E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients presenting with ST-segment elevation acute coronary syndrome (STE-ACS) planned for primary percutaneous coronary itervention (PCI) management strategy |
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E.1.1.1 | Medical condition in easily understood language |
Patients presenting with ST-segment elevation acute coronary syndrome (STE-ACS) planned for primary percutaneous coronary itervention (PCI) management strategy |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10051592 |
E.1.2 | Term | Acute coronary syndrome |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10041894 |
E.1.2 | Term | ST segment elevation |
E.1.2 | System Organ Class | 10022891 - Investigations |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To show that the early administration of bivalirudin improves 30 day outcomes when
compared to the current standard of care in patients 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 centres where PCI is not
performed. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
ST segment resolution sub-analysis |
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E.3 | Principal inclusion criteria |
1.Patients randomised in the ambulance may initially sign an abridged version.
2. Be aged ≥18 years at the time of randomisation.
3. Have a presumed diagnosis of a STE-ACS with onset of symptoms of >20 minutes and
<12 hours with one or more of the following:
• ST segment elevation of ≥1 mm in ≥2 contiguous leads
• Presumably new left bundle branch block
• An infero-lateral MI with ST segment depression of ≥1 mm in ≥2 of leads V1-3)
with a positive terminal T wave
4. All patients must be scheduled for angiography +/- PCI (if indicated) <2 hours after first medical contact |
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E.4 | Principal exclusion criteria |
1. Any bleeding diathesis or severe haematological disease or history of
intra-cerebral mass, aneurysm, arterio-venous malformation, haemorrhagic stroke, intra-cranial haemorrhage or gastrointestinal or genitourinary bleeding within the last 2-weeks.
2. Patients who have undergone recent surgery (including biopsy) within the last two weeks.
3. Patients on warfarin (not applicable if INR known to be <1.5).
4. Patients who have received UFH, LMWH or bivalirudin immediately before randomisation.
5. Thrombolytic therapy within the last 48 hours.
Absolute contraindications or allergy that cannot 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 is known pregnant or nursing mothers. Women of child-bearing age will be asked if
they are pregnant or think that they may be pregnant.
9. If it is known a creatinine clearance <30 mL/min or dialysis dependent.
10. Previous enrolment in this study.
11. Treatment with other investigational drugs or devices within the 30 days preceding
randomisation or planned use of other investigational drugs or devices in this trial.
12. Patients may not be enrolled if the duration of randomised investigational medicinal
product (IMP) anti-thrombin infusion is likely to be less than 30 minutes from the time of
onset to the commencement of angiography.
13. Patients may not be enrolled within a primary PCI capable hospital (unless at the time of randomisation the catheter laboratory is not
available and the patient requires transfer to
another primary PCI capable hospital).
14. Estimated body weight of >120 kg. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this trial at 30 days is:
• A composite of death or non-CABG-related protocol major bleeding
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Death or re-infarction (MI) at 30 days
• Death at 30 days and 365 days
• Re-infarction (MI) at 30 days
• IDR at 30 days
• Death, re-infarction (MI) or IDR at 30 days
• Death, re-infarction (MI) or non-CABG-related protocol major bleeding at 30 days
• Major bleeding at 30 days (protocol, TIMI and GUSTO)
• Minor bleeding at 30 days (protocol, TIMI, and GUSTO)
• Incidence of thrombocytopenia post index procedure and at 30 days
• Stent thrombosis (ARC definition) at 30 days
• Stroke at 30 days |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |