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

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

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.


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Study Type : Interventional  (Clinical Trial)
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 : March 2010
Actual Primary Completion Date : August 2013
Actual Study Completion Date : August 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Blood Thinners

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




Primary Outcome Measures :
  1. The Composite Incidence of Death and Non-coronary Artery Bypass Graft (CABG) Major Bleeding [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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]) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01087723


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Locations
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Austria
Hanusch Krankenhaus
Wien, Austria
Magistratsabeilung 70, Wiener
Wien, Austria
Universitats-Klinik Fur
Wien, Austria
Wilhelminenspital MA 6 - BA 19
Wien, Austria
Czech Republic
Zdravotnicka Zachranna Sluzba
Ceske Budejovice, Czech Republic
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, Denmark
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, France
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, Germany
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, Italy
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 Gelderland Zuid
Nijmegen, Netherlands
Regional Ambulance Service Gelderland-Zuid Distributiecentrum
Nijmegen, Netherlands
Regional Ambulance Service
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, Netherlands
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, Poland
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, Slovenia
Sponsors and Collaborators
The Medicines Company
Investigators
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Study Chair: Gabriel Steg, Prof Executive Committee
Study Chair: Christian Hamm, BSc, MD, PhD International Steering Committee

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: The Medicines Company
ClinicalTrials.gov Identifier: NCT01087723     History of Changes
Other Study ID Numbers: TMC-BIV-08-03
First Posted: March 16, 2010    Key Record Dates
Results First Posted: February 12, 2016
Last Update Posted: February 12, 2016
Last Verified: January 2016

Keywords provided by The Medicines Company:
EUROMAX
STEMI
STE-ACS
UFH
bivalirudin
PCI
ambulance study
STE-MI participants

Additional relevant MeSH terms:
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Syndrome
Acute Coronary Syndrome
Disease
Pathologic Processes
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Heparin
Calcium heparin
Bivalirudin
Hirudins
Anticoagulants
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors