European Ambulance Acute Coronary Syndrome (ACS) Angiography Trial

Acute Coronary Syndrome Clinical Trial

— EUROMAX  

Official title:

Multi-centre, Multi-national, Prospective, Randomised, Open-label, Comparison of Bivalirudin to Other Guideline Based Current Therapies (Excluding Bivalirudin)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01087723
• Other study ID #: TMC-BIV-08-03
• Status: Completed
• Phase: Phase 3
• First received: March 12, 2010
• Last updated: January 13, 2016
• Start date: March 2010
• Est. completion date: August 2014

Study information

• Verified date: January 2016
• Source: The Medicines Company
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Federal Office for Safety in Health Care
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2198
• Est. completion date: August 2014
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

4. 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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Coronary Syndrome

Intervention

Drug:
• Bivalirudin

• Heparin

Locations

Country	Name	City	State
Austria	Hanusch Krankenhaus	Wien
Austria	Magistratsabeilung 70, Wiener	Wien
Austria	Universitats-Klinik Fur	Wien
Austria	Wilhelminenspital MA 6 - BA 19	Wien
Czech Republic	Zdravotnicka Zachranna Sluzba	Ceske Budejovice
Denmark	Aarhus Universitetshospital	Aarhus
Denmark	Akutlaegebil Kobenhavn, Hc Andersens Boulevard 23	Copenhagen
Denmark	Rigshospitalet	Copenhagen
Denmark	Gentofte Hospital	Hellerup
Denmark	Akutlaegebil Nordsjaelland	Hillerod
Denmark	Laegeambulancen Odense	Odense
Denmark	Odense Universitets Hospital	Odense
France	Hopital Europeen Paris La Roseraie	Aubervilliers
France	Hospital Avicenne, Pharmacie -Gestion Des Essais Cliniques	Bobigny
France	Chu De Bordeaux - Hopital Pellegrin	Bordeaux Cedex
France	Centre Hospitalier Bourg En Bresse	Bourg En Bresse
France	Clinique Convert	Bourg En Bresse
France	Ch Jacques Coeur	Bourges
France	Centre Hospitalier Universitaire De Caen	Caen
France	Hopital Prive Saint Martin	Caen
France	Service De Cardiologie	Cedex
France	Ch Chateauroux	Chateauroux
France	Chu Clermont-Ferrand, Hopital	Clermont Ferrand
France	Samu-Smur Chu Clermont-Ferrand	Clermont Ferrand
France	Hopital Beaujon	Clichy
France	Ch Sud Francilien - Site Corbeil	Corbeil Essonne
France	Ch Sud Francilien - Site Corbeil, Pharmacie	Corbeil-Essonnes Cedex
France	Capio - Clinique Des Cedres	Cornebarrieu
France	Hospital Henri Mondor, Pharmacie	Creteil
France	Samu 92 Hauts De Seine	Garches
France	Clinique Les Eaux Claires Ghm	Grenoble
France	Chu A Michallon Grenoble	La Tronche
France	Samu Chu A Michallon Grenoble	La Tronche
France	Hopital Andre Mignot - Centre Hospitalier De Versailles	Le Chesnay Cedex
France	Chr Lille	Lille
France	Samu 59/Samu Du Nord	Lille
France	Centre Hospitalier De Longjumeau	Longjumeau
France	Centre Hospitalier St Joseph St Luc	Lyon
France	Institut Hospitalier Jacques Cartier	Massy
France	Centre Hospitalier De Montelimar	Montelimar
France	Chi Le Raincy - Montfermeil Site De Montfermeil	Montfermeil
France	Clinique Ambroise Pare	Neuilly
France	Centre Hospitalier	Paris
France	Hopital Bichat Claude Bernard	Paris
France	Hopital Europeen Georges Pompidou	Paris
France	Ch De Pau Hopital Francois Mitterand	Pau
France	Samu Ch De Pau	Pau
France	Cardiologic Hospital - Coronary Care Unit, University of Bordeaux	Pessac
France	Pole Smur, Samu 77 - Medecine	Seine et Marne
France	Clinique Belledonne	St Martin D Heres
France	Chu De Toulouse - Hopital Paule De Viguier	Toulouse
France	Chu Toulouse - Hopital Rangueil	Toulouse
France	Clinique Pasteur	Toulouse
France	Polyclinique Du Parc	Toulouse
France	Centre Hospitalier De Valence	Valence
France	Centre Hospitalier De Vienne Centre Hospitalier Lucien Hussel	Vienne
Germany	Kerckhoff Heart Center	Bad Nauheim
Germany	Rettungsdienst Wetteraukreis	Bad Nauheim
Germany	Charite Universitatsmedizin Berlin Campus Virchow-Klinikum	Berlin
Germany	Lutzowstrabe	Berlin
Germany	Sana Klinikum Lichtenberg Oskar Ziethen Krankenhaus, Fanningerstrasse 32	Berlin
Germany	Universitatsklinikum Benjamin Franklin, Hindenburgdamm 30	Berlin
Germany	Klinikum Links Der Weser	Bremen
Germany	Evangelisches Bethesda Johanniter	Duisburg
Germany	Feuerwehr Duisburg	Duisburg
Germany	Herzzentrum Duisburg, Klinik Fur Kardiologie And Angiologie	Duisburg
Germany	Klinikum Duisburg Ggmbh	Duisburg
Germany	Klinikum Der Johann Wolfgang Goethe Universitat	Frankfurt
Germany	Medizinische Hochschule Hannover, Carl Neuberg Str. 1	Hannover
Germany	Klinikum Ludwigshafen	Ludwigshafen
Germany	Stadtisches Klinikum Luneburg, Bogelstr. 1	Luneburg
Germany	Helios Klinik Der Universitat Witten Herdecke	Wuppertal
Italy	Ospedale Maggiore	Bologna
Italy	Ospedle Di Bentivoglio	Bologna
Italy	Policlinico S.Orsola Malpighi	Bologna
Italy	Ospedale Di Assisi	Perugia
Italy	Ospedale Di Castiglione Del Lago	Perugia
Italy	Ospedale Di Todi	Perugia
Italy	Ospedale S.Maria Misericordia	Perugia
Italy	Asur Marche- Zona 1 Pesaro	Pesaro
Italy	Azienda Ospedaliera San Salvatore	Pesaro
Italy	Emergency Rescue & Mobile Als Unit, Lanciarini Pub	Pesaro
Netherlands	Betreft Research Regional	Amersfoort
Netherlands	Meander Medisch Centrum	Amersfoort
Netherlands	Rav Noord En Oost Gelderland	Amersfoort
Netherlands	Pharmacy Department	Nieuwegein
Netherlands	Regional Ambulance Service Gelderland Midden	Nieuwegein
Netherlands	St Antonius Ziekenhuis	Nieuwegein
Netherlands	Service Gelderland-Zuid Klinisch Geneesmiddelonderzoek Klinsche Farmacie Afd Klinsche Farmacie	Nijmegan
Netherlands	Cwz Klinisch Geneesmiddelonderzoek Klinische	Nijmegen
Netherlands	Kgo Team Regional Ambulance	Nijmegen
Netherlands	Regional Ambulance Service	Nijmegen
Netherlands	Regional Ambulance Service Gelderland Zuid	Nijmegen
Netherlands	Regional Ambulance Service Gelderland-Zuid Distributiecentrum	Nijmegen
Netherlands	Umc St.Radboud Nijmegen	Nijmegen
Netherlands	Department Of Cardiology	Utrecht
Netherlands	Umc Utrecht	Utrecht
Netherlands	Isala Klinieken	Zwolle
Netherlands	Tav Trial Team, Isala Klinieken Ioc Weezenlanden Afd	Zwolle
Poland	Poradnia Kardiologiczna	Bedzin
Poland	Malopolskie Centrum Sercowo	Chrzanow
Poland	Szpital Powiatowy W Chrzanowie	Chrzanow
Poland	Oddzial Polskiej-Amerikanskiej Kliniki Serca	Dabrowa Gornicza
Poland	Szpital Powiatowy W Debicy	Debica
Poland	Specialist Hospital Gorlice	Gorlice
Poland	Szpital Powiatowy Im. Jana Pawla Ii W Kolbuszowej	Kolbuszowa
Poland	Jagiellonian University Medical College,	Krakow
Poland	Krakowskie Centrum	Krakow
Poland	Oddzial Kardiologii	Krakow
Poland	Samodzielny Publiczny Zaklad Opieki	Krakow
Poland	Szpital Specjalistyczny Im Szpitalny Oddzial Ratunkowy	Krakow
Poland	Spzoz Szpital Im. J.Dietla W Krynicy Zdroj	Krynica Zdroj
Poland	Spzoz Lask	Lask
Poland	Szpital Powiatowy W Limanowej	Limanowa
Poland	Szpital Bieganskiego	Lodz
Poland	Medical University Of Lublin	Lublin
Poland	Polsko-Amerykanskie Kliniki Serca, Szpital Powiatowy	Mielec
Poland	Samodzielny Pobliszny Zaklad W Mielcu	Mielec
Poland	Myslowickie Centrum Zdrowia	Myslowice
Poland	Samodzielna Publiczna Stacja Pogotowia Ratunkowego, Samodzielna Publiczna Stacja Pogotowia Ratunkowego W Niepolomicach	Niepolomice
Poland	Intercard Nowy Sacz	Nowy Sacz
Poland	Nzoz Nowy Szpital W Olkuszu	Olkusz
Poland	Szpital Powiatowy	Opatow
Poland	Carint	Ostrowiec Swietokrzyski
Poland	Spzoz Parczew	Parczew
Poland	Samodzielny Szpital Wojewodski	Piotrkow Trybunalski
Poland	Spzoz W Radzyniu Podlaskim	Radzyn Podlaski
Poland	Szpital Powiatowy W Sedziszowie Malopolskim	Sedziszow Malopolski
Poland	Oddzial Chorob Wewnetrznych	Staszow
Poland	Oddzial Kardiologii Al.Lotnikow Polskich 18	Swidnik
Poland	Szpital Zakonu Bonifratrow Sw.	Todz
Slovenia	Zdravstveni Dom Celje	Celje
Slovenia	Splosna Bolnisnica Izola, Polje 40	Izola
Slovenia	Oe Zdravstveni Dom Jesenice	Jesenice
Slovenia	Splosna Bolnisnica Jesenic	Jesenice
Slovenia	Zdravstveni Dom Lenart, Maistrova 22	Lenart
Slovenia	Univerzitetni Klinicni Center Ljubljana	Ljubljana
Slovenia	Zdravstveni Dom Ljubljana	Ljubljana
Slovenia	Univerzitetni Klinicni Center Maribor	Maribor
Slovenia	Zdravstveni Dom Dr. Adolfa Drolca Maribor	Maribor
Slovenia	Splosna Bolnisnica Novo Mesto/ Community Hospital Novo Mesto, Smihelska Cesta 1	Novo Mesto
Slovenia	Zdravstveni Dom Ormoz	Ormoz
Slovenia	Splosna Bolnisnica Ptuj, Interni Odelek, Potrceva Cesta 23	Ptuj
Slovenia	Zdravstveni Dom Slovenska Bistrica	Slovenska Bistrica
Slovenia	Zdravstveni Dom Slovenske Konjice	Slovenske Konjice

Sponsors (1)

Lead Sponsor	Collaborator
The Medicines Company

Countries where clinical trial is conducted

Austria,  Czech Republic,  Denmark,  France,  Germany,  Italy,  Netherlands,  Poland,  Slovenia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Composite Incidence of Death and Non-coronary Artery Bypass Graft (CABG) Major Bleeding	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.	Within 30 days	Yes
Secondary	The Composite Incidence of Death, Re-infarction (MI), or Non-CABG Major Bleeding	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.	Within 30 days	Yes
Secondary	The Incidence of Death, Re-infarction, Non-CABG-related Major Bleeding, or Ischemia-driven Revascularization (IDR)	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.	Within 30 days	Yes
Secondary	The Incidence of Death at 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.	Within 1 Year	Yes
Secondary	The Incidence of Major Bleeding: Thrombolysis in MI (TIMI) and Global Utilization of Streptokinase and tPA for Occluded Coronary Arteries (GUSTO)	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.	Within 30 days	Yes
Secondary	The Incidence of Minor Bleeding: TIMI and GUSTO	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.	Within 30 days	Yes
Secondary	The Incidence of Stent Thrombosis (Academic Research Consortium [ARC Definition])	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.	Within 30 days	Yes
Secondary	The Incidence of Thrombocytopenia	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.	Within 30 days	Yes
Secondary	The Incidence of Stroke	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.	Within 30 days	Yes