E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Myocardial Infarction with reduced Left Ventricular ejection fraction |
|
E.1.1.1 | Medical condition in easily understood language |
Heart attack resulting in reduced pumping capacity of the heart |
|
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 | 18.1 |
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 |
|
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. |
|
E.2.2 | Secondary objectives of the trial |
Looking at the time from randomisation to cardiac and cardiovascular events including cardiac death. |
|
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
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 |
|
E.4 | Principal exclusion criteria |
1. Participation in another clinical trial within 30 days prior to randomisation
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)
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 |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Time from Randomisation to all-cause-death |
|
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. |
|
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 |
|
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. |
|
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 |
|
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
|
This trial is designed as an event-driven trial. The study will be terminated after 450 events have been observed and this is estimated to happen at 2 year follow up for a total of 3000 patients recruited. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
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 | 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 |