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

• Sponsor: The Medicines Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01087723
• Collaborator: (none)
• Enrollment: 2,198
• Locations: 145
• Arms: 2
• Duration (Months): 53
• Patients Per Site: 15.2
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Coronary Syndrome	Drug: Bivalirudin; Drug: Heparin	Phase 3

Detailed Description

The purpose of the trial is to show that the early administration of bivalirudin improves 30-day outcomes when compared to the current standard of care in participants with STE-ACS, with an onset of symptoms of >20 minutes and <12 hours, intended for a primary PCI management strategy, presenting either via ambulance or to centers where PCI is not performed.

All participants are to receive treatment with aspirin (150-325 milligrams [mg] administered orally or 250-500 mg intravenously [IV]), followed by 75-100 milligrams/day (mg/day) for at least 1 year and a loading dose of an approved P2Y12 receptor blocker, such as clopidogrel, prasugrel, or ticagrelor, that was to be continued as per European Society of Cardiology guidelines (preferably for 1 year) in all participants.

The primary objectives of the trial are to show that, when compared with standard anti-thrombotic therapies other than bivalirudin (which includes treatment with unfractionated heparin [UFH] and optional glycoprotein IIb/IIIa inhibitor [GPI]) that at 30 days:

• Bivalirudin is superior to control at reducing a composite of death and non-coronary artery bypass graft (CABG)-related protocol major bleeding.

Study Design

• Study Type: Interventional
• Actual Enrollment: 2198 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Multi-centre, Multi-national, Prospective, Randomised, Open-label, Comparison of Bivalirudin to Other Guideline Based Current Therapies (Excluding Bivalirudin)
• Study Start Date: Mar 1, 2010
• Actual Primary Completion Date: Aug 1, 2013
• Actual Study Completion Date: Aug 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bivalirudin 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.	Drug: Bivalirudin; Other Names: Angiox Angiomax
Active Comparator: 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 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."	Drug: Heparin; Other Names: UFH LMWH

Outcome Measures

Primary Outcome Measures

1. The Composite Incidence of Death and Non-coronary Artery Bypass Graft (CABG) Major Bleeding [Within 30 days]

   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.

Secondary Outcome Measures

1. The Composite Incidence of Death, Re-infarction (MI), or Non-CABG Major Bleeding [Within 30 days]

   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.

2. The Incidence of Death, Re-infarction, Non-CABG-related Major Bleeding, or Ischemia-driven Revascularization (IDR) [Within 30 days]

   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.

3. The Incidence of Death at 1 Year [Within 1 Year]

   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.

4. The Incidence of Major Bleeding: Thrombolysis in MI (TIMI) and Global Utilization of Streptokinase and tPA for Occluded Coronary Arteries (GUSTO) [Within 30 days]

   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.

5. The Incidence of Minor Bleeding: TIMI and GUSTO [Within 30 days]

   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.

6. The Incidence of Stent Thrombosis (Academic Research Consortium [ARC Definition]) [Within 30 days]

   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.

7. The Incidence of Thrombocytopenia [Within 30 days]

   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.

8. The Incidence of Stroke [Within 30 days]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

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 all of the following criteria:

1. Provided written informed consent before initiation of any study related procedures. Participants randomized in the ambulance may initially have signed an abridged version.

2. Aged ≥18 years at the time of randomization.

3. Had a presumed diagnosis of STE-ACS with onset of symptoms of >20 minutes and <12 hours with one or more of the following:

• ST segment elevation of ≥1 millimeters (mm) in ≥2 contiguous leads

• Presumably new left bundle branch block

• An infero-lateral myocardial infarction with ST segment depression of ≥1 mm in ≥2 of leads V1-3 with a positive terminal T wave

1. All participants would proceed with emergent angiography and primary PCI if indicated <2 hours after first medical contact

Exclusion Criteria:

Participants were excluded from the study if any of the following exclusion criteria applied prior to randomization:

1. Any bleeding diathesis or severe hematological disease or history of intra-cerebral mass, aneurysm, arterio-venous malformation, hemorrhagic stroke, intra-cranial hemorrhage, or gastrointestinal or genitourinary bleeding within the last 2 weeks.

2. Participants who had undergone recent surgery (including biopsy) within the last 2 weeks.

3. Participants who were on warfarin (not applicable if International Normalized Ratio known to be <1.5).

4. Participants who had received UFH, LMWH, or bivalirudin immediately before randomization.

5. Thrombolytic therapy within the last 48 hours.

6. Absolute contra-indications or allergy that could not be pre-medicated to iodinated contrast or to any of the study medications including aspirin or clopidogrel.

7. Contraindications to angiography, including but not limited to severe peripheral vascular disease.

8. If it was known, pregnant or nursing mothers. Women of child-bearing age were asked if they were pregnant or thought that they may be pregnant.

9. If it is known, a creatinine clearance <30 milliliter/minute or dialysis dependent.

10. Previous enrolment in this study.

11. Treatment with other investigational drugs or devices within the 30 days preceding randomization or planned use of other investigational drugs or devices in this trial.

12. Participants may not have been enrolled if the duration of randomized investigational medicinal product anti-thrombin infusion was likely to be <30 minutes from the time of onset to the commencement of angiography.

13. Participants may not have been enrolled within a primary PCI-capable hospital (unless at the time of randomization, the catheter laboratory was not available, and the participant required transfer to another primary PCI capable hospital).

