Trial Outcomes & Findings for European Ambulance Acute Coronary Syndrome (ACS) Angiography Trial (NCT NCT01087723)
NCT ID: NCT01087723
Last Updated: 2016-02-12
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
2198 participants
Primary outcome timeframe
Within 30 days
Results posted on
2016-02-12
Participant Flow
Participant milestones
| Measure |
Bivalirudin
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: Heparins With Optional GPI
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."
|
|---|---|---|
|
Overall Study
STARTED
|
1089
|
1109
|
|
Overall Study
Received at Least 1 Dose of Study Drug
|
1099
|
1094
|
|
Overall Study
COMPLETED
|
1075
|
1089
|
|
Overall Study
NOT COMPLETED
|
14
|
20
|
Reasons for withdrawal
| Measure |
Bivalirudin
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: Heparins With Optional GPI
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."
|
|---|---|---|
|
Overall Study
1 Year Visit Too Early (<335 days)
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
10
|
13
|
|
Overall Study
Physician Decision
|
2
|
0
|
|
Overall Study
Lost to Follow-up
|
1
|
4
|
|
Overall Study
Reason Not Specified
|
1
|
2
|
Baseline Characteristics
European Ambulance Acute Coronary Syndrome (ACS) Angiography Trial
Baseline characteristics by cohort
| Measure |
Bivalirudin
n=1089 Participants
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: Heparins With Optional GPI
n=1109 Participants
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
n=2198 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
61.4 years
STANDARD_DEVIATION 12.8 • n=5 Participants
|
62.0 years
STANDARD_DEVIATION 13.1 • n=7 Participants
|
61.7 years
STANDARD_DEVIATION 13.0 • n=5 Participants
|
|
Sex: Female, Male
Female
|
275 Participants
n=5 Participants
|
248 Participants
n=7 Participants
|
523 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
814 Participants
n=5 Participants
|
861 Participants
n=7 Participants
|
1675 Participants
n=5 Participants
|
|
Region of Enrollment
Austria
|
4 participants
n=5 Participants
|
5 participants
n=7 Participants
|
9 participants
n=5 Participants
|
|
Region of Enrollment
Czech Republic
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Region of Enrollment
Netherlands
|
377 participants
n=5 Participants
|
391 participants
n=7 Participants
|
768 participants
n=5 Participants
|
|
Region of Enrollment
Denmark
|
78 participants
n=5 Participants
|
72 participants
n=7 Participants
|
150 participants
n=5 Participants
|
|
Region of Enrollment
Poland
|
55 participants
n=5 Participants
|
56 participants
n=7 Participants
|
111 participants
n=5 Participants
|
|
Region of Enrollment
Italy
|
31 participants
n=5 Participants
|
41 participants
n=7 Participants
|
72 participants
n=5 Participants
|
|
Region of Enrollment
France
|
398 participants
n=5 Participants
|
397 participants
n=7 Participants
|
795 participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
139 participants
n=5 Participants
|
140 participants
n=7 Participants
|
279 participants
n=5 Participants
|
|
Region of Enrollment
Slovenia
|
7 participants
n=5 Participants
|
6 participants
n=7 Participants
|
13 participants
n=5 Participants
|
|
Medical history: Participant Has Diabetes
|
127 participants
n=5 Participants
|
169 participants
n=7 Participants
|
296 participants
n=5 Participants
|
|
Medical history: Participant Is a Current smoker (within past 30 days)
|
453 participants
n=5 Participants
|
472 participants
n=7 Participants
|
925 participants
n=5 Participants
|
|
Medical history: Participant Has Hypertension
|
459 participants
n=5 Participants
|
504 participants
n=7 Participants
|
963 participants
n=5 Participants
|
|
Medical history: Participant Has Hyperlipidemia
|
398 participants
n=5 Participants
|
417 participants
n=7 Participants
|
815 participants
n=5 Participants
|
|
Medical history: Participant Has Had Previous myocardial infarction (MI)
|
380 participants
n=5 Participants
|
113 participants
n=7 Participants
|
493 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Within 30 daysPopulation: Participants who were randomized and signed an ICF; ITT population
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.
Outcome measures
| Measure |
Bivalirudin
n=1089 Participants
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: Heparins With Optional GPI
n=1109 Participants
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."
|
|---|---|---|
|
The Composite Incidence of Death and Non-coronary Artery Bypass Graft (CABG) Major Bleeding
|
5.1 percentage of participants
|
8.5 percentage of participants
|
SECONDARY outcome
Timeframe: Within 30 daysPopulation: Participants who were randomized and signed an ICF; ITT population
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.
Outcome measures
| Measure |
Bivalirudin
n=1089 Participants
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: Heparins With Optional GPI
n=1109 Participants
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."
|
|---|---|---|
|
The Composite Incidence of Death, Re-infarction (MI), or Non-CABG Major Bleeding
|
6.6 percentage of participants
|
9.2 percentage of participants
|
SECONDARY outcome
Timeframe: Within 30 daysPopulation: Participants who were randomized and signed an ICF; ITT population
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.
Outcome measures
| Measure |
Bivalirudin
n=1089 Participants
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: Heparins With Optional GPI
n=1109 Participants
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."
|
|---|---|---|
|
The Incidence of Death, Re-infarction, Non-CABG-related Major Bleeding, or Ischemia-driven Revascularization (IDR)
Death
|
2.9 percentage of participants
|
3.1 percentage of participants
|
|
The Incidence of Death, Re-infarction, Non-CABG-related Major Bleeding, or Ischemia-driven Revascularization (IDR)
Re-infarction
|
1.7 percentage of participants
|
0.9 percentage of participants
|
|
The Incidence of Death, Re-infarction, Non-CABG-related Major Bleeding, or Ischemia-driven Revascularization (IDR)
Non-CABG-related major bleeding
|
2.6 percentage of participants
|
6.0 percentage of participants
|
|
The Incidence of Death, Re-infarction, Non-CABG-related Major Bleeding, or Ischemia-driven Revascularization (IDR)
IDR
|
2.2 percentage of participants
|
1.5 percentage of participants
|
SECONDARY outcome
Timeframe: Within 1 YearPopulation: Participants who were randomized and signed an ICF; ITT population
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.
Outcome measures
| Measure |
Bivalirudin
n=1089 Participants
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: Heparins With Optional GPI
n=1109 Participants
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."
|
|---|---|---|
|
The Incidence of Death at 1 Year
|
5.4 percentage of participants
|
5.3 percentage of participants
|
SECONDARY outcome
Timeframe: Within 30 daysPopulation: Participants who were randomized and signed an ICF; ITT population
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.
Outcome measures
| Measure |
Bivalirudin
n=1089 Participants
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: Heparins With Optional GPI
n=1109 Participants
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."
|
|---|---|---|
|
The Incidence of Major Bleeding: Thrombolysis in MI (TIMI) and Global Utilization of Streptokinase and tPA for Occluded Coronary Arteries (GUSTO)
Major bleeding: TIMI
|
1.3 percentage of participants
|
2.1 percentage of participants
|
|
The Incidence of Major Bleeding: Thrombolysis in MI (TIMI) and Global Utilization of Streptokinase and tPA for Occluded Coronary Arteries (GUSTO)
Major bleeding: GUSTO
|
1.3 percentage of participants
|
2.3 percentage of participants
|
SECONDARY outcome
Timeframe: Within 30 daysPopulation: Participants who were randomized and signed an ICF; ITT population
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.
Outcome measures
| Measure |
Bivalirudin
n=1089 Participants
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: Heparins With Optional GPI
n=1109 Participants
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."
|
|---|---|---|
|
The Incidence of Minor Bleeding: TIMI and GUSTO
Minor bleeding: TIMI
|
6.5 percentage of participants
|
11.2 percentage of participants
|
|
The Incidence of Minor Bleeding: TIMI and GUSTO
Minor bleeding: GUSTO
|
6.5 percentage of participants
|
11.0 percentage of participants
|
SECONDARY outcome
Timeframe: Within 30 daysPopulation: Participants who were randomized and signed an ICF; ITT population
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.
Outcome measures
| Measure |
Bivalirudin
n=1089 Participants
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: Heparins With Optional GPI
n=1109 Participants
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."
|
|---|---|---|
|
The Incidence of Stent Thrombosis (Academic Research Consortium [ARC Definition])
|
1.6 percentage of participants
|
0.5 percentage of participants
|
SECONDARY outcome
Timeframe: Within 30 daysPopulation: Participants who were randomized and signed an ICF; ITT population
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.
