European Ambulance Acute Coronary Syndrome (ACS) Angiography Trial
- Registration Number
- NCT01087723
- Lead Sponsor
- 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 2198
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:
-
Provided written informed consent before initiation of any study related procedures. Participants randomized in the ambulance may initially have signed an abridged version.
-
Aged ≥18 years at the time of randomization.
-
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
-
All participants would proceed with emergent angiography and primary PCI if indicated <2 hours after first medical contact
Participants were excluded from the study if any of the following exclusion criteria applied prior to randomization:
- 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.
- Participants who had undergone recent surgery (including biopsy) within the last 2 weeks.
- Participants who were on warfarin (not applicable if International Normalized Ratio known to be <1.5).
- Participants who had received UFH, LMWH, or bivalirudin immediately before randomization.
- Thrombolytic therapy within the last 48 hours.
- 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.
- Contraindications to angiography, including but not limited to severe peripheral vascular disease.
- 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.
- If it is known, a creatinine clearance <30 milliliter/minute or dialysis dependent.
- Previous enrolment in this study.
- 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.
- 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.
- 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).
- Estimated body weight of >120 kg
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Bivalirudin 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. Standard of Care: Heparins with Optional GPI Heparin 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."
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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.
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.
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.
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.
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.
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.
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.
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.
Trial Locations
- Locations (145)
Magistratsabeilung 70, Wiener
🇦🇹Wien, Austria
Universitats-Klinik Fur
🇦🇹Wien, Austria
Odense Universitets Hospital
🇩🇰Odense, Denmark
Hospital Avicenne, Pharmacie -Gestion Des Essais Cliniques
🇫🇷Bobigny, France
Chu De Bordeaux - Hopital Pellegrin
🇫🇷Bordeaux Cedex, France
Ch Jacques Coeur
🇫🇷Bourges, France
Centre Hospitalier Bourg En Bresse
🇫🇷Bourg En Bresse, France
Clinique Convert
🇫🇷Bourg En Bresse, France
Centre Hospitalier Universitaire De Caen
🇫🇷Caen, France
Service De Cardiologie
🇫🇷Cedex, France
Hopital Prive Saint Martin
🇫🇷Caen, France
Ch Chateauroux
🇫🇷Chateauroux, France
Chu Clermont-Ferrand, Hopital
🇫🇷Clermont Ferrand, France
Ch Sud Francilien - Site Corbeil, Pharmacie
🇫🇷Corbeil-Essonnes Cedex, France
Samu-Smur Chu Clermont-Ferrand
🇫🇷Clermont Ferrand, France
Capio - Clinique Des Cedres
🇫🇷Cornebarrieu, France
Hospital Henri Mondor, Pharmacie
🇫🇷Creteil, France
Chu A Michallon Grenoble
🇫🇷La Tronche, France
Clinique Les Eaux Claires Ghm
🇫🇷Grenoble, 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
Institut Hospitalier Jacques Cartier
🇫🇷Massy, France
Centre Hospitalier St Joseph St Luc
🇫🇷Lyon, France
Centre Hospitalier De Montelimar
🇫🇷Montelimar, France
Chi Le Raincy - Montfermeil Site De Montfermeil
🇫🇷Montfermeil, France
Clinique Ambroise Pare
🇫🇷Neuilly, France
Samu Ch De Pau
🇫🇷Pau, France
Hopital Europeen Georges Pompidou
🇫🇷Paris, France
Ch De Pau Hopital Francois Mitterand
🇫🇷Pau, France
Cardiologic Hospital - Coronary Care Unit, University of Bordeaux
🇫🇷Pessac, France
Clinique Belledonne
🇫🇷St Martin D Heres, France
Pole Smur, Samu 77 - Medecine
🇫🇷Seine et Marne, France
Chu De Toulouse - Hopital Paule De Viguier
🇫🇷Toulouse, France
Chu Toulouse - Hopital Rangueil
🇫🇷Toulouse, France
Clinique Pasteur
🇫🇷Toulouse, France
Oe Zdravstveni Dom Jesenice
🇸🇮Jesenice, Slovenia
Oddzial Kardiologii
🇵🇱Krakow, Poland
Splosna Bolnisnica Izola, Polje 40
🇸🇮Izola, Slovenia
Wilhelminenspital MA 6 - BA 19
🇦🇹Wien, Austria
Zdravotnicka Zachranna Sluzba
🇨🇿Ceske Budejovice, Czech Republic
Oddzial Chorob Wewnetrznych
🇵🇱Staszow, Poland
Hanusch Krankenhaus
🇦🇹Wien, Austria
Regional Ambulance Service Gelderland Zuid
🇳🇱Nijmegen, Netherlands
Umc Utrecht
🇳🇱Utrecht, Netherlands
Specialist Hospital Gorlice
🇵🇱Gorlice, Poland
Szpital Powiatowy Im. Jana Pawla Ii W Kolbuszowej
🇵🇱Kolbuszowa, Poland
Regional Ambulance Service Gelderland-Zuid Distributiecentrum
🇳🇱Nijmegen, Netherlands
Isala Klinieken
🇳🇱Zwolle, Netherlands
Tav Trial Team, Isala Klinieken Ioc Weezenlanden Afd
🇳🇱Zwolle, Netherlands
Malopolskie Centrum Sercowo
🇵🇱Chrzanow, Poland
Krakowskie Centrum
🇵🇱Krakow, Poland
Spzoz W Radzyniu Podlaskim
🇵🇱Radzyn Podlaski, Poland
Hopital Beaujon
🇫🇷Clichy, France
Ch Sud Francilien - Site Corbeil
🇫🇷Corbeil Essonne, France
Centre Hospitalier
🇫🇷Paris, France
Hopital Bichat Claude Bernard
🇫🇷Paris, France
Polyclinique Du Parc
🇫🇷Toulouse, France
Klinikum Links Der Weser
🇩🇪Bremen, Germany
Feuerwehr Duisburg
🇩🇪Duisburg, Germany
Ospedle Di Bentivoglio
🇮🇹Bologna, Italy
Betreft Research Regional
🇳🇱Amersfoort, Netherlands
Poradnia Kardiologiczna
🇵🇱Bedzin, Poland
Szpital Zakonu Bonifratrow Sw.
🇵🇱Todz, Poland
Zdravstveni Dom Celje
🇸🇮Celje, Slovenia
Aarhus Universitetshospital
🇩🇰Aarhus, Denmark
Akutlaegebil Kobenhavn, Hc Andersens Boulevard 23
🇩🇰Copenhagen, Denmark
Gentofte Hospital
🇩🇰Hellerup, Denmark
Akutlaegebil Nordsjaelland
🇩🇰Hillerod, Denmark
Laegeambulancen Odense
🇩🇰Odense, Denmark
Rigshospitalet
🇩🇰Copenhagen, Denmark
Hopital Europeen Paris La Roseraie
🇫🇷Aubervilliers, France
Ospedale Di Todi
🇮🇹Perugia, Italy
Azienda Ospedaliera San Salvatore
🇮🇹Pesaro, Italy
Samu 92 Hauts De Seine
🇫🇷Garches, France
Evangelisches Bethesda Johanniter
🇩🇪Duisburg, Germany
Klinikum Ludwigshafen
🇩🇪Ludwigshafen, Germany
Rettungsdienst Wetteraukreis
🇩🇪Bad Nauheim, Germany
Pharmacy Department
🇳🇱Nieuwegein, Netherlands
Regional Ambulance Service Gelderland Midden
🇳🇱Nieuwegein, Netherlands
Charite Universitatsmedizin Berlin Campus Virchow-Klinikum
🇩🇪Berlin, Germany
Ospedale Di Assisi
🇮🇹Perugia, Italy
Ospedale Di Castiglione Del Lago
🇮🇹Perugia, Italy
Ospedale S.Maria Misericordia
🇮🇹Perugia, Italy
Asur Marche- Zona 1 Pesaro
🇮🇹Pesaro, Italy
Emergency Rescue & Mobile Als Unit, Lanciarini Pub
🇮🇹Pesaro, Italy
Centre Hospitalier De Vienne Centre Hospitalier Lucien Hussel
🇫🇷Vienne, France
Universitatsklinikum Benjamin Franklin, Hindenburgdamm 30
🇩🇪Berlin, Germany
Medizinische Hochschule Hannover, Carl Neuberg Str. 1
🇩🇪Hannover, Germany
Meander Medisch Centrum
🇳🇱Amersfoort, Netherlands
Rav Noord En Oost Gelderland
🇳🇱Amersfoort, Netherlands
St Antonius Ziekenhuis
🇳🇱Nieuwegein, Netherlands
Kgo Team Regional Ambulance
🇳🇱Nijmegen, Netherlands
Centre Hospitalier De Valence
🇫🇷Valence, France
Kerckhoff Heart Center
🇩🇪Bad Nauheim, Germany
Herzzentrum Duisburg, Klinik Fur Kardiologie And Angiologie
🇩🇪Duisburg, Germany
Klinikum Duisburg Ggmbh
🇩🇪Duisburg, Germany
Klinikum Der Johann Wolfgang Goethe Universitat
🇩🇪Frankfurt, Germany
Ospedale Maggiore
🇮🇹Bologna, Italy
Policlinico S.Orsola Malpighi
🇮🇹Bologna, Italy
Stadtisches Klinikum Luneburg, Bogelstr. 1
🇩🇪Luneburg, Germany
Helios Klinik Der Universitat Witten Herdecke
🇩🇪Wuppertal, Germany
Service Gelderland-Zuid Klinisch Geneesmiddelonderzoek Klinsche Farmacie Afd Klinsche Farmacie
🇳🇱Nijmegan, Netherlands
Cwz Klinisch Geneesmiddelonderzoek Klinische
🇳🇱Nijmegen, Netherlands
Regional Ambulance Service
🇳🇱Nijmegen, Netherlands
Umc St.Radboud Nijmegen
🇳🇱Nijmegen, Netherlands
Department Of Cardiology
🇳🇱Utrecht, Netherlands
Szpital Powiatowy W Chrzanowie
🇵🇱Chrzanow, Poland
Szpital Powiatowy W Debicy
🇵🇱Debica, Poland
Oddzial Polskiej-Amerikanskiej Kliniki Serca
🇵🇱Dabrowa Gornicza, Poland
Jagiellonian University Medical College,
🇵🇱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
Carint
🇵🇱Ostrowiec Swietokrzyski, Poland
Spzoz Parczew
🇵🇱Parczew, Poland
Oddzial Kardiologii Al.Lotnikow Polskich 18
🇵🇱Swidnik, Poland
Splosna Bolnisnica Jesenic
🇸🇮Jesenice, Slovenia
Zdravstveni Dom Lenart, Maistrova 22
🇸🇮Lenart, Slovenia
Zdravstveni Dom Ljubljana
🇸🇮Ljubljana, Slovenia
Szpital Powiatowy W Limanowej
🇵🇱Limanowa, Poland
Myslowickie Centrum Zdrowia
🇵🇱Myslowice, Poland
Szpital Powiatowy
🇵🇱Opatow, Poland
Univerzitetni Klinicni Center Maribor
🇸🇮Maribor, Slovenia
Szpital Bieganskiego
🇵🇱Lodz, Poland
Samodzielny Szpital Wojewodski
🇵🇱Piotrkow Trybunalski, Poland
Medical University Of Lublin
🇵🇱Lublin, Poland
Polsko-Amerykanskie Kliniki Serca, Szpital Powiatowy
🇵🇱Mielec, Poland
Samodzielny Pobliszny Zaklad W Mielcu
🇵🇱Mielec, 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 W Sedziszowie Malopolskim
🇵🇱Sedziszow Malopolski, Poland
Univerzitetni Klinicni Center Ljubljana
🇸🇮Ljubljana, 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
Lutzowstrabe
🇩🇪Berlin, Germany
Sana Klinikum Lichtenberg Oskar Ziethen Krankenhaus, Fanningerstrasse 32
🇩🇪Berlin, Germany