14. Estimated body weight of >120 kg

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hanusch Krankenhaus	Wien		Austria
2	Magistratsabeilung 70, Wiener	Wien		Austria
3	Universitats-Klinik Fur	Wien		Austria
4	Wilhelminenspital MA 6 - BA 19	Wien		Austria
5	Zdravotnicka Zachranna Sluzba	Ceske Budejovice		Czech Republic
6	Aarhus Universitetshospital	Aarhus		Denmark
7	Akutlaegebil Kobenhavn, Hc Andersens Boulevard 23	Copenhagen		Denmark
8	Rigshospitalet	Copenhagen		Denmark
9	Gentofte Hospital	Hellerup		Denmark
10	Akutlaegebil Nordsjaelland	Hillerod		Denmark
11	Laegeambulancen Odense	Odense		Denmark
12	Odense Universitets Hospital	Odense		Denmark
13	Hopital Europeen Paris La Roseraie	Aubervilliers		France
14	Hospital Avicenne, Pharmacie -Gestion Des Essais Cliniques	Bobigny		France
15	Chu De Bordeaux - Hopital Pellegrin	Bordeaux Cedex		France
16	Centre Hospitalier Bourg En Bresse	Bourg En Bresse		France
17	Clinique Convert	Bourg En Bresse		France
18	Ch Jacques Coeur	Bourges		France
19	Centre Hospitalier Universitaire De Caen	Caen		France
20	Hopital Prive Saint Martin	Caen		France
21	Service De Cardiologie	Cedex		France
22	Ch Chateauroux	Chateauroux		France
23	Chu Clermont-Ferrand, Hopital	Clermont Ferrand		France
24	Samu-Smur Chu Clermont-Ferrand	Clermont Ferrand		France
25	Hopital Beaujon	Clichy		France
26	Ch Sud Francilien - Site Corbeil	Corbeil Essonne		France
27	Ch Sud Francilien - Site Corbeil, Pharmacie	Corbeil-Essonnes Cedex		France
28	Capio - Clinique Des Cedres	Cornebarrieu		France
29	Hospital Henri Mondor, Pharmacie	Creteil		France
30	Samu 92 Hauts De Seine	Garches		France
31	Clinique Les Eaux Claires Ghm	Grenoble		France
32	Chu A Michallon Grenoble	La Tronche		France
33	Samu Chu A Michallon Grenoble	La Tronche		France
34	Hopital Andre Mignot - Centre Hospitalier De Versailles	Le Chesnay Cedex		France
35	Chr Lille	Lille		France
36	Samu 59/Samu Du Nord	Lille		France
37	Centre Hospitalier De Longjumeau	Longjumeau		France
38	Centre Hospitalier St Joseph St Luc	Lyon		France
39	Institut Hospitalier Jacques Cartier	Massy		France
40	Centre Hospitalier De Montelimar	Montelimar		France
41	Chi Le Raincy - Montfermeil Site De Montfermeil	Montfermeil		France
42	Clinique Ambroise Pare	Neuilly		France
43	Centre Hospitalier	Paris		France
44	Hopital Bichat Claude Bernard	Paris		France
45	Hopital Europeen Georges Pompidou	Paris		France
46	Ch De Pau Hopital Francois Mitterand	Pau		France
47	Samu Ch De Pau	Pau		France
48	Cardiologic Hospital - Coronary Care Unit, University of Bordeaux	Pessac		France
49	Pole Smur, Samu 77 - Medecine	Seine et Marne		France
50	Clinique Belledonne	St Martin D Heres		France
51	Chu De Toulouse - Hopital Paule De Viguier	Toulouse		France
52	Chu Toulouse - Hopital Rangueil	Toulouse		France
53	Clinique Pasteur	Toulouse		France
54	Polyclinique Du Parc	Toulouse		France
55	Centre Hospitalier De Valence	Valence		France
56	Centre Hospitalier De Vienne Centre Hospitalier Lucien Hussel	Vienne		France
57	Kerckhoff Heart Center	Bad Nauheim		Germany
58	Rettungsdienst Wetteraukreis	Bad Nauheim		Germany
59	Charite Universitatsmedizin Berlin Campus Virchow-Klinikum	Berlin		Germany
60	Lutzowstrabe	Berlin		Germany
61	Sana Klinikum Lichtenberg Oskar Ziethen Krankenhaus, Fanningerstrasse 32	Berlin		Germany
62	Universitatsklinikum Benjamin Franklin, Hindenburgdamm 30	Berlin		Germany
63	Klinikum Links Der Weser	Bremen		Germany
64	Evangelisches Bethesda Johanniter	Duisburg		Germany
65	Feuerwehr Duisburg	Duisburg		Germany
66	Herzzentrum Duisburg, Klinik Fur Kardiologie And Angiologie	Duisburg		Germany
67	Klinikum Duisburg Ggmbh	Duisburg		Germany
68	Klinikum Der Johann Wolfgang Goethe Universitat	Frankfurt		Germany
69	Medizinische Hochschule Hannover, Carl Neuberg Str. 1	Hannover		Germany
70	Klinikum Ludwigshafen	Ludwigshafen		Germany
71	Stadtisches Klinikum Luneburg, Bogelstr. 1	Luneburg		Germany
72	Helios Klinik Der Universitat Witten Herdecke	Wuppertal		Germany
73	Ospedale Maggiore	Bologna		Italy
74	Ospedle Di Bentivoglio	Bologna		Italy
75	Policlinico S.Orsola Malpighi	Bologna		Italy
76	Ospedale Di Assisi	Perugia		Italy
77	Ospedale Di Castiglione Del Lago	Perugia		Italy
78	Ospedale Di Todi	Perugia		Italy
79	Ospedale S.Maria Misericordia	Perugia		Italy
80	Asur Marche- Zona 1 Pesaro	Pesaro		Italy
81	Azienda Ospedaliera San Salvatore	Pesaro		Italy
82	Emergency Rescue & Mobile Als Unit, Lanciarini Pub	Pesaro		Italy
83	Betreft Research Regional	Amersfoort		Netherlands
84	Meander Medisch Centrum	Amersfoort		Netherlands
85	Rav Noord En Oost Gelderland	Amersfoort		Netherlands
86	Pharmacy Department	Nieuwegein		Netherlands
87	Regional Ambulance Service Gelderland Midden	Nieuwegein		Netherlands
88	St Antonius Ziekenhuis	Nieuwegein		Netherlands
89	Service Gelderland-Zuid Klinisch Geneesmiddelonderzoek Klinsche Farmacie Afd Klinsche Farmacie	Nijmegan		Netherlands
90	Cwz Klinisch Geneesmiddelonderzoek Klinische	Nijmegen		Netherlands
91	Kgo Team Regional Ambulance	Nijmegen		Netherlands
92	Regional Ambulance Service Gelderland Zuid	Nijmegen		Netherlands
93	Regional Ambulance Service Gelderland-Zuid Distributiecentrum	Nijmegen		Netherlands
94	Regional Ambulance Service	Nijmegen		Netherlands
95	Umc St.Radboud Nijmegen	Nijmegen		Netherlands
96	Department Of Cardiology	Utrecht		Netherlands
97	Umc Utrecht	Utrecht		Netherlands
98	Isala Klinieken	Zwolle		Netherlands
99	Tav Trial Team, Isala Klinieken Ioc Weezenlanden Afd	Zwolle		Netherlands
100	Poradnia Kardiologiczna	Bedzin		Poland
101	Malopolskie Centrum Sercowo	Chrzanow		Poland
102	Szpital Powiatowy W Chrzanowie	Chrzanow		Poland
103	Oddzial Polskiej-Amerikanskiej Kliniki Serca	Dabrowa Gornicza		Poland
104	Szpital Powiatowy W Debicy	Debica		Poland
105	Specialist Hospital Gorlice	Gorlice		Poland
106	Szpital Powiatowy Im. Jana Pawla Ii W Kolbuszowej	Kolbuszowa		Poland
107	Jagiellonian University Medical College,	Krakow		Poland
108	Krakowskie Centrum	Krakow		Poland
109	Oddzial Kardiologii	Krakow		Poland
110	Samodzielny Publiczny Zaklad Opieki	Krakow		Poland
111	Szpital Specjalistyczny Im Szpitalny Oddzial Ratunkowy	Krakow		Poland
112	Spzoz Szpital Im. J.Dietla W Krynicy Zdroj	Krynica Zdroj		Poland
113	Spzoz Lask	Lask		Poland
114	Szpital Powiatowy W Limanowej	Limanowa		Poland
115	Szpital Bieganskiego	Lodz		Poland
116	Medical University Of Lublin	Lublin		Poland
117	Polsko-Amerykanskie Kliniki Serca, Szpital Powiatowy	Mielec		Poland
118	Samodzielny Pobliszny Zaklad W Mielcu	Mielec		Poland
119	Myslowickie Centrum Zdrowia	Myslowice		Poland
120	Samodzielna Publiczna Stacja Pogotowia Ratunkowego, Samodzielna Publiczna Stacja Pogotowia Ratunkowego W Niepolomicach	Niepolomice		Poland
121	Intercard Nowy Sacz	Nowy Sacz		Poland
122	Nzoz Nowy Szpital W Olkuszu	Olkusz		Poland
123	Szpital Powiatowy	Opatow		Poland
124	Carint	Ostrowiec Swietokrzyski		Poland
125	Spzoz Parczew	Parczew		Poland
126	Samodzielny Szpital Wojewodski	Piotrkow Trybunalski		Poland
127	Spzoz W Radzyniu Podlaskim	Radzyn Podlaski		Poland
128	Szpital Powiatowy W Sedziszowie Malopolskim	Sedziszow Malopolski		Poland
129	Oddzial Chorob Wewnetrznych	Staszow		Poland
130	Oddzial Kardiologii Al.Lotnikow Polskich 18	Swidnik		Poland
131	Szpital Zakonu Bonifratrow Sw.	Todz		Poland
132	Zdravstveni Dom Celje	Celje		Slovenia
133	Splosna Bolnisnica Izola, Polje 40	Izola		Slovenia
134	Oe Zdravstveni Dom Jesenice	Jesenice		Slovenia
135	Splosna Bolnisnica Jesenic	Jesenice		Slovenia
136	Zdravstveni Dom Lenart, Maistrova 22	Lenart		Slovenia
137	Univerzitetni Klinicni Center Ljubljana	Ljubljana		Slovenia
138	Zdravstveni Dom Ljubljana	Ljubljana		Slovenia
139	Univerzitetni Klinicni Center Maribor	Maribor		Slovenia
140	Zdravstveni Dom Dr. Adolfa Drolca Maribor	Maribor		Slovenia
141	Splosna Bolnisnica Novo Mesto/ Community Hospital Novo Mesto, Smihelska Cesta 1	Novo Mesto		Slovenia
142	Zdravstveni Dom Ormoz	Ormoz		Slovenia
143	Splosna Bolnisnica Ptuj, Interni Odelek, Potrceva Cesta 23	Ptuj		Slovenia
144	Zdravstveni Dom Slovenska Bistrica	Slovenska Bistrica		Slovenia
145	Zdravstveni Dom Slovenske Konjice	Slovenske Konjice		Slovenia