Outcome measures
| Measure |
Bivalirudin
n=1089 Participants
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: Heparins With Optional GPI
n=1109 Participants
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."
|
|---|---|---|
|
The Incidence of Thrombocytopenia
|
0.7 percentage of participants
|
1.4 percentage of participants
|
SECONDARY outcome
Timeframe: Within 30 daysPopulation: Participants who were randomized and signed an ICF; ITT population
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.
Outcome measures
| Measure |
Bivalirudin
n=1089 Participants
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: Heparins With Optional GPI
n=1109 Participants
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."
|
|---|---|---|
|
The Incidence of Stroke
|
0.6 percentage of participants
|
1.0 percentage of participants
|
Adverse Events
Bivalirudin
Serious events: 145 serious events
Other events: 134 other events
Deaths: 0 deaths
Standard of Care: Heparins With Optional GPI
Serious events: 129 serious events
Other events: 119 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Bivalirudin
n=1099 participants at risk
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: Heparins With Optional GPI
n=1094 participants at risk
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."
|
|---|---|---|
|
Cardiac disorders
Stress cardiomyopathy
|
0.09%
1/1099 • From screening to Day 30
|
0.00%
0/1094 • From screening to Day 30
|
|
Injury, poisoning and procedural complications
Gastrointestinal injury
|
0.09%
1/1099 • From screening to Day 30
|
0.00%
0/1094 • From screening to Day 30
|
|
Injury, poisoning and procedural complications
Facial bones fracture
|
0.00%
0/1099 • From screening to Day 30
|
0.09%
1/1094 • From screening to Day 30
|
|
Investigations
Arteriogram coronary
|
0.09%
1/1099 • From screening to Day 30
|
0.00%
0/1094 • From screening to Day 30
|
|
Musculoskeletal and connective tissue disorders
Compartment syndrome
|
0.09%
1/1099 • From screening to Day 30
|
0.00%
0/1094 • From screening to Day 30
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Plasmacytoma
|
0.09%
1/1099 • From screening to Day 30
|
0.00%
0/1094 • From screening to Day 30
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic neoplasm
|
0.09%
1/1099 • From screening to Day 30
|
0.00%
0/1094 • From screening to Day 30
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Abdominal neoplasm
|
0.00%
0/1099 • From screening to Day 30
|
0.09%
1/1094 • From screening to Day 30
|
|
Nervous system disorders
Syncope
|
0.18%
2/1099 • From screening to Day 30
|
0.00%
0/1094 • From screening to Day 30
|
|
Nervous system disorders
Presyncope
|
0.09%
1/1099 • From screening to Day 30
|
0.00%
0/1094 • From screening to Day 30
|
|
Nervous system disorders
Ischaemic stroke
|
0.09%
1/1099 • From screening to Day 30
|
0.00%
0/1094 • From screening to Day 30
|
|
Nervous system disorders
Hypotonia
|
0.09%
1/1099 • From screening to Day 30
|
0.00%
0/1094 • From screening to Day 30
|
|
Nervous system disorders
Dizziness
|
0.00%
0/1099 • From screening to Day 30
|
0.09%
1/1094 • From screening to Day 30
|
|
Nervous system disorders
Cerebral infarction
|
0.00%
0/1099 • From screening to Day 30
|
0.09%
1/1094 • From screening to Day 30
|
|
Psychiatric disorders
Hallucination
|
0.00%
0/1099 • From screening to Day 30
|
0.09%
1/1094 • From screening to Day 30
|
|
Renal and urinary disorders
Renal failure acute
|
0.36%
4/1099 • From screening to Day 30
|
0.37%
4/1094 • From screening to Day 30
|
|
Renal and urinary disorders
Renal failure
|
0.09%
1/1099 • From screening to Day 30
|
0.00%
0/1094 • From screening to Day 30
|
|
Renal and urinary disorders
Nephropathy toxic
|
0.00%
0/1099 • From screening to Day 30
|
0.09%
1/1094 • From screening to Day 30
