin
    Reporting 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.

    Reporting group title
    Standard of Care: Heparins with optional GPI
    Reporting group description
    		 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.”

    Reporting group values
    		 Bivalirudin Standard of Care: Heparins with optional GPI Total
    Number of subjects
    		 1089 1109 2198
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0
        Newborns (0-27 days)
    		 0
        Infants and toddlers (28 days-23 months)
    		 0
        Children (2-11 years)
    		 0
        Adolescents (12-17 years)
    		 0
        Adults (18-64 years)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 61.4 ( 12.8 ) 62 ( 13.1 ) -
    Gender, Male/Female
    Units: participants
        Female
    		 275 248 523
        Male
    		 814 861 1675
    Region of Enrollment
    Units: Subjects
        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
    Units: Subjects
        Yes
    		 127 169 296
        No
    		 962 940 1902
    Medical history: Participant Is a Current Smoker (within past 30 days)
    Units: Subjects
        Yes
    		 453 472 925
        No
    		 636 637 1273
    Medical history: Participant Has Hypertension
    Units: Subjects
        Yes
    		 459 504 963
        No
    		 630 605 1235
    Medical history: Participant Has Hyperlipidemia
    Participant has known hyperlipidemia or is on lipid-lowering drugs
    Units: Subjects
        Yes
    		 398 417 815
        No
    		 691 692 1383
    Medical history: Participant Has Had Previous Myocardial Infarction (MI)
    Units: Subjects
        Yes
    		 80 113 193
        No
    		 1009 996 2005

    End points

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    End points reporting groups
    Reporting group title
    Bivalirudin
    Reporting 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.

    Reporting group title
    Standard of Care: Heparins with optional GPI
    Reporting group description
    		 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.”

    Primary: The Composite Incidence of Death and Non-coronary Artery Bypass Graft (CABG) Major Bleeding

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    End point title
    		 The Composite Incidence of Death and Non-coronary Artery Bypass Graft (CABG) Major Bleeding
    End point 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.
    End point type
    Primary
    End point timeframe
    Within 30 days
    End point values
    		 Bivalirudin Standard of Care: Heparins with optional GPI
    Number of subjects analysed
    1089
    1109
    Units: percentage of participants
        number (not applicable)
    5.1
    8.5
    Statistical analysis title
    		 Bivalirudin, Standard of Care 1
    Comparison groups
    Bivalirudin v Standard of Care: Heparins with optional GPI
    Number of subjects included in analysis
    2198
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0014
    Method
    		 Chi-squared
    Parameter type
    		 Relative Risk
    Point estimate
    0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.43
         upper limit
    		 0.82

    Secondary: The Composite Incidence of Death, Re-infarction (MI), or Non-CABG Major Bleeding

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    End point title
    		 The Composite Incidence of Death, Re-infarction (MI), or Non-CABG Major Bleeding
    End point 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. This was originally the study primary endpoint. The second protocol amendment (dated 24 April 2012) re-categorized this as a key secondary outcome.
    End point type
    Secondary
    End point timeframe
    Within 30 days
    End point values
    		 Bivalirudin Standard of Care: Heparins with optional GPI
    Number of subjects analysed
    1089
    1109
    Units: percentage of participants
        number (not applicable)
    6.6
    9.2
    Statistical analysis title
    		 Bivalirudin, Standard of Care 2
    Comparison groups
    Bivalirudin v Standard of Care: Heparins with optional GPI
    Number of subjects included in analysis
    2198
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.02
    Method
    		 Chi-squared
    Parameter type
    		 Relative Risk
    Point estimate
    0.72
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.54
         upper limit
    		 0.96

    Secondary: The Incidence of Death, Re-infarction, Non-CABG-related Major Bleeding, or Ischemia-driven Revascularization (IDR)

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    End point title
    		 The Incidence of Death, Re-infarction, Non-CABG-related Major Bleeding, or Ischemia-driven Revascularization (IDR)
    End point 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.
    End point type
    Secondary
    End point timeframe
    Within 30 days
    End point values
    		 Bivalirudin Standard of Care: Heparins with optional GPI
    Number of subjects analysed
    1089
    1109
    Units: percentage of participants
    number (not applicable)
        Death
    2.9
    3.1
        Re-infarction
    1.7
    0.9
        Non-CABG-related major bleeding
    2.6
    6
        IDR
    2.2
    1.5
    No statistical analyses for this end point

    Secondary: The Incidence of Death at 1 Year

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    End point title
    		 The Incidence of Death at 1 Year
    End point 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.
    End point type
    Secondary
    End point timeframe
    Within 1 Year
    End point values
    		 Bivalirudin Standard of Care: Heparins with optional GPI
    Number of subjects analysed
    1089
    1109
    Units: percentage of participants
        number (not applicable)
    5.4
    5.3
    No statistical analyses for this end point

    Secondary: The Incidence of Major bleeding: Thrombolysis in MI (TIMI) and Global Utilization of Streptokinase and tPA for Occluded Coronary Arteries (GUSTO)

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    End point title
    		 The Incidence of Major bleeding: Thrombolysis in MI (TIMI) and Global Utilization of Streptokinase and tPA for Occluded Coronary Arteries (GUSTO)
    End point 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.
    End point type
    Secondary
    End point timeframe
    Within 30 days
    End point values
    		 Bivalirudin Standard of Care: Heparins with optional GPI
    Number of subjects analysed
    1089
    1109
    Units: percentage of participants
    number (not applicable)
        Major bleeding: TIMI
    1.3
    2.1
        Major bleeding: GUSTO
    1.3
    2.3
    No statistical analyses for this end point

    Secondary: The Incidence of Minor Bleeding: TIMI and GUSTO

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    End point title
    		 The Incidence of Minor Bleeding: TIMI and GUSTO
    End point 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.
    End point type
    Secondary
    End point timeframe
    Within 30 days
    End point values
    		 Bivalirudin Standard of Care: Heparins with optional GPI
    Number of subjects analysed
    1089
    1109
    Units: percentage of participants
    number (not applicable)
        Minor bleeding: TIMI
    6.5
    11.2
        Minor bleeding: GUSTO
    6.5
    11
    No statistical analyses for this end point

    Secondary: The Incidence of Stent Thrombosis (Academic Research Consortium [ARC definition])

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    End point title
    		 The Incidence of Stent Thrombosis (Academic Research Consortium [ARC definition])
    End point 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.
    End point type
    Secondary
    End point timeframe
    Within 30 days
    End point values
    		 Bivalirudin Standard of Care: Heparins with optional GPI
    Number of subjects analysed
    1089
    1109
    Units: percentage of participants
        number (not applicable)
    1.6
    0.5
    No statistical analyses for this end point

    Secondary: The Incidence of Thrombocytopenia

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    End point title
    		 The Incidence of Thrombocytopenia
    End point 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.
    End point type
    Secondary
    End point timeframe
    Within 30 days
    End point values
    		 Bivalirudin Standard of Care: Heparins with optional GPI
    Number of subjects analysed
    1089
    1109
    Units: percentage of participants
        number (not applicable)
    0.7
    1.4
    No statistical analyses for this end point

    Secondary: The Incidence of Stroke

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    End point title
    		 The Incidence of Stroke
    End point 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.
    End point type
    Secondary
    End point timeframe
    Within 30 days
    End point values
    		 Bivalirudin Standard of Care: Heparins with optional GPI
    Number of subjects analysed
    1089
    1109
    Units: percentage of participants
        number (not applicable)
    0.6
    1
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From screening to Day 30
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    12.1
    Reporting groups
    Reporting group title
    Standard of Care: Heparins with optional GPI
    Reporting group description
    		 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.”

    Reporting group title
    Bivalirudin
    Reporting 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.