Sponsors and Collaborators

• The Medicines Company

Investigators

• Study Chair: Gabriel Steg, Prof, Executive Committee
• Study Chair: Christian Hamm, BSc, MD, PhD, International Steering Committee

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: The Medicines Company
• ClinicalTrials.gov Identifier: NCT01087723
• Other Study ID Numbers: TMC-BIV-08-03
• First Posted: Mar 16, 2010
• Last Update Posted: Feb 12, 2016
• Last Verified: Jan 1, 2016

• Keywords provided by The Medicines Company: EUROMAX; STEMI; STE-ACS; UFH; bivalirudin; PCI; ambulance study; STE-MI participants
• Additional relevant MeSH terms: Acute Coronary Syndrome; Syndrome; Heparin; Bivalirudin

Study Results

Participant Flow

Arm/Group Title	Bivalirudin	Standard of Care: Heparins With Optional GPI
Arm/Group Description	Given immediately upon enrolment as an intravenous (IV) bolus of 0.75 milligrams/kilogram (mg/kg), followed immediately by an infusion of 1.75 mg/kg/hour (mg/kg/h). This infusion was to be run continuously until completion of percutaneous coronary intervention (PCI), at which time the infusion was reduced to 0.25 mg/kg/h for at least 4 hours. An optional PCI-dose infusion of 1.75 mg/kg/h was also permitted for up to 4 hours at the discretion of the operator.	Standard-of-care anti-thrombotic therapy as outlined in the European Society of Cardiology Dosing Guidelines for Management of ST segment elevation acute coronary syndrome (STE-ACS ), not including bivalirudin: unfractionated heparin (UFH) (100 international units/kg [IU/kg] without glycoprotein IIb/IIIa inhibitor [GPI] and 60 IU/kg with GPI). Any of the following approved GPIs were used either as a routine strategy or as a bail out: eptifibatide (two 180-micrograms/kilogram [μg/kg] IV boluses with a 10-minute [min] interval followed by an infusion of 2.0 μg/kg/min for 72-96 hours); tirofiban (25 μg/kg followed by an infusion of 0.15 μg/kg/min for 18-24 hours); or abciximab (bolus of 0.25 mg/kg followed by an infusion of 0.125 μg/kg/min for 12-24 hours [maximum dose of 10 μg/min]). For this study, the control consisted of treatment with UFH or low molecular weight heparin (LMWH) with or without GPI and is referred to as "heparins with optional GPI."
Period Title: Overall Study
STARTED	1089	1109
Received at Least 1 Dose of Study Drug	1099	1094
COMPLETED	1075	1089
NOT COMPLETED	14	20

Baseline Characteristics

Arm/Group Title	Bivalirudin	Standard of Care: Heparins With Optional GPI	Total
Arm/Group Description	Given immediately upon enrollment as an IV bolus of 0.75 mg/kg, followed immediately by an infusion of 1.75 mg/kg/h. This infusion was to be run continuously until completion of PCI, at which time the infusion was reduced to 0.25 mg/kg/h for at least 4 hours. An optional PCI-dose infusion of 1.75 mg/kg/h was also permitted for up to 4 hours at the discretion of the operator.	Standard-of-care anti-thrombotic therapy as outlined in the European Society of Cardiology Dosing Guidelines for Management of STE-ACS, not including bivalirudin: UFH (100 international IU/kg without GPI and 60 IU/kg with GPI). Any of the following approved GPIs were used either as a routine strategy or as a bail out: eptifibatide (two 180-μg/kg IV boluses with a 10-min interval followed by an infusion of 2.0 μg/kg/min for 72-96 hours); tirofiban (25 μg/kg followed by an infusion of 0.15 μg/kg/min for 18-24 hours); or abciximab (bolus of 0.25 mg/kg followed by an infusion of 0.125 μg/kg/min for 12-24 hours [maximum dose of 10 μg/min]). For this study, the control consisted of treatment with UFH or LMWH with or without GPI and is referred to as "heparins with optional GPI."	Total of all reporting groups
Overall Participants	1089	1109	2198
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.4 (12.8)	62.0 (13.1)	61.7 (13.0)
Sex: Female, Male (Count of Participants)
Female	275 25.3%	248 22.4%	523 23.8%
Male	814 74.7%	861 77.6%	1675 76.2%
Region of Enrollment (participants) [Number]
Austria	4 0.4%	5 0.5%	9 0.4%
Czech Republic	0 0%	1 0.1%	1 0%
Netherlands	377 34.6%	391 35.3%	768 34.9%
Denmark	78 7.2%	72 6.5%	150 6.8%
Poland	55 5.1%	56 5%	111 5.1%
Italy	31 2.8%	41 3.7%	72 3.3%
France	398 36.5%	397 35.8%	795 36.2%
Germany	139 12.8%	140 12.6%	279 12.7%
Slovenia	7 0.6%	6 0.5%	13 0.6%
Medical history: Participant Has Diabetes (participants) [Number]
Number [participants]	127 11.7%	169 15.2%	296 13.5%
Medical history: Participant Is a Current smoker (within past 30 days) (participants) [Number]
Number [participants]	453 41.6%	472 42.6%	925 42.1%
Medical history: Participant Has Hypertension (participants) [Number]
Number [participants]	459 42.1%	504 45.4%	963 43.8%
Medical history: Participant Has Hyperlipidemia (participants) [Number]
Number [participants]	398 36.5%	417 37.6%	815 37.1%
Medical history: Participant Has Had Previous myocardial infarction (MI) (participants) [Number]
Number [participants]	380 34.9%	113 10.2%	493 22.4%

Outcome Measures

1. Primary Outcome

Title	The Composite Incidence of Death and Non-coronary Artery Bypass Graft (CABG) Major Bleeding
Description	A participant was defined to have had a composite event if the participant experienced at least 1 of the 2 components (death or non-CABG major bleeding) of the composite. Incidence=the number of participants to experience the event/total number of at risk participants x 100. Death was defined as death from any cause at any time. Non-CABG major bleeding was defined as any 1 of the following: intra-cranial, retroperitoneal, intraocular, access site hemorrhage requiring radiological or surgical intervention, reduction in hemoglobin (Hb) concentration of >4 grams/deciliter (g/dL) without an overt source of bleeding, reduction in hemoglobin concentration of >3 g/dL with an overt source of bleeding; re-intervention for bleeding, or use of any blood product transfusion.
Time Frame	Within 30 days

Outcome Measure Data

Analysis Population Description

Participants who were randomized and signed an ICF; ITT population

Arm/Group Title	Bivalirudin	Standard of Care: Heparins With Optional GPI
Arm/Group Description	Given immediately upon enrollment as an IV bolus of 0.75 mg/kg, followed immediately by an infusion of 1.75 mg/kg/h. This infusion was to be run continuously until completion of PCI, at which time the infusion was reduced to 0.25 mg/kg/h for at least 4 hours. An optional PCI-dose infusion of 1.75 mg/kg/h was also permitted for up to 4 hours at the discretion of the operator.	Standard-of-care anti-thrombotic therapy as outlined in the European Society of Cardiology Dosing Guidelines for Management of STE-ACS, not including bivalirudin: UFH (100 international IU/kg without GPI and 60 IU/kg with GPI). Any of the following approved GPIs were used either as a routine strategy or as a bail out: eptifibatide (two 180-μg/kg IV boluses with a 10-min interval followed by an infusion of 2.0 μg/kg/min for 72-96 hours); tirofiban (25 μg/kg followed by an infusion of 0.15 μg/kg/min for 18-24 hours); or abciximab (bolus of 0.25 mg/kg followed by an infusion of 0.125 μg/kg/min for 12-24 hours [maximum dose of 10 μg/min]). For this study, the control consisted of treatment with UFH or LMWH with or without GPI and is referred to as "heparins with optional GPI."
Measure Participants	1089	1109
Number [percentage of participants]	5.1 0.5%	8.5 0.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bivalirudin, Standard of Care: Heparins With Optional GPI
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0014
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Relative risk
	Estimated Value	0.60
	Confidence Interval	(2-Sided) 95%; 0.43 to 0.82
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	The Composite Incidence of Death, Re-infarction (MI), or Non-CABG Major Bleeding
Description	A participant had a composite event if the participant experienced at least 1 of the 3 components (death, re-infarction [MI], or non-CABG major bleeding) of the composite. Incidence=the number of participants to experience the event/total number of at risk participants x 100. Death was defined as death from any cause at any time. Non-CABG major bleeding was defined as any one of the following: intracranial, retroperitoneal, intraocular, access site hemorrhage requiring radiological or surgical intervention, reduction in Hb concentration of >4 g/dL without an overt source of bleeding, reduction in hemoglobin concentration of >3 g/dL with an overt source of bleeding, re-intervention for bleeding, use of any blood product transfusion. MI was defined as a positive diagnosis of re-infarction (new event) not associated with index PCI.
Time Frame	Within 30 days

Outcome Measure Data

Analysis Population Description

Participants who were randomized and signed an ICF; ITT population

Arm/Group Title	Bivalirudin	Standard of Care: Heparins With Optional GPI
Arm/Group Description	Given immediately upon enrollment as an IV bolus of 0.75 mg/kg, followed immediately by an infusion of 1.75 mg/kg/h. This infusion was to be run continuously until completion of PCI, at which time the infusion was reduced to 0.25 mg/kg/h for at least 4 hours. An optional PCI-dose infusion of 1.75 mg/kg/h was also permitted for up to 4 hours at the discretion of the operator.	Standard-of-care anti-thrombotic therapy as outlined in the European Society of Cardiology Dosing Guidelines for Management of STE-ACS, not including bivalirudin: UFH (100 international IU/kg without GPI and 60 IU/kg with GPI). Any of the following approved GPIs were used either as a routine strategy or as a bail out: eptifibatide (two 180-μg/kg IV boluses with a 10-min interval followed by an infusion of 2.0 μg/kg/min for 72-96 hours); tirofiban (25 μg/kg followed by an infusion of 0.15 μg/kg/min for 18-24 hours); or abciximab (bolus of 0.25 mg/kg followed by an infusion of 0.125 μg/kg/min for 12-24 hours [maximum dose of 10 μg/min]). For this study, the control consisted of treatment with UFH or LMWH with or without GPI and is referred to as "heparins with optional GPI."
Measure Participants	1089	1109
Number [percentage of participants]	6.6 0.6%	9.2 0.8%

3. Secondary Outcome

Title	The Incidence of Death, Re-infarction, Non-CABG-related Major Bleeding, or Ischemia-driven Revascularization (IDR)
Description	Incidence=number of participants to experience the event/total number of at risk participants x 100. Death from any cause at any time. Re-infarction was a positive diagnosis of re-infarction not associated with index PCI. Non-CABG major bleeding was any 1 of: intracranial, retroperitoneal, intraocular, access site hemorrhage requiring radiological or surgical intervention, reduction in Hb concentration of >4 g/dL without an overt source of bleeding, reduction in hemoglobin concentration of >3 g/dL with an overt source of bleeding, re-intervention for bleeding, use of any blood product transfusion. IDR was any refractory ischemia-driven repeat percutaneous intervention or bypass graft surgery involving any native coronary or pre-existing bypass graft vessel. In the absence of pain, new ST segment changes indicative of ischemia, acute pulmonary edema, ventricular arrhythmias, or hemodynamic instability presumed to be ischemic in origin, will constitute sufficient evidence of ischemia.
Time Frame	Within 30 days

Outcome Measure Data

Analysis Population Description

Participants who were randomized and signed an ICF; ITT population

Arm/Group Title	Bivalirudin	Standard of Care: Heparins With Optional GPI
Arm/Group Description	Given immediately upon enrollment as an IV bolus of 0.75 mg/kg, followed immediately by an infusion of 1.75 mg/kg/h. This infusion was to be run continuously until completion of PCI, at which time the infusion was reduced to 0.25 mg/kg/h for at least 4 hours. An optional PCI-dose infusion of 1.75 mg/kg/h was also permitted for up to 4 hours at the discretion of the operator.	Standard-of-care anti-thrombotic therapy as outlined in the European Society of Cardiology Dosing Guidelines for Management of STE-ACS, not including bivalirudin: UFH (100 international IU/kg without GPI and 60 IU/kg with GPI). Any of the following approved GPIs were used either as a routine strategy or as a bail out: eptifibatide (two 180-μg/kg IV boluses with a 10-min interval followed by an infusion of 2.0 μg/kg/min for 72-96 hours); tirofiban (25 μg/kg followed by an infusion of 0.15 μg/kg/min for 18-24 hours); or abciximab (bolus of 0.25 mg/kg followed by an infusion of 0.125 μg/kg/min for 12-24 hours [maximum dose of 10 μg/min]). For this study, the control consisted of treatment with UFH or LMWH with or without GPI and is referred to as "heparins with optional GPI."
Measure Participants	1089	1109
Death	2.9 0.3%	3.1 0.3%
Re-infarction	1.7 0.2%	0.9 0.1%
Non-CABG-related major bleeding	2.6 0.2%	6.0 0.5%
IDR	2.2 0.2%	1.5 0.1%

4. Secondary Outcome

Title	The Incidence of Death at 1 Year
Description	Incidence=the number of participants to experience the event/total number of at risk participants x 100. Death was defined as death from any cause at any time.
Time Frame	Within 1 Year

Outcome Measure Data

Analysis Population Description

Participants who were randomized and signed an ICF; ITT population

Arm/Group Title	Bivalirudin	Standard of Care: Heparins With Optional GPI
Arm/Group Description	Given immediately upon enrollment as an IV bolus of 0.75 mg/kg, followed immediately by an infusion of 1.75 mg/kg/h. This infusion was to be run continuously until completion of PCI, at which time the infusion was reduced to 0.25 mg/kg/h for at least 4 hours. An optional PCI-dose infusion of 1.75 mg/kg/h was also permitted for up to 4 hours at the discretion of the operator.	Standard-of-care anti-thrombotic therapy as outlined in the European Society of Cardiology Dosing Guidelines for Management of STE-ACS, not including bivalirudin: UFH (100 international IU/kg without GPI and 60 IU/kg with GPI). Any of the following approved GPIs were used either as a routine strategy or as a bail out: eptifibatide (two 180-μg/kg IV boluses with a 10-min interval followed by an infusion of 2.0 μg/kg/min for 72-96 hours); tirofiban (25 μg/kg followed by an infusion of 0.15 μg/kg/min for 18-24 hours); or abciximab (bolus of 0.25 mg/kg followed by an infusion of 0.125 μg/kg/min for 12-24 hours [maximum dose of 10 μg/min]). For this study, the control consisted of treatment with UFH or LMWH with or without GPI and is referred to as "heparins with optional GPI."
Measure Participants	1089	1109
Number [percentage of participants]	5.4 0.5%	5.3 0.5%

5. Secondary Outcome

Title	The Incidence of Major Bleeding: Thrombolysis in MI (TIMI) and Global Utilization of Streptokinase and tPA for Occluded Coronary Arteries (GUSTO)
Description	Incidence=the number of participants to experience the event/total number of at risk participants x 100. Major bleeding based on TIMI criteria was defined as any intra-cranial bleeding, or any bleeding associated with clinically overt signs associated with a drop in Hb of >5 g/dL (or, when Hb was not available, an absolute drop in hematocrit [Hct] >15%). Major bleeding based on GUSTO criteria was defined as severe/life-threatening: intra-cranial hemorrhage or resulting in substantial hemodynamic compromise requiring treatment.
Time Frame	Within 30 days

Outcome Measure Data

Analysis Population Description

Participants who were randomized and signed an ICF; ITT population

Arm/Group Title	Bivalirudin	Standard of Care: Heparins With Optional GPI
Arm/Group Description	Given immediately upon enrollment as an IV bolus of 0.75 mg/kg, followed immediately by an infusion of 1.75 mg/kg/h. This infusion was to be run continuously until completion of PCI, at which time the infusion was reduced to 0.25 mg/kg/h for at least 4 hours. An optional PCI-dose infusion of 1.75 mg/kg/h was also permitted for up to 4 hours at the discretion of the operator.	Standard-of-care anti-thrombotic therapy as outlined in the European Society of Cardiology Dosing Guidelines for Management of STE-ACS, not including bivalirudin: UFH (100 international IU/kg without GPI and 60 IU/kg with GPI). Any of the following approved GPIs were used either as a routine strategy or as a bail out: eptifibatide (two 180-μg/kg IV boluses with a 10-min interval followed by an infusion of 2.0 μg/kg/min for 72-96 hours); tirofiban (25 μg/kg followed by an infusion of 0.15 μg/kg/min for 18-24 hours); or abciximab (bolus of 0.25 mg/kg followed by an infusion of 0.125 μg/kg/min for 12-24 hours [maximum dose of 10 μg/min]). For this study, the control consisted of treatment with UFH or LMWH with or without GPI and is referred to as "heparins with optional GPI."
Measure Participants	1089	1109
Major bleeding: TIMI	1.3 0.1%	2.1 0.2%
Major bleeding: GUSTO	1.3 0.1%	2.3 0.2%

6. Secondary Outcome

Title	The Incidence of Minor Bleeding: TIMI and GUSTO
Description	Incidence=the number of participants to experience the event/total number of at risk participants x 100. Minor bleeding based on TIMI criteria was defined as any clinically overt sign of bleeding (including observation by imaging techniques) that was associated with a fall in Hb of ≥3 g/dL and ≤5 g/dL (or, when Hb was not available, an absolute drop in Hct of ≥9% and ≤15%). Minor bleeding based on GUSTO criteria was defined as other bleed not requiring blood transfusion or causing hemodynamic compromise.
Time Frame	Within 30 days

Outcome Measure Data

Analysis Population Description

Participants who were randomized and signed an ICF; ITT population

Arm/Group Title	Bivalirudin	Standard of Care: Heparins With Optional GPI
Arm/Group Description	Given immediately upon enrollment as an IV bolus of 0.75 mg/kg, followed immediately by an infusion of 1.75 mg/kg/h. This infusion was to be run continuously until completion of PCI, at which time the infusion was reduced to 0.25 mg/kg/h for at least 4 hours. An optional PCI-dose infusion of 1.75 mg/kg/h was also permitted for up to 4 hours at the discretion of the operator.	Standard-of-care anti-thrombotic therapy as outlined in the European Society of Cardiology Dosing Guidelines for Management of STE-ACS, not including bivalirudin: UFH (100 international IU/kg without GPI and 60 IU/kg with GPI). Any of the following approved GPIs were used either as a routine strategy or as a bail out: eptifibatide (two 180-μg/kg IV boluses with a 10-min interval followed by an infusion of 2.0 μg/kg/min for 72-96 hours); tirofiban (25 μg/kg followed by an infusion of 0.15 μg/kg/min for 18-24 hours); or abciximab (bolus of 0.25 mg/kg followed by an infusion of 0.125 μg/kg/min for 12-24 hours [maximum dose of 10 μg/min]). For this study, the control consisted of treatment with UFH or LMWH with or without GPI and is referred to as "heparins with optional GPI."
Measure Participants	1089	1109
Minor bleeding: TIMI	6.5 0.6%	11.2 1%
Minor bleeding: GUSTO	6.5 0.6%	11.0 1%

7. Secondary Outcome

Title	The Incidence of Stent Thrombosis (Academic Research Consortium [ARC Definition])
Description	Incidence=the number of participants to experience the event/total number of at risk participants x 100. Stent thrombosis, based on the ARC definition, was defined as angiographic confirmation of stent thrombosis, non-occlusive thrombus, occlusive thrombus, or pathological confirmation of stent thrombosis.
Time Frame	Within 30 days

Outcome Measure Data

Analysis Population Description

Participants who were randomized and signed an ICF; ITT population

Arm/Group Title	Bivalirudin	Standard of Care: Heparins With Optional GPI
Arm/Group Description	Given immediately upon enrollment as an IV bolus of 0.75 mg/kg, followed immediately by an infusion of 1.75 mg/kg/h. This infusion was to be run continuously until completion of PCI, at which time the infusion was reduced to 0.25 mg/kg/h for at least 4 hours. An optional PCI-dose infusion of 1.75 mg/kg/h was also permitted for up to 4 hours at the discretion of the operator.	Standard-of-care anti-thrombotic therapy as outlined in the European Society of Cardiology Dosing Guidelines for Management of STE-ACS, not including bivalirudin: UFH (100 international IU/kg without GPI and 60 IU/kg with GPI). Any of the following approved GPIs were used either as a routine strategy or as a bail out: eptifibatide (two 180-μg/kg IV boluses with a 10-min interval followed by an infusion of 2.0 μg/kg/min for 72-96 hours); tirofiban (25 μg/kg followed by an infusion of 0.15 μg/kg/min for 18-24 hours); or abciximab (bolus of 0.25 mg/kg followed by an infusion of 0.125 μg/kg/min for 12-24 hours [maximum dose of 10 μg/min]). For this study, the control consisted of treatment with UFH or LMWH with or without GPI and is referred to as "heparins with optional GPI."
Measure Participants	1089	1109
Number [percentage of participants]	1.6 0.1%	0.5 0%

8. Secondary Outcome

Title	The Incidence of Thrombocytopenia
Description	Incidence=the number of participants to experience the event/total number of at risk participants x 100. Thrombocytopenia was defined as a post-procedural platelet count <100,000 cells/millimeter cubed (cells/mm^3) in a participant with a baseline or pre-procedural platelet count >100,000 cells/mm^3.
Time Frame	Within 30 days

Outcome Measure Data

Analysis Population Description

Participants who were randomized and signed an ICF; ITT population

Arm/Group Title	Bivalirudin	Standard of Care: Heparins With Optional GPI
Arm/Group Description	Given immediately upon enrollment as an IV bolus of 0.75 mg/kg, followed immediately by an infusion of 1.75 mg/kg/h. This infusion was to be run continuously until completion of PCI, at which time the infusion was reduced to 0.25 mg/kg/h for at least 4 hours. An optional PCI-dose infusion of 1.75 mg/kg/h was also permitted for up to 4 hours at the discretion of the operator.	Standard-of-care anti-thrombotic therapy as outlined in the European Society of Cardiology Dosing Guidelines for Management of STE-ACS, not including bivalirudin: UFH (100 international IU/kg without GPI and 60 IU/kg with GPI). Any of the following approved GPIs were used either as a routine strategy or as a bail out: eptifibatide (two 180-μg/kg IV boluses with a 10-min interval followed by an infusion of 2.0 μg/kg/min for 72-96 hours); tirofiban (25 μg/kg followed by an infusion of 0.15 μg/kg/min for 18-24 hours); or abciximab (bolus of 0.25 mg/kg followed by an infusion of 0.125 μg/kg/min for 12-24 hours [maximum dose of 10 μg/min]). For this study, the control consisted of treatment with UFH or LMWH with or without GPI and is referred to as "heparins with optional GPI."
Measure Participants	1089	1109
Number [percentage of participants]	0.7 0.1%	1.4 0.1%

9. Secondary Outcome

Title	The Incidence of Stroke
Description	Incidence=the number of participants to experience the event/total number of at risk participants x 100. Stroke was defined as a sudden, focal neurological defect resulting from a cerebrovascular cause, resulting in death or lasting greater than 24 hours that was not due to a readily identifiable cause, such as a tumor, infection, or trauma.
Time Frame	Within 30 days

Outcome Measure Data

Analysis Population Description

Participants who were randomized and signed an ICF; ITT population

Arm/Group Title	Bivalirudin	Standard of Care: Heparins With Optional GPI
Arm/Group Description	Given immediately upon enrollment as an IV bolus of 0.75 mg/kg, followed immediately by an infusion of 1.75 mg/kg/h. This infusion was to be run continuously until completion of PCI, at which time the infusion was reduced to 0.25 mg/kg/h for at least 4 hours. An optional PCI-dose infusion of 1.75 mg/kg/h was also permitted for up to 4 hours at the discretion of the operator.	Standard-of-care anti-thrombotic therapy as outlined in the European Society of Cardiology Dosing Guidelines for Management of STE-ACS, not including bivalirudin: UFH (100 international IU/kg without GPI and 60 IU/kg with GPI). Any of the following approved GPIs were used either as a routine strategy or as a bail out: eptifibatide (two 180-μg/kg IV boluses with a 10-min interval followed by an infusion of 2.0 μg/kg/min for 72-96 hours); tirofiban (25 μg/kg followed by an infusion of 0.15 μg/kg/min for 18-24 hours); or abciximab (bolus of 0.25 mg/kg followed by an infusion of 0.125 μg/kg/min for 12-24 hours [maximum dose of 10 μg/min]). For this study, the control consisted of treatment with UFH or LMWH with or without GPI and is referred to as "heparins with optional GPI."
Measure Participants	1089	1109
Number [percentage of participants]	0.6 0.1%	1.0 0.1%

Adverse Events

Time Frame	From screening to Day 30
Arm/Group Title	Bivalirudin		Standard of Care: Heparins With Optional GPI
Arm/Group Description	Given immediately upon enrollment as an IV bolus of 0.75 mg/kg, followed immediately by an infusion of 1.75 mg/kg/h. This infusion was to be run continuously until completion of PCI, at which time the infusion was reduced to 0.25 mg/kg/h for at least 4 hours. An optional PCI-dose infusion of 1.75 mg/kg/h was also permitted for up to 4 hours at the discretion of the operator.		Standard-of-care anti-thrombotic therapy as outlined in the European Society of Cardiology Dosing Guidelines for Management of STE-ACS, not including bivalirudin: UFH (100 international IU/kg without GPI and 60 IU/kg with GPI). Any of the following approved GPIs were used either as a routine strategy or as a bail out: eptifibatide (two 180-μg/kg IV boluses with a 10-min interval followed by an infusion of 2.0 μg/kg/min for 72-96 hours); tirofiban (25 μg/kg followed by an infusion of 0.15 μg/kg/min for 18-24 hours); or abciximab (bolus of 0.25 mg/kg followed by an infusion of 0.125 μg/kg/min for 12-24 hours [maximum dose of 10 μg/min]). For this study, the control consisted of treatment with UFH or LMWH with or without GPI and is referred to as "heparins with optional GPI."
All Cause Mortality
	Bivalirudin		Standard of Care: Heparins With Optional GPI
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Bivalirudin		Standard of Care: Heparins With Optional GPI
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	145/1099 (13.2%)		129/1094 (11.8%)
Cardiac disorders
Ventricular fibrillation	39/1099 (3.5%)		28/1094 (2.6%)
Cardiogenic shock	21/1099 (1.9%)		17/1094 (1.6%)
Cardiac arrest	7/1099 (0.6%)		17/1094 (1.6%)
Cardiac failure	8/1099 (0.7%)		10/1094 (0.9%)
Coronary artery dissection	7/1099 (0.6%)		2/1094 (0.2%)
Ventricular tachycardia	3/1099 (0.3%)		4/1094 (0.4%)
Bradycardia	2/1099 (0.2%)		3/1094 (0.3%)
Atrioventricular block complete	3/1099 (0.3%)		2/1094 (0.2%)
Angina pectoris	2/1099 (0.2%)		3/1094 (0.3%)
Intracardiac thrombus	3/1099 (0.3%)		1/1094 (0.1%)
Atrial fibrillation	2/1099 (0.2%)		2/1094 (0.2%)
Coronary artery perforation	2/1099 (0.2%)		1/1094 (0.1%)
Ventricular septal defect acquired	2/1099 (0.2%)		0/1094 (0%)
Tachycardia	0/1099 (0%)		2/1094 (0.2%)
Coronary no-reflow phenomenon	1/1099 (0.1%)		1/1094 (0.1%)
Coronary artery stenosis	0/1099 (0%)		2/1094 (0.2%)
Cardio-respiratory arrest	2/1099 (0.2%)		0/1094 (0%)
Atrioventricular block	2/1099 (0.2%)		0/1094 (0%)
Acute myocardial infarction	0/1099 (0%)		2/1094 (0.2%)
Ventricular extrasystoles	1/1099 (0.1%)		0/1094 (0%)
Ventricular arrhythmia	0/1099 (0%)		1/1094 (0.1%)
Ventricle rupture	1/1099 (0.1%)		0/1094 (0%)
Stress cardiomyopathy	1/1099 (0.1%)		0/1094 (0%)
Sinus arrest	1/1099 (0.1%)		0/1094 (0%)
Sick sinus syndrome	1/1099 (0.1%)		0/1094 (0%)
Pulseless electrical activity	0/1099 (0%)		1/1094 (0.1%)
Pericarditis	1/1099 (0.1%)		0/1094 (0%)
Pericardial effusion	1/1099 (0.1%)		0/1094 (0%)
Papillary muscle rupture	0/1099 (0%)		1/1094 (0.1%)
Palpitations	1/1099 (0.1%)		0/1094 (0%)
Myocardial infarction	0/1099 (0%)		1/1094 (0.1%)
Mitral valve incompetence	1/1099 (0.1%)		0/1094 (0%)
Interventricular septum rupture	0/1099 (0%)		1/1094 (0.1%)
Cardiac tamponade	1/1099 (0.1%)		0/1094 (0%)
Cardiac failure acute	0/1099 (0%)		1/1094 (0.1%)
Cardiac disorder	1/1099 (0.1%)		0/1094 (0%)
Cardiac asthma	1/1099 (0.1%)		0/1094 (0%)
Atrioventricular block second degree	1/1099 (0.1%)		0/1094 (0%)
Angina unstable	0/1099 (0%)		1/1094 (0.1%)
Congenital, familial and genetic disorders
Ventricular septal defect	1/1099 (0.1%)		0/1094 (0%)
Gastrointestinal disorders
Intestinal infarction	1/1099 (0.1%)		1/1094 (0.1%)
Ileus	0/1099 (0%)		1/1094 (0.1%)
Abdominal wall haemorrhage	1/1099 (0.1%)		0/1094 (0%)
Abdominal pain upper	0/1099 (0%)		1/1094 (0.1%)
General disorders
Chest pain	5/1099 (0.5%)		3/1094 (0.3%)
Multi-organ failure	3/1099 (0.3%)		0/1094 (0%)
Non-cardiac chest pain	1/1099 (0.1%)		1/1094 (0.1%)
Death	1/1099 (0.1%)		1/1094 (0.1%)
Sudden cardiac death	1/1099 (0.1%)		0/1094 (0%)
Malaise	1/1099 (0.1%)		0/1094 (0%)
Chest discomfort	1/1099 (0.1%)		0/1094 (0%)
Cardiac death	0/1099 (0%)		1/1094 (0.1%)
Hepatobiliary disorders
Cholelithiasis	1/1099 (0.1%)		0/1094 (0%)
Infections and infestations
Pneumonia	2/1099 (0.2%)		5/1094 (0.5%)
Septic shock	3/1099 (0.3%)		0/1094 (0%)
Urinary tract infection	1/1099 (0.1%)		1/1094 (0.1%)
Sepsis	0/1099 (0%)		1/1094 (0.1%)
Pneumonia staphylococcal	1/1099 (0.1%)		0/1094 (0%)
Pneumonia haemophilus	1/1099 (0.1%)		0/1094 (0%)
Clostridial infection	0/1099 (0%)		1/1094 (0.1%)
Bronchitis	0/1099 (0%)		1/1094 (0.1%)
Appendicitis	0/1099 (0%)		1/1094 (0.1%)
Injury, poisoning and procedural complications
Gastrointestinal injury	1/1099 (0.1%)		0/1094 (0%)
Facial bones fracture	0/1099 (0%)		1/1094 (0.1%)
Investigations
Arteriogram coronary	1/1099 (0.1%)		0/1094 (0%)
Musculoskeletal and connective tissue disorders
Compartment syndrome	1/1099 (0.1%)		0/1094 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Plasmacytoma	1/1099 (0.1%)		0/1094 (0%)
Pancreatic neoplasm	1/1099 (0.1%)		0/1094 (0%)
Abdominal neoplasm	0/1099 (0%)		1/1094 (0.1%)
Nervous system disorders
Syncope	2/1099 (0.2%)		0/1094 (0%)
Presyncope	1/1099 (0.1%)		0/1094 (0%)
Ischaemic stroke	1/1099 (0.1%)		0/1094 (0%)
Hypotonia	1/1099 (0.1%)		0/1094 (0%)
Dizziness	0/1099 (0%)		1/1094 (0.1%)
Cerebral infarction	0/1099 (0%)		1/1094 (0.1%)
Psychiatric disorders
Hallucination	0/1099 (0%)		1/1094 (0.1%)
Renal and urinary disorders
Renal failure acute	4/1099 (0.4%)		4/1094 (0.4%)
Renal failure	1/1099 (0.1%)		0/1094 (0%)
Nephropathy toxic	0/1099 (0%)		1/1094 (0.1%)
Calculus urinary	0/1099 (0%)		1/1094 (0.1%)
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema	3/1099 (0.3%)		5/1094 (0.5%)
Pulmonary oedema	2/1099 (0.2%)		1/1094 (0.1%)
Dyspnoea	2/1099 (0.2%)		1/1094 (0.1%)
Pleural effusion	1/1099 (0.1%)		1/1094 (0.1%)
Lung disorder	0/1099 (0%)		2/1094 (0.2%)
Chronic obstructive pulmonary disease	1/1099 (0.1%)		1/1094 (0.1%)
Respiratory failure	0/1099 (0%)		1/1094 (0.1%)
Orthopnoea	0/1099 (0%)		1/1094 (0.1%)
Laryngeal oedema	1/1099 (0.1%)		0/1094 (0%)
Dyspnoea exertional	0/1099 (0%)		1/1094 (0.1%)
Vascular disorders
Aortic dissection	4/1099 (0.4%)		0/1094 (0%)
Hypotension	0/1099 (0%)		2/1094 (0.2%)
Aortic stenosis	1/1099 (0.1%)		1/1094 (0.1%)
Aortic aneurysm rupture	2/1099 (0.2%)		0/1094 (0%)
Reperfusion injury	1/1099 (0.1%)		0/1094 (0%)
Hypertensive crisis	0/1099 (0%)		1/1094 (0.1%)
Haemodynamic instability	1/1099 (0.1%)		0/1094 (0%)
Circulatory collapse	1/1099 (0.1%)		0/1094 (0%)
Other (Not Including Serious) Adverse Events
	Bivalirudin		Standard of Care: Heparins With Optional GPI
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	134/1099 (12.2%)		119/1094 (10.9%)
Cardiac disorders
Ventricular tachycardia	57/1099 (5.2%)		39/1094 (3.6%)
Atrial fibrillation	35/1099 (3.2%)		35/1094 (3.2%)
Bradycardia	20/1099 (1.8%)		25/1094 (2.3%)
Vascular disorders
Hypotension	22/1099 (2%)		20/1094 (1.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.