|
|
Renal and urinary disorders
Calculus urinary
|
0.00%
0/1099 • From screening to Day 30
|
0.09%
1/1094 • From screening to Day 30
|
|
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema
|
0.27%
3/1099 • From screening to Day 30
|
0.46%
5/1094 • From screening to Day 30
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.18%
2/1099 • From screening to Day 30
|
0.09%
1/1094 • From screening to Day 30
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.18%
2/1099 • From screening to Day 30
|
0.09%
1/1094 • From screening to Day 30
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.09%
1/1099 • From screening to Day 30
|
0.09%
1/1094 • From screening to Day 30
|
|
Respiratory, thoracic and mediastinal disorders
Lung disorder
|
0.00%
0/1099 • From screening to Day 30
|
0.18%
2/1094 • From screening to Day 30
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.09%
1/1099 • From screening to Day 30
|
0.09%
1/1094 • From screening to Day 30
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/1099 • From screening to Day 30
|
0.09%
1/1094 • From screening to Day 30
|
|
Respiratory, thoracic and mediastinal disorders
Orthopnoea
|
0.00%
0/1099 • From screening to Day 30
|
0.09%
1/1094 • From screening to Day 30
|
|
Respiratory, thoracic and mediastinal disorders
Laryngeal oedema
|
0.09%
1/1099 • From screening to Day 30
|
0.00%
0/1094 • From screening to Day 30
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
0.00%
0/1099 • From screening to Day 30
|
0.09%
1/1094 • From screening to Day 30
|
|
Vascular disorders
Aortic dissection
|
0.36%
4/1099 • From screening to Day 30
|
0.00%
0/1094 • From screening to Day 30
|
|
Vascular disorders
Hypotension
|
0.00%
0/1099 • From screening to Day 30
|
0.18%
2/1094 • From screening to Day 30
|
|
Vascular disorders
Aortic stenosis
|
0.09%
1/1099 • From screening to Day 30
|
0.09%
1/1094 • From screening to Day 30
|
|
Vascular disorders
Aortic aneurysm rupture
|
0.18%
2/1099 • From screening to Day 30
|
0.00%
0/1094 • From screening to Day 30
|
|
Vascular disorders
Reperfusion injury
|
0.09%
1/1099 • From screening to Day 30
|
0.00%
0/1094 • From screening to Day 30
|
|
Vascular disorders
Hypertensive crisis
|
0.00%
0/1099 • From screening to Day 30
|
0.09%
1/1094 • From screening to Day 30
|
|
Vascular disorders
Haemodynamic instability
|
0.09%
1/1099 • From screening to Day 30
|
0.00%
0/1094 • From screening to Day 30
|
|
Vascular disorders
Circulatory collapse
|
0.09%
1/1099 • From screening to Day 30
|
0.00%
0/1094 • From screening to Day 30
|
|
Cardiac disorders
Papillary muscle rupture
|
0.00%
0/1099 • From screening to Day 30
|
0.09%
1/1094 • From screening to Day 30
|
|
Cardiac disorders
Palpitations
|
0.09%
1/1099 • From screening to Day 30
|
0.00%
0/1094 • From screening to Day 30
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/1099 • From screening to Day 30
|
0.09%
1/1094 • From screening to Day 30
|
|
Cardiac disorders
Mitral valve incompetence
|
0.09%
1/1099 • From screening to Day 30
|
0.00%
0/1094 • From screening to Day 30
|
|
Cardiac disorders
Interventricular septum rupture
|
0.00%
0/1099 • From screening to Day 30
|
0.09%
1/1094 • From screening to Day 30
|
|
Cardiac disorders
Cardiac tamponade
|
0.09%
1/1099 • From screening to Day 30
|
0.00%
0/1094 • From screening to Day 30
|
|
Cardiac disorders
Cardiac failure acute
|
0.00%
0/1099 • From screening to Day 30
|
0.09%
1/1094 • From screening to Day 30
|
|
Cardiac disorders
Cardiac disorder
|
0.09%
1/1099 • From screening to Day 30
|
0.00%
0/1094 • From screening to Day 30
|
|
Cardiac disorders
Cardiac asthma
|
0.09%
1/1099 • From screening to Day 30
|
0.00%
0/1094 • From screening to Day 30
|
|
Cardiac disorders
Atrioventricular block second degree
|
0.09%
1/1099 • From screening to Day 30
|
0.00%
0/1094 • From screening to Day 30
|
|
Cardiac disorders
Angina unstable
|
0.00%
0/1099 • From screening to Day 30
|
0.09%
1/1094 • From screening to Day 30
|
|
Congenital, familial and genetic disorders
Ventricular septal defect
|
0.09%
1/1099 • From screening to Day 30
|
0.00%
0/1094 • From screening to Day 30
|
|
Gastrointestinal disorders
Intestinal infarction
|
0.09%
1/1099 • From screening to Day 30
|
0.09%
1/1094 • From screening to Day 30
|
|
Gastrointestinal disorders
Ileus
|
0.00%
0/1099 • From screening to Day 30
|
0.09%
1/1094 • From screening to Day 30
|
|
Gastrointestinal disorders
Abdominal wall haemorrhage
|
0.09%
1/1099 • From screening to Day 30
|
0.00%
0/1094 • From screening to Day 30
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/1099 • From screening to Day 30
|
0.09%
1/1094 • From screening to Day 30
|
|
General disorders
Chest pain
|
0.45%
5/1099 • From screening to Day 30
|
0.27%
3/1094 • From screening to Day 30
|
|
General disorders
Multi-organ failure
|
0.27%
3/1099 • From screening to Day 30
|
0.00%
0/1094 • From screening to Day 30
|
|
General disorders
Non-cardiac chest pain
|
0.09%
1/1099 • From screening to Day 30
|
0.09%
1/1094 • From screening to Day 30
|
|
General disorders
Death
|
0.09%
1/1099 • From screening to Day 30
|
0.09%
1/1094 • From screening to Day 30
|
|
General disorders
Sudden cardiac death
|
0.09%
1/1099 • From screening to Day 30
|
0.00%
0/1094 • From screening to Day 30
|
|
General disorders
Malaise
|
0.09%
1/1099 • From screening to Day 30
|
0.00%
0/1094 • From screening to Day 30
|
|
General disorders
Chest discomfort
|
0.09%
1/1099 • From screening to Day 30
|
0.00%
0/1094 • From screening to Day 30
|
|
Cardiac disorders
Sinus arrest
|
0.09%
1/1099 • From screening to Day 30
|
0.00%
0/1094 • From screening to Day 30
|
|
Cardiac disorders
Sick sinus syndrome
|
0.09%
1/1099 • From screening to Day 30
|
0.00%
0/1094 • From screening to Day 30
|
|
General disorders
Cardiac death
|
0.00%
0/1099 • From screening to Day 30
|
0.09%
1/1094 • From screening to Day 30
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.09%
1/1099 • From screening to Day 30
|
0.00%
0/1094 • From screening to Day 30
|
|
Infections and infestations
Pneumonia
|
0.18%
2/1099 • From screening to Day 30
|
0.46%
5/1094 • From screening to Day 30
|
|
Infections and infestations
Septic shock
|
0.27%
3/1099 • From screening to Day 30
|
0.00%
0/1094 • From screening to Day 30
|
|
Infections and infestations
Urinary tract infection
|
0.09%
1/1099 • From screening to Day 30
|
0.09%
1/1094 • From screening to Day 30
|
|
Infections and infestations
Sepsis
|
0.00%
0/1099 • From screening to Day 30
|
0.09%
1/1094 • From screening to Day 30
|
|
Infections and infestations
Pneumonia staphylococcal
|
0.09%
1/1099 • From screening to Day 30
|
0.00%
0/1094 • From screening to Day 30
|
|
Infections and infestations
Pneumonia haemophilus
|
0.09%
1/1099 • From screening to Day 30
|
0.00%
0/1094 • From screening to Day 30
|
|
Infections and infestations
Clostridial infection
|
0.00%
0/1099 • From screening to Day 30
|
0.09%
1/1094 • From screening to Day 30
|
|
Infections and infestations
Bronchitis
|
0.00%
0/1099 • From screening to Day 30
|
0.09%
1/1094 • From screening to Day 30
|
|
Infections and infestations
Appendicitis
|
0.00%
0/1099 • From screening to Day 30
|
0.09%
1/1094 • From screening to Day 30
|
|
Cardiac disorders
Pulseless electrical activity
|
0.00%
0/1099 • From screening to Day 30
|
0.09%
1/1094 • From screening to Day 30
|
|
Cardiac disorders
Pericarditis
|
0.09%
1/1099 • From screening to Day 30
|
0.00%
0/1094 • From screening to Day 30
|
|
Cardiac disorders
Pericardial effusion
|
0.09%
1/1099 • From screening to Day 30
|
0.00%
