E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Myocardial Infarction with reduced Left Ventricular ejection fraction |
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E.1.1.1 | Medical condition in easily understood language |
Heart attack resulting in reduced pumping capacity of the heart |
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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 | 19.1 |
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 aim of the study is to assess if the administration of a single injection of patient's own bone marrow derived stem cells into their coronary arteries will reduce all cause mortality. |
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E.2.2 | Secondary objectives of the trial |
Looking at the time from randomisation to cardiac and cardiovascular events including cardiac death. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed and dated informed consent 2. Men and women of any ethnic origin aged ≥ 18 years 3. Patients with acute STelevation (including new LBBB) myocardial infarction as defined by the universal definition of AMI. 4. Successful acute reperfusion therapy (residual stenosis visually <50% and TIMI flow ≥2) within 24 hours of symptom onset or thrombolysis within 12 hours of symptom onset followed by successful percutaneous coronary intervention (PCI) within 24 hours after thrombolysis 5. Left ventricular ejection fraction ≤ 45% with significant regional wall motion abnormality assessed by quantitative echocardiography (central, independent core lab analysis) 3 to 6 days after reperfusion therapy 6. Open coronary artery suitable for cell infusion supplying the target area of abnormal wall motion |
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E.4 | Principal exclusion criteria |
1. Participation in another clinical trial within 30 days prior to randomisation unless non interventional trials or trials where patients are randomised to only standard care and this has been discussed and agreed with the CI/sponsor prior to consenting. 2. Previously received stem/progenitor cell therapy 3. Pregnant or nursing women 4. Mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study or to follow the protocol 5. Necessity to revascularise additional vessels, outside the target coronary artery at the time of BMMNC infusion (additional revascularisations after primary PCI and before BMMNC cell infusion are allowed), unless clinically indicated and according to latest guidelines. this decision should be made at the time of the index procedure and explicitly stated at the time 6. Cardiogenic shock requiring mechanical support 7. Platelet count <100,000/μl, or hemoglobin <8.5 g/dl 8. Impaired renal function, i.e. serum creatinine >2.5 mg/dl 9. Persistent fever or diarrhea not responsive to treatment within 4 weeks prior screening 10. Clinically significant bleeding within 3 months prior screening 11. Uncontrolled hypertension (systolic >180 mmHg and diastolic >120 mmHg) 12. Life expectancy of less than 2 years from any noncardiac cause or neoplastic disease |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time from Randomisation to all-cause-death |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The outcome will be assessed at 30 days and every 3 months until the end of the study or up to two years after randomisation with a minimum of 2 years follow up. |
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E.5.2 | Secondary end point(s) |
Time from randomisation to cardiac death Time from randomisation to cardiovascular death or rehospitalisation due to heart failure Time from randomisation to cardiovascular rehospitalisation for: Recurrent myocardial infarction Coronary revascularization procedures Heart Failure Unplanned implantation of implantable cardioverter defibrillator (ICD)/cardiac resynchronisation therapy (CRT) device after the initial hospitalisation discharge Stroke Safety endpoints are: Incidence of adverse events Incidence of bleeding by bleeding academic research consortium (BARC) definitions Incidence of syncopes Incidence of arrhythmias (atrial fibrillation/ventricular tachycardia) Incidence of neoplastic diseases |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The outcome will be assessed at 30 days and every 3 months until the end of the study or up to two years after randomisation with a minimum of 2 years follow up. |
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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 | No |
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 |
unspecified control group |
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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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
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 | 6 |
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 | 6 |
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 |