    Serious adverse events
    		 Standard of Care: Heparins with optional GPI Bivalirudin
    Total subjects affected by serious adverse events
         subjects affected / exposed
    129 / 1094 (11.79%)
    145 / 1099 (13.19%)
         number of deaths (all causes)
    32
    33
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Plasmacytoma
         subjects affected / exposed
    0 / 1094 (0.00%)
    1 / 1099 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic neoplasm
         subjects affected / exposed
    0 / 1094 (0.00%)
    1 / 1099 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Abdominal neoplasm
         subjects affected / exposed
    1 / 1094 (0.09%)
    0 / 1099 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Aortic dissection
         subjects affected / exposed
    0 / 1094 (0.00%)
    4 / 1099 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    2 / 1094 (0.18%)
    0 / 1099 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic stenosis
         subjects affected / exposed
    1 / 1094 (0.09%)
    1 / 1099 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reperfusion injury
         subjects affected / exposed
    0 / 1094 (0.00%)
    1 / 1099 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic aneurysm rupture
         subjects affected / exposed
    0 / 1094 (0.00%)
    2 / 1099 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Haemodynamic instability
         subjects affected / exposed
    0 / 1094 (0.00%)
    1 / 1099 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    1 / 1094 (0.09%)
    0 / 1099 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Circulatory collapse
         subjects affected / exposed
    0 / 1094 (0.00%)
    1 / 1099 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Multi-organ failure
         subjects affected / exposed
    0 / 1094 (0.00%)
    3 / 1099 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Chest pain
         subjects affected / exposed
    3 / 1094 (0.27%)
    5 / 1099 (0.45%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 1094 (0.09%)
    1 / 1099 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    1 / 1094 (0.09%)
    1 / 1099 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Sudden cardiac death
         subjects affected / exposed
    0 / 1094 (0.00%)
    1 / 1099 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Malaise
         subjects affected / exposed
    0 / 1094 (0.00%)
    1 / 1099 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest discomfort
         subjects affected / exposed
    0 / 1094 (0.00%)
    1 / 1099 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac death
         subjects affected / exposed
    1 / 1094 (0.09%)
    0 / 1099 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema
         subjects affected / exposed
    5 / 1094 (0.46%)
    3 / 1099 (0.27%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pulmonary oedema
         subjects affected / exposed
    1 / 1094 (0.09%)
    2 / 1099 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    1 / 1094 (0.09%)
    2 / 1099 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 1094 (0.09%)
    1 / 1099 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung disorder
         subjects affected / exposed
    2 / 1094 (0.18%)
    0 / 1099 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 1094 (0.09%)
    1 / 1099 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 1094 (0.09%)
    0 / 1099 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Orthopnoea
         subjects affected / exposed
    1 / 1094 (0.09%)
    0 / 1099 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laryngeal oedema
         subjects affected / exposed
    0 / 1094 (0.00%)
    1 / 1099 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea exertional
         subjects affected / exposed
    1 / 1094 (0.09%)
    0 / 1099 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Hallucination
         subjects affected / exposed
    1 / 1094 (0.09%)
    0 / 1099 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Arteriogram coronary
         subjects affected / exposed
    0 / 1094 (0.00%)
    1 / 1099 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Gastrointestinal injury
         subjects affected / exposed
    0 / 1094 (0.00%)
    1 / 1099 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Facial bones fracture
         subjects affected / exposed
    1 / 1094 (0.09%)
    0 / 1099 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Ventricular septal defect
         subjects affected / exposed
    0 / 1094 (0.00%)
    1 / 1099 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Ventricular fibrillation
         subjects affected / exposed
    28 / 1094 (2.56%)
    39 / 1099 (3.55%)
         occurrences causally related to treatment / all
    0 / 32
    2 / 40
         deaths causally related to treatment / all
    0 / 3
    0 / 1
    Cardiogenic shock
         subjects affected / exposed
    17 / 1094 (1.55%)
    21 / 1099 (1.91%)
         occurrences causally related to treatment / all
    0 / 17
    0 / 21
         deaths causally related to treatment / all
    0 / 6
    0 / 10
    Cardiac arrest
         subjects affected / exposed
    17 / 1094 (1.55%)
    7 / 1099 (0.64%)
         occurrences causally related to treatment / all
    0 / 18
    0 / 7
         deaths causally related to treatment / all
    0 / 8
    0 / 1
    Cardiac failure
         subjects affected / exposed
    10 / 1094 (0.91%)
    8 / 1099 (0.73%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 8
         deaths causally related to treatment / all
    0 / 3
    0 / 4
    Coronary artery dissection
         subjects affected / exposed
    2 / 1094 (0.18%)
    7 / 1099 (0.64%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    4 / 1094 (0.37%)
    3 / 1099 (0.27%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    3 / 1094 (0.27%)
    2 / 1099 (0.18%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    2 / 1094 (0.18%)
    3 / 1099 (0.27%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intracardiac thrombus
         subjects affected / exposed
    1 / 1094 (0.09%)
    3 / 1099 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    3 / 1094 (0.27%)
    2 / 1099 (0.18%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    2 / 1094 (0.18%)
    2 / 1099 (0.18%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery perforation
         subjects affected / exposed
    1 / 1094 (0.09%)
    2 / 1099 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular septal defect acquired
         subjects affected / exposed
    0 / 1094 (0.00%)
    2 / 1099 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Tachycardia
         subjects affected / exposed
    2 / 1094 (0.18%)
    0 / 1099 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary no-reflow phenomenon
         subjects affected / exposed
    1 / 1094 (0.09%)
    1 / 1099 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    2 / 1094 (0.18%)
    0 / 1099 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    0 / 1094 (0.00%)
    2 / 1099 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Atrioventricular block
         subjects affected / exposed
    0 / 1094 (0.00%)
    2 / 1099 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Acute myocardial infarction
         subjects affected / exposed
    2 / 1094 (0.18%)
    0 / 1099 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Ventricular extrasystoles
         subjects affected / exposed
    0 / 1094 (0.00%)
    1 / 1099 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular arrhythmia
         subjects affected / exposed
    1 / 1094 (0.09%)
    0 / 1099 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricle rupture
         subjects affected / exposed
    0 / 1094 (0.00%)
    1 / 1099 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Stress cardiomyopathy
         subjects affected / exposed
    0 / 1094 (0.00%)
    1 / 1099 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Sinus arrest
         subjects affected / exposed
    0 / 1094 (0.00%)
    1 / 1099 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sick sinus syndrome
         subjects affected / exposed
    0 / 1094 (0.00%)
    1 / 1099 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericarditis
         subjects affected / exposed
    0 / 1094 (0.00%)
    1 / 1099 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulseless electrical activity
         subjects affected / exposed
    1 / 1094 (0.09%)
    0 / 1099 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    0 / 1094 (0.00%)
    1 / 1099 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Papillary muscle rupture
         subjects affected / exposed
    1 / 1094 (0.09%)
    0 / 1099 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Palpitations
         subjects affected / exposed
    0 / 1094 (0.00%)
    1 / 1099 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 1094 (0.09%)
    0 / 1099 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Mitral valve incompetence
         subjects affected / exposed
    0 / 1094 (0.00%)
    1 / 1099 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Interventricular septum rupture
         subjects affected / exposed
    1 / 1094 (0.09%)
    0 / 1099 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure acute
         subjects affected / exposed
    1 / 1094 (0.09%)
    0 / 1099 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cardiac tamponade
         subjects affected / exposed
    0 / 1094 (0.00%)
    1 / 1099 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardiac disorder
         subjects affected / exposed
    0 / 1094 (0.00%)
    1 / 1099 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac asthma
         subjects affected / exposed
    0 / 1094 (0.00%)
    1 / 1099 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block second degree
         subjects affected / exposed
    0 / 1094 (0.00%)
    1 / 1099 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    1 / 1094 (0.09%)
    0 / 1099 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Syncope
         subjects affected / exposed
    0 / 1094 (0.00%)
    2 / 1099 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    0 / 1094 (0.00%)
    1 / 1099 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotonia
         subjects affected / exposed
    0 / 1094 (0.00%)
    1 / 1099 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    0 / 1094 (0.00%)
    1 / 1099 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Dizziness
         subjects affected / exposed
    1 / 1094 (0.09%)
    0 / 1099 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    1 / 1094 (0.09%)
    0 / 1099 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Gastrointestinal disorders
    Intestinal infarction
         subjects affected / exposed
    1 / 1094 (0.09%)
    1 / 1099 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Ileus
         subjects affected / exposed
    1 / 1094 (0.09%)
    0 / 1099 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    1 / 1094 (0.09%)
    0 / 1099 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal wall haemorrhage
         subjects affected / exposed
    0 / 1094 (0.00%)
    1 / 1099 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    0 / 1094 (0.00%)
    1 / 1099 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal failure acute
         subjects affected / exposed
    4 / 1094 (0.37%)
    4 / 1099 (0.36%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    0 / 1094 (0.00%)
    1 / 1099 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephropathy toxic
         subjects affected / exposed
    1 / 1094 (0.09%)
    0 / 1099 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Calculus urinary
         subjects affected / exposed
    1 / 1094 (0.09%)
    0 / 1099 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Compartment syndrome
         subjects affected / exposed
    0 / 1094 (0.00%)
    1 / 1099 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    5 / 1094 (0.46%)
    2 / 1099 (0.18%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 1094 (0.00%)
    3 / 1099 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Urinary tract infection
         subjects affected / exposed
    1 / 1094 (0.09%)
    1 / 1099 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 1094 (0.09%)
    0 / 1099 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pneumonia staphylococcal
         subjects affected / exposed
    0 / 1094 (0.00%)
    1 / 1099 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia haemophilus
         subjects affected / exposed
    0 / 1094 (0.00%)
    1 / 1099 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridial infection
         subjects affected / exposed
    1 / 1094 (0.09%)
    0 / 1099 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    1 / 1094 (0.09%)
    0 / 1099 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    1 / 1094 (0.09%)
    0 / 1099 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 2%
    Non-serious adverse events
    		 Standard of Care: Heparins with optional GPI Bivalirudin
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    119 / 1094 (10.88%)
    134 / 1099 (12.19%)
    Vascular disorders
    Hypotension
         subjects affected / exposed
    20 / 1094 (1.83%)
    22 / 1099 (2.00%)
         occurrences all number
    20
    24
    Cardiac disorders
    Ventricular tachycardia
         subjects affected / exposed
    39 / 1094 (3.56%)
    57 / 1099 (5.19%)
         occurrences all number
    40
    62
    Atrial fibrillation
         subjects affected / exposed
    35 / 1094 (3.20%)
    35 / 1099 (3.18%)
         occurrences all number
    35
    36
    Bradycardia
         subjects affected / exposed
    25 / 1094 (2.29%)
    20 / 1099 (1.82%)
         occurrences all number
    25
    21

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    16 Apr 2010
    This first protocol amendment, dated 16 April 2010, consisted of both clinical and administrative amendments. The clinical amendments are summarized below. -All endpoints except for mortality were removed from the one-year follow-up assessment. -Stroke was added as a secondary endpoint. -The Health Economics section was removed from the protocol. -Collection of C-reactive protein was removed from the protocol. -The text was clarified to indicate that AE/SAE collection was to commence as soon as consent had been given. -Approval of bivalirudin indication in the European Union (EU) for use in STEMI patients undergoing PCI was added. -Randomisation would only be done using the envelope method rather than a choice of interactive voice response system (IVRS) also.
    24 Apr 2012
    This second protocol amendment, dated 24 April 2012, consisted of both clinical and administrative amendments. The clinical amendments are summarized below. -The primary endpoint at 30 days was amended by removing re-infarction (MI). The original primary endpoint was the composite of death from any cause, re-infarction, or non-CABG major bleeding, which became the key secondary outcome after the change in the protocol. The change in the primary endpoint was made to reduce the sample size needed. The treatment effect of bivalirudin was assumed to come entirely from reductions in rates of death or major bleeding, With the anticipated null effect of the two study treatments on re-infarction, the decision to remove this component from the composite primary endpoint substantially reduced trial size to 2,200 subjects (from the initial 3,680 required with the triple composite), a more realistic enrollment goal. -Collection of glucose and HbA1c were removed from the protocol. -Collection of biomarkers 24 and 48 hours post-index procedure was removed from the protocol. -Collection of vital signs was removed from the protocol. An addendum to that amendment was made for Germany as the competent authority in Germany (BfArM) requested that all centres in Germany would continue to perform biomarker and ECG collection at 24 and 48 hours.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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