0/1094 • From screening to Day 30
|
|
Cardiac disorders
Atrioventricular block
|
0.18%
2/1099 • From screening to Day 30
|
0.00%
0/1094 • From screening to Day 30
|
|
Cardiac disorders
Acute myocardial infarction
|
0.00%
0/1099 • From screening to Day 30
|
0.18%
2/1094 • From screening to Day 30
|
|
Cardiac disorders
Ventricular extrasystoles
|
0.09%
1/1099 • From screening to Day 30
|
0.00%
0/1094 • From screening to Day 30
|
|
Cardiac disorders
Ventricular arrhythmia
|
0.00%
0/1099 • From screening to Day 30
|
0.09%
1/1094 • From screening to Day 30
|
|
Cardiac disorders
Ventricle rupture
|
0.09%
1/1099 • From screening to Day 30
|
0.00%
0/1094 • From screening to Day 30
|
|
Cardiac disorders
Ventricular fibrillation
|
3.5%
39/1099 • From screening to Day 30
|
2.6%
28/1094 • From screening to Day 30
|
|
Cardiac disorders
Cardiogenic shock
|
1.9%
21/1099 • From screening to Day 30
|
1.6%
17/1094 • From screening to Day 30
|
|
Cardiac disorders
Cardiac arrest
|
0.64%
7/1099 • From screening to Day 30
|
1.6%
17/1094 • From screening to Day 30
|
|
Cardiac disorders
Cardiac failure
|
0.73%
8/1099 • From screening to Day 30
|
0.91%
10/1094 • From screening to Day 30
|
|
Cardiac disorders
Coronary artery dissection
|
0.64%
7/1099 • From screening to Day 30
|
0.18%
2/1094 • From screening to Day 30
|
|
Cardiac disorders
Ventricular tachycardia
|
0.27%
3/1099 • From screening to Day 30
|
0.37%
4/1094 • From screening to Day 30
|
|
Cardiac disorders
Bradycardia
|
0.18%
2/1099 • From screening to Day 30
|
0.27%
3/1094 • From screening to Day 30
|
|
Cardiac disorders
Atrioventricular block complete
|
0.27%
3/1099 • From screening to Day 30
|
0.18%
2/1094 • From screening to Day 30
|
|
Cardiac disorders
Angina pectoris
|
0.18%
2/1099 • From screening to Day 30
|
0.27%
3/1094 • From screening to Day 30
|
|
Cardiac disorders
Intracardiac thrombus
|
0.27%
3/1099 • From screening to Day 30
|
0.09%
1/1094 • From screening to Day 30
|
|
Cardiac disorders
Atrial fibrillation
|
0.18%
2/1099 • From screening to Day 30
|
0.18%
2/1094 • From screening to Day 30
|
|
Cardiac disorders
Coronary artery perforation
|
0.18%
2/1099 • From screening to Day 30
|
0.09%
1/1094 • From screening to Day 30
|
|
Cardiac disorders
Ventricular septal defect acquired
|
0.18%
2/1099 • From screening to Day 30
|
0.00%
0/1094 • From screening to Day 30
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/1099 • From screening to Day 30
|
0.18%
2/1094 • From screening to Day 30
|
|
Cardiac disorders
Coronary no-reflow phenomenon
|
0.09%
1/1099 • From screening to Day 30
|
0.09%
1/1094 • From screening to Day 30
|
|
Cardiac disorders
Coronary artery stenosis
|
0.00%
0/1099 • From screening to Day 30
|
0.18%
2/1094 • From screening to Day 30
|
|
Cardiac disorders
Cardio-respiratory arrest
|
0.18%
2/1099 • From screening to Day 30
|
0.00%
0/1094 • From screening to Day 30
|
Other adverse events
| Measure |
Bivalirudin
n=1099 participants at risk
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: Heparins With Optional GPI
n=1094 participants at risk
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."
|
|---|---|---|
|
Cardiac disorders
Ventricular tachycardia
|
5.2%
57/1099 • From screening to Day 30
|
3.6%
39/1094 • From screening to Day 30
|
|
Cardiac disorders
Atrial fibrillation
|
3.2%
35/1099 • From screening to Day 30
|
3.2%
35/1094 • From screening to Day 30
|
|
Cardiac disorders
Bradycardia
|
1.8%
20/1099 • From screening to Day 30
|
2.3%
25/1094 • From screening to Day 30
|
|
Vascular disorders
Hypotension
|
2.0%
22/1099 • From screening to Day 30
|
1.8%
20/1094 • From screening to Day 30
|
Additional Information
Global Health Science Center
The Medicines Company
Phone: 800-388-1183
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60