E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute ST-segment Elevation Myocardial Infarction |
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E.1.1.1 | Medical condition in easily understood language |
Heart attack where the coronary artery is completely blocked off by the blood clot, and as a result virtually all the heart muscle being supplied by the affected artery starts to die. |
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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 | 14.1 |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10000891 |
E.1.2 | Term | Acute myocardial infarction |
E.1.2 | System Organ Class | 10007541 - Cardiac 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 principal objective of our proposed study is to determine:- 1) Whether adjunctive medical treatment given via a very small tube placed beyond the blockage downstream in the affected heart attack artery at time of angioplasty for heart attack and following blood clot removal from the heart vessel, reduces downstream small blood vessel obstruction and heart muscle damage size as determined by using CMR scanners. The principal study question is: 1) How might we attenuate small blood vessel obstruction and thus reduce heart attack size in patients undergoing angioplasty for heart attack?
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of our proposed study are to determine:- 1) Whether there is a difference between the small downstream artery dilating drugs -adenosine and sodium nitroprusside in their ability to reduce small blood vessel obstruction and heart muscle damage size determined using CMR scanners, both given via a very small tube (catheter) placed beyond the blockage in the downstream affected heart artery. 2) The correlation of markers of poor blood flow in heart vessels as determined by the flow seen on the angiogram, with CMR detected small blood vessel obstruction and heart muscle damage, as well as with clinical outcome at six months. The secondary study questions are: 1) Should all,some or no patients receive adjunctive therapies (adenosine / sodium nitroprusside) given via a small tube (catheter) to reduce small downstream blood vessel obstruction routinely in addition to the standard current treatment of blood clots removal(aspiration) from the heart's artery and if so |
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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 |
Title:Assessment of platelet activation and inflammation during the procedures. See Full protocol Version 5, Date: 04/11/11, Page 14.
This mechanistic sub-study will be carried out on patients entered into the study at Glenfield hospital (Leicester), and will be performed in Professor Goodall’s laboratory by the Clinical Fellow, using established methods, and with support from experienced technical staff.
Objective: Small samples of blood (≤2ml) will be taken from the patients to assess the effect of these short lived treatment agents on platelet activation within the coronary circulation.
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E.3 | Principal inclusion criteria |
• ≥ 18 years age with written informed ASSENT prior to angiography. (ASSENT is being used following Ethical Committee approval in another trial run by University Hospitals of Leicester- The STREAM study). • ST – segment elevation myocardial infarction (STEMI) ≤ 6 hrs of symptom onset requiring primary reperfusion by PCI. • Single-vessel and coronary artery disease (non culprit disease ≤70% stenosis at angiography) to avoid bias which may occur in analysis of microvascular obstruction (MVO) and infarct size if intervention should be undertaken in more than one vessel. • TIMI flow 0/I at angiography.
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E.4 | Principal exclusion criteria |
• Any exclusion criteria for primary percutaneous coronary intervention (P-PCI) (see below). • Previous Q wave myocardial infarction. • Contraindications to cardiac MRI contrast agents, or study medications: Aspirin, Prasugrel, Bivalirudin. • Cardiogenic Shock or systolic blood pressure ≤ 90mmHg needing intraortic balloon pump. • Culprit lesion located in a by-pass graft. • Culprit lesion non identified. • Stent thrombosis. • Left main disease. • Known severe asthma. • Known stage 4 or 5 chronic kidney disease (eGFR<30ml/min). • Pregnancy. Exclusion criteria for P-PCI: presentation timing, inadequate arterial access, patient unable to tolerate PCI procedure(in operators’ opinion). Absolute contra-indication to cardiac MRI (Pacemaker, Implantable cardiac defibrillator, intra-cranial metal clips).
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E.5 End points |
E.5.1 | Primary end point(s) |
Cardiac magnetic resonance (CMR) measured infarct size (%LV mass) at 48-72 hours post procedure. Infarct size has been chosen rather than the microvascular obstruction (MVO) as the primary end point since there is a wealth of published data on infarct size following P-PCI. We are also uncertain as to the expected size of effect on MVO (incidence and absolute reduction in MVO as % of LV mass) of both sodium nitroprusside and adenosine. MVO and infarct size measured on CMR are closely inter-related and are both important predictors of prognosis. |
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E.5.2 | Secondary end point(s) |
1. CMR incidence and extent of MVO (% LV mass)at 48-72 hours post procedure. 2. CMR measured myocardial salvage index, haemorrhage, LV EF and volumes in the acute stage. 3. Angiographic markers of MVO including the recently designed computer-assisted myocardial blush quantification ‘Quantitative Blush Evaluator’ (QuBE)(83). (Assessed by two interventional cardiologists blinded to treatment arm). 4. Incidence pre and post procedure angiographic true “no-reflow”. 5. Incidence of angiographic slow/no-reflow after PCI with the three different management strategies. 6. Any in-patient clinical events (re-occlusion), need for repeat PCI, recurrent chest pain with new ECG changes, incidence of clinical heart failure (symptoms plus basal crackles plus X-ray evidence pulmonary congestion) proven cerebrovascular accident (CVA). 7. Overall MACCE and its components at 6 months: namely death, need for TLR, recurrent MI, severe heart failure, and CVA. 8. Comparing CMR markers with other myocardial perfusion markers: angiographic (TIMI grade CTFC, MBG, and computer-assisted myocardial blush quantification), ECG (ST segment resolution) and cardiac enzymes. 9. Degree of ST resolution. 10. Echocardiography assessment of LV (EDV, ESV and EF) at 8-12 weeks during a routine follow up visit.
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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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 | 2 |
E.8.5 | The trial involves multiple Member States | No |
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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last patient last visit / telephone interview |
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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 | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |