European Ambulance Acute Coronary Syndrome (ACS) Angiography Trial

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.

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:

• 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

Exclusion criteria

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