E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
patients with ST-elevation myocardial infarction |
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MedDRA Classification |
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 assess safety and feasibility of adipose-derived stem cells delivered via the intracoronary (IC) route in the treatment of patients with ST-elevation myocardial infarction (STEMI) at 6 months |
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E.2.2 | Secondary objectives of the trial |
Additional assessments of left ventricular function will be performed at 12, 18, 24, and 36 months after the procedure. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Able to provide informed consent 2.Males or females 20 to 85 years of age, inclusive 3·Clinical symptoms consistent with AMI (pain, etc.) for a minimum of 2 and a maximum of 12 hours from onset of symptoms to PCI, and unresponsive to nitroglycerin 4·AMI 5·Anterior AMI: ·≥ 0.2 mV ST elevation in 2 or more V1 – V6 leads AND interval complaints and first contact < 12 hours or 6·Inferior AMI:≥ 0.1 mV ST elevation in 2 or more leads II, III, aVF AND interval complaints and first contact < 12 hours or 7·New left bundle branch block: with interval symptoms and first contact < 12 hours or 8·Cardiac enzymes: Two times the upper limit of normal of creatine kinase with an abnormal level of creatine kinase MB fraction 9·Successful revascularization of the culprit lesion in the major epicardial vessel within 12 hours of the onset of AMI symptoms (defined as (1) primary or facilitated PCI with stent implantation, resulting in TIMI 3 flow AND (2) residual stenosis no more than 10% by visual assessment or no more than 20% by on-line QCA) 10·Area of hypo- or akinesia corresponding to the culprit lesion, as determined by left ventriculogram at the time of primary PCI 11·Left ventricular ejection fraction (LVEF) ³30% and £50%; as determined by left ventricular angiography after PCI. LVEF may be assessed by echocardiography if the left ventricular angiogram is not analyzable or available. 12·Ability to undergo liposuction 13·Negative urine pregnancy test (females only).
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E.4 | Principal exclusion criteria |
1·Prior MI, prior known cardiomyopathy, or prior hospital admission for congestive heart failure (CHF) 2·More than 24 hours after acute PCI 3·Significant valvular disease 4·More than 12 or less than 2 hours between the onset of first symptoms of AMI and revascularization, defined as restoration of at least TIMI 3 flow 5·Inability to complete ADRC infusion within 24 hours of PCI 6·Staged treatment of coronary artery disease, or other interventional or surgical procedures to treat heart disease (e.g., valve replacement, PCI or CABG) planned or scheduled within 6 months after the study procedure 7·Need for mechanical ventilation 8·Cardiogenic shock 9·Hemodynamic instability within 24 hours prior to randomization, defined as the presence of any of the following: 10·Need for inotropic support 11·Systolic blood pressure <90 mmHg 12·Heart rate >100 bpm for more than 1 hour 13·Prior ventricular fibrillation or sustained ventricular tachycardia 14·Persistent atrial fibrillation 15·Neoplasia 16·Acute or chronic bacterial or viral infectious disease 17·Pacemaker, ICD or any other contra-indication for MRI 18·LVEF <30% or >50% as determined by left ventriculogram at the time of primary PCI 19·Moderate or severe COPD (refer to Appendix 16 for classification codes) 20·Pregnant and/or nursing females 21.Known relevant allergies or sensitivities 22·Serum creatinine >2.0 mg/dL 23·Participation in any other clinical research study that has not reached the primary efficacy endpoint or otherwise would interfere with the patient’s participation in this study 24·Life expectancy <1 year 25·Any concurrent disease or condition that, in the opinion of the investigator, would make the patient unsuitable for participation in the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety endpoints will be assessed at 30 days, and at 3, 6, 12, 18, 24, and 36 months post procedure: ·Major adverse cardiac or cerebral event (MACCE) rates ·Serious adverse events (SAEs) / adverse events (AEs) rates ·Composite clinical endpoint: death, MI, stroke ·Re-hospitalization for heart failure ·Angina pectoris as defined by Canadian Cardiovascular Society (CCS) & Braunwrad Classifications ·New York Heart Association (NYHA) Class ·Continuous Electrocardiographic monitoring for 6 days following procedure (72 hours by telemetry and 72 hours by Holter monitor), then weekly for the first four weeks (for 48 hours) and at 2 , 3, 4 , 6, 12, 18, 24 and 36 months (for 24 hours).
Feasibility endpoints will be assessed at the time points specified in Appendix 17 and include the following: ·Absolute LVEF and change in LVEF from baseline to six months (by 2D & 3D echocardiography, LV angiography and MRI 17-segment AHA model) ·MI size (by delayed enhancement in MRI 17-segment AHA model) ·Regional wall thickness and thickening in all segments including infarct area (by MRI 17-segment AHA model)31 ·LV-ESV and LV-EDV (by MRI 17-segment AHA model) ·Absolute and change in perfusion defect after revascularization to six months (by SPECT imaging) ·Wall Motion Score Index (by 2-D echocardiography).
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
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 | Information not present in EudraCT |
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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Primary outcomes of this trial will be assessed at six (6) months post index procedure. After the 6-month assessments, long-term patient follow up will continue for an additional 30 months. |
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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 | |
E.8.9.1 | In the Member State concerned months | 36 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 36 |