E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
non-ST and ST elevation acute coronary syndromes (ACS) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10011085 |
E.1.2 | Term | Ischaemic coronary artery disorders |
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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 |
The primary objective of this study is to test that AZD6410 is superior to clopidogrel for prevention of vascular events (death from vascular causes, MI, stroke) in patients with non-ST or ST elevation acute coronary syndromes (ACS). |
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E.2.2 | Secondary objectives of the trial |
- To assess the safety and tolerability of AZD6140 compared to clopidogrel. - To assess the efficacy and safety of AZD6140 and clopidogrel in those patients undergoing coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI) during the study. - To assess the occurrence of arrhythmic episodes detected by Holter monitoring during the initial period after randomization and at one month.
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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 |
ECG substudy (same date as main study protocol) Objectives: To assess whether ST-T changes at hospital entry modulate AZD6410 treatment effect. To analyse whether ST changes in combination with biomarkers improve patient risk stratification over biomarkers alone. To assess differences between AZD6410 and clopidogrel treatment on ECG patterns at hospital discharge.
Blood core substudy (same date as main study protocol) Objectives: To follow biomarkers over time and identify differences between AZD6410 and clopidogrel treated groups. To find correlations between clinical outcomes in these groups and biomarker levels at hospital entry, and at discharge or at one month. To assess the influence of the genetic constitution of AZD6140 treated patients on clinical outcomes and biomarker levels. To employ integrated proteomic and metabolomic and cellular analyses as candidate and discovery biomarkers for predicting clinical outcomes and drug safety. To investigate whether advanced biomarkers can predict drug safety and efficacy. To determine the prognostic value of advanced biomarkers.
Angiography substudy (same date as main study protocol) Objective: investigate if the use of AZD6140 will be associated with further improvements in flow and perfusion on coronary angiography in the setting of ACS.
Health economics and quality of life substudy (same date as main study protocol) Objectives: to estimate the incremental cost effectiveness ratio of AZD6410 compared to clopidogrel in patients with ACS.
Genetic research (same date as main study protocol) Objectives: To obtain DNA samples for future exploratory research on the effects of genetic polymorphisms on i) the response to AZD6410 and clopidogrel, ii) the disposition of AZD6410 and clopidogrel and iii) the susceptibility to and prognosis of ACS under study
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E.3 | Principal inclusion criteria |
1. Index event of non-ST or ST segment elevation ACS. The patient should be hospitalised for chest pain and potential ACS and the onset of the most recent cardiac ischaemic symptoms of the index event must occur within the 24 hours before randomisation and be documented by cardiac ischaemic symptoms of ≥10 minutes duration at rest AND (i, ii, or iii):
i) Persistent ST segment elevation ≥1mm (0.1 mV) in 2 or more contiguous leads and primary PCI planned OR ii) New or presumed new left bundle branch block (LBBB) and primary PCI planned OR iii) Cardiac ischaemic symptoms of ≥10 minutes duration at rest and at least 2 of the following 3 criteria (A-C):
A) ST segment changes on ECG indicative of ischaemia B) Positive biomarker (Troponin I or -T or CK-MB) evidence of myocardial necrosis C) Having at least one of the following risk factors: Aged 60 or over, Previous MI or CABG, Known multi-vessel coronary artery disease (CAD), Previous ischaemic stroke, TIA, carotid stenosis, or cerebral revascularisation, Diabetes mellitus, Peripheral arterial disease, Chronic renal dysfunction
2. Provision of signed informed consent form. 3. Male or female aged at least 18 years 4. Females of child-bearing potential who are willing to use 2 methods of contraception.
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E.4 | Principal exclusion criteria |
1. Contraindication or other reason that clopidogrel or AZD6140 should not be administered. 2. Index event is a complication of PCI 3. Patient has undergone PCI after the index event and before the first dose of study treatment 4. Oral anticoagulation therapy that cannot be stopped 5. Fibrinolytic therapy in the 24 hours prior to randomisation, or planned fibrinolytic treatment following randomisation 6. Increased risk of bradycardic events 7. Patient requires dialysis 8. Platelet count less than 100 x 10E9/L 9. Haemoglobin (Hb) level less than 100 g/L 10. Participation in another investigational drug or device study in the last 30 days 11. Pregnancy or lactation 12. Concomitant oral or intravenous therapy with strong CYP 3A inhibitors, CYP3A substrates with narrow therapeutic indices, or strong CYP3A inducers which cannot be stopped for the course of the study 13. Any other condition which in the opinion of the investigator, may either put the patient at risk or influence the result of the study 14. Involvement in the planning and conduct of the study 15. Previous enrolment or randomisation of treatment in the present study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to the first occurrence of any event from the composite of death from vascular causes(*), myocardial infarction and stroke. (*): Death from vascular causes includes CV deaths, cerebrovascular deaths, and any other death for which there was no clearly documented non-vascular cause.
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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 | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Quality of life - Patient reported outcomes |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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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.8.3 |
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 | 14 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 1000 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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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End of study is defined as date of database lock which is the timepoint after which no patient will be exposed to study-related activities. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |