Acute Myocardial Infarction (AMI): "First STEMI submitted to elective primary PCI with successful revascularization (TIMI ? 2), but intermediate-high risk of HF development (infarct size by MRI>25%"
Conditions
Interventions
Product Code: AlloCSC-01
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: NA
Other descriptive name: Cardioblastos troncales adultos alogénicos humanos cardíacos expandidos // Human
Sponsors
Coretherapix S.L.U.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Adult patients ? 18 years of age and ? 80 years. 2. Patients presenting a ST-segment-elevation in the acute myocardial infarction (STEMI) according to the universally accepted definition founded in the STEMI management guide of the European Society of Cardiology 3. Killip ? 2 on admission 4. Successful primary percutaneous coronary intervention (PCI) (Thrombolysis In Myocardial Infarction [TIMI] = 3) during the first 12h after infarct symptoms 5. Bare-metal stent at primary PCI 6. Ejection Fraction (EF) ?45% analyzed by echocardiography at day 2 after primary PCI 7. Ejection Fraction (EF) ?45% analyzed by magnetic resonance imaging (MRI). This MRI will be done between day 3 and day 7 after infarction. 8. Patients with an infarct size in left ventricle (LV) ?25% tested in the first MRI will be included. 9. The affected coronary artery must be adequate for cells infusion by catheterization. 10. The presence of microvascular obstruction at inclusion MRI is permitted 11. The patient is stable and in adequate clinical condition to undergo the administration of the cell medicine through a second catheterization, between 4-7 days after the first PCI. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: 1. Participation in another clinical trial in the last 30 days 2. Has previously received cell or gene therapy 3. Women who are pregnant or breastfeeding 4. Mental disease or psychological condition that impedes the subject from understanding the nature of the protocol and granting his/her consent 5. Previous Q-wave infarction 6. Valve disease, relapsing pericarditis, history of cardiac tamponade, cardiomyopathies 7. Involvement of coronary trunk 8. Severe stenotic lesion (>90%) in a coronary vessel with size >2.75mm, shown in the first PCI and non revascularizable during primary PCI 9. Admission for prior HF or EF 2 before STEMI 10. Killip >2 on admission 11. History of sustained VT or VF at any point since hospital admission 12. Sustained VT that does not revert with treatment or requires >6 hours to be controlled in the 48 hours prior to the product administration procedure 13. Complete Auriculo Ventricular blockade on arrival to the Emergency Room (previously unknown), or acute branch block during hospitalization 14. History of cardioembolic disease 15. Platelets <100,000 and/or Hb<8.5g/dL 16. Acute or chronic renal failure with creatinine ?2.5 or creatinine clearance ?50 mL/min 17. Infection with systemic involvement (fever or documented Systemic Inflammatory Response Syndrome) current and/or in the month prior to AMI 18. History of bleeding in the 3 months prior to screening in any location due to uncontrolled coagulopathy 19. Cancer disease, except that eradicated at least 5 years before inclusion, and without receiving radiotherapy on chest. It is permitted coetaneous non-melanoma neoplasms completely eliminated (at any time) and that do not require subsequent chemotherapy or radiotherapy on chest. 20. Child's C stage chronic liver disease 21. Stroke in the previous 12 months 22. Baseline respiratory failure and/or requires oxygen at home 23. Advanced dementia according to the Barthel index 24. History of autoimmune disease and/or positive autoantibodies at least double titer of the normal ranges 25. Patients with Hepatitis B virus (HBV), Hepatitis C virus (HCV), Human Immunodeficiency virus (HIV) or asymptomatic carriers (positive without clinical disease) except positive for HBV by vaccination 26. Uncontrolled hypertension at screening despite treatment (systolic blood pressure [BP] ? 180 and/or diastolic BP ? 110) 27. Very poorly controlled diabetes (Hb1Ac ?8.5 g/dL) or with serious target organ lesion (peripheral vascular disease requiring revascularization or non revascularizable, CRF with creatinine clearance ?50 mL/min, stroke in the previous 12 months, severe non-revascularizable coronary disease) 28. Primary or acquired immune deficiency or immunosuppressant treatment (including treatments with immunosuppressants in the previous three months or with systemic corticosteroids in the previous month or foreseeable need for those treatments during the course of the study). 29. Very poorly controlled hypercholesterolemia (total cholesterol ?250 mg/dL despite treatment) 30. Active smoking greater than or equal to 40 cigarettes/day 31. Recreational drug use that would hamper heart or cardiovascular function, at least once in the past 6 months 32. Weekly alcohol consumption over 80 g per kg 33. Women of childbearing potential who do not agree to use contraceptives during the study period and up to 6 months afterwards 34. Life expectancy of less than 2 years for any reason. 35
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective consists in the evaluation of the safety of the treatment: - In the dose escalation phase the principal objective is to evaluate the safety and feasibility of the procedure (MRI and administration method) that is not part of the routine care of a heart attack, and confirm that the target dose can be administered intracoronary in a safe way. The following will be assessed: o Deaths from any cause within 30 days o Adverse Events (AEs) of any nature observed from magnetic resonance imaging (MRI) of patient inclusion to up to 7 days after treatment administration. - In the randomization phase, the Major Adverse Cardiac Events (MACE) will be assessed for the first 30 days of treatment administration, defined as death from any cause, new myocardial infarction, hospitalization for failure heart, ventricular tachycardia (VT), ventricular fibrillation (VF) and stroke.;Secondary Objective: FOLLOW-UP SAFETY: MACE in the first 6 months and at 12 months. Death from any cause. Death from cardiovascular cause. General monitoring of all serious adverse events from any cause. EFFICACY: Evolution of infarct (morphology): % change in MRI at 6 and 12 months after treatment administration vs. screening MRI and 1 month MRI. Compare CSC versus placebo. Evolution of edema: % change in MRI at 1 month after treatment administration vs screening MRI. Evolution of the biomechanical parameters by MRI: % changes of MRI at 6 and 12 months of administration of the treatment vs screening MRI and 1 month MRI. Compare CSC vs placebo. CLINICAL PARAMETERS OF ANALYSIS: ProBNP curve (one day prior to 2nd hemodynamic assessment, 6 months, 12 months). CRP (one day prior to 2nd hemodynamic assessment, at discharge, 1 month). 6 minute walking test at discharge, 6 and 12 months. NYHA at discharge, 6 and 12 months. MLHFQ at discharge, 6 and 12 months. Hospital admission for HF. CCV mortality.;Timepoint(s) of evaluation of this end point: Daily assessment of sa | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy Variables: 1. Evolution of infarct size comparing the percentage of change with respect to the LV. The analysis will be performed by MRI at 6 and 12 months after treatment administration versus screening MRI and 1 month MRI. 2. Evolution of edema: comparing the percentage of change at 1 month after treatment administration versus edema at the moment of the screening. The analysis will be by MRI. 3. Evolution of the biomechanical parameters comparing the percentage of changes at 6 and 12 months after administration of the treatment versus the ones at the moment of the screening or at month 1 after the administration. The analysis will be by MRI. All analysis will be performed by comparing the population treated with CSCs versus the one treated with placebo. Clinical Parameters: 1. BNP curve. Comparing the BNP levels one day prior to the PCI of administration and 6 and 12 months after treatment. 2. CRP: comparing the CRP levels one day prior to the PCI of administration, at hospital discharge, and 1 month after treatment 3. 6 minute walking test at hospital discharge and 6 and 12 months after treatment 4. NYHA classification at hospital discharge and 6 and 12 months after treatment 5. MLHFQ at hospital discharge and 6 and 12 months after treatment 6. Hospital admission for HF during the 12 months of the clinical trial will be registered. 7. Follow-up of all the cases of cardiovascular mortality during the whole clinical trial. All analysis will be performed by comparing the population treated with CSCs versus the one treated with placebo.;Timepoint(s) of evaluation of this end point: First month and 6 and 12 months. | — |
Countries
Belgium, Spain
Contacts
Public ContactClinical Trial Information Desk
Coretherapix
Outcome results
None listed