heart attack ST-elevation myocardial infarction
Conditions
Interventions
Intracoronary infusion of Stro-3 mesenchymal precursor cells after
revascularisation of the culprit coronary artery
Sponsors
Mesoblast Inc
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Subjects will be entered into this study only if they meet ALL of the following criteria: 1.*Willing and able to understand and sign the Informed Consent Form (ICF). 2.*Males or females >= 18 years. 3.*Clinical symptoms consistent with AMI (pain, etc.) for a maximum of 12 hours from onset of symptoms to completion of percutaneous coronary intervention (PCI). 4.*De novo anterior Acute Myocardial Infarct (AMI) defined as: *>= 0.2 mV ST elevation in 2 or more V1 - V6 leads with presentation in a maximum of 12 hours of onset of symptoms. Or: Presumed new left bundle branch block with a minimum of 0.1 mV concordant ST elevation with presentation in a maximum of 12 hours of onset of symptoms. And: Occlusion or flow limiting lesion with TIMI Flow Grade 0 or 1 in the left anterior descending (LAD) coronary artery. 5.*Successful revascularization of the culprit lesion in the LAD within a maximum of 12 hours from the onset of AMI symptoms defined as (1) primary percutaneous coronary intervention (PCI) with stent implantation, resulting in TIMI 3 or 2 flow AND (2) residual stenosis of less than 20% by on-line QCA. NOTE: Subject is eligible if in addition to requiring a primary PCI plus stenting for the culprit lesion they have a stenosis of the LAD that is both distinct from the culprit lesion and requires PCI at the time of the index cardiac catheterization procedure. For example, if the culprit lesion is in the mid LAD but there is also a high-grade first diagonal (D1) stenosis, then the latter lesion may undergo PCI (plus stenting) during the index catheterization This specifically excludes patients who may require a PCI to a non-LAD coronary artery during the index catheterization.;6.*If a female subject is of childbearing potential (i.e not amenorrheic for 12 or more months and/or not surgically sterile), the subject must be willing to use a highly effective method of contraception (oral, injectable or implanted hormonal methods of contraception, placement of an intrauterine device [IUD] or intrauterine system [IUS], condom or occlusive cap with spermicidal foam/gel/film/cream/suppository, male sterilization, or true abstinence) for at least 16 weeks after investigational agent infusion. 7.*Must be willing and able to return for required follow-up visits.
Exclusion criteria
Exclusion criteria: Subjects will not be enrolled into this study if they meet ANY of the following criteria: 1. Prior MI, known cardiomyopathy, or hospital admission for heart failure (HF) 2. Significant valvular disease (mitral or aortic valve regurgitation 3/4 classification as defined by ESC/ACC guidelines) 3. Unsuccessful revascularization of culprit artery defined as TIMI 1 or 0 flow or residual diameter stenosis of >= 20% by on line QCA analysis 4. Need for 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 infusion with the investigational agent. EXCEPT: Patients who present at the index catheterization with a need for a staged PCI of a non-LAD coronary artery will be eligible if: * *The staged PCI vessel does not have important collaterals to the LAD, and * *Agreement from the PI that the staged PCI can be safely scheduled after the day 30 cMRI has been determined by the Core cMR Imaging Laboratory to satisfy quality-control criteria. 5. Cardiogenic shock or hemodynamic instability within 24 hours prior to randomization, defined as the presence of any of the following: * Systolic blood pressure 120 bpm for more than 1 hour 6. Prior coronary artery bypass graft to the LAD 7. History of persistent atrial fibrillation 8. Prior PCI involving LAD 9. Malignancy within last 3 years from screening. The subject has had an active malignancy, within the past 3 years except for cervical carcinoma in situ and non-melanoma skin cancer that has been definitively treated 10. Acute or chronic bacterial or viral infectious disease 11. Pacemaker, ICD or any other contra-indication for cMRI. This is inclusive of patients with an MRI compatible device that was implanted prior to the potential qualifying event. 12. Known history of severe chronic obstructive pulmonary Disease (Forced Expiratory Volume (FEV1)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Feasibility endpoint: Feasibility of the infusion of the investigational agent will be monitored by measurement of TIMI flow and perfusion prior to, during (approximately 50% of total investigational agent volume infused), and following the investigational agent infusion after successful PCI and stenting. Primary Efficacy Endpoint: The primary efficacy endpoint is the change in LV end-systolic volume (LVESV) as assessed by cardiac MRI from baseline to 6 months post investigational agent infusion in each MPC treatment group compared with the Placebo group. Safety endpoint: All safety end points will be assessed from patient randomization through 24 months post investigational agent infusion: - Serious adverse events (SAEs) / adverse events (AEs) rates - Occurrence of MACCE including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and cardiac hospitalization due to heart failure. cardiac death, myocardial infarction, target vessel revascularization, stroke, new or worsening congestive heart failure during index hospitalization and cardiac hospitalizations due to congestive heart failure - Target vessel (or other vessel) revascularization post index cardiac catheterization and new or worsening heart failure during the index hospitalization will be tracked as "Adverse Events of Special Interest". - Total number of subjects with documented ventricular arrhythmia (sustained and non-sustained VT/VF) throughout the study period - Angina pectoris as defined by Canadian Cardiovascular Society (CCS) clinical clarification - New York Heart Association (NYHA) Class -Telemetry/48 hour Holter monitoring (during hospital admission and at 14 and 30 days, 3 and 6 months follow-up time points) with assessment of occurrence of ventricular arrythmia - TIMI flow and perfusion measurements following intracoronary infusion of the MPC cell solution compared with placebo - Physical examinations, monitoring of vital signs (heart rate, resp | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Efficacy Endpoints: - The change in LVESV as assessed by 2D-echocardiography from baseline to 6 months post investigational agent infusion. - The change in relative infarct size as assessed by late contrast enhancement MRI (% infarct volume/total LV tissue volume) from baseline to 6 months post investigational agent infusion. - Additional functional efficacy endpoints will be assessed with the following diagnostic studies: o Cardiac MRI at days 2-4 and 30; month 6 o LVEF o LV-ESV o LV-EDV o Left ventricular wall thickness and thickening in all segments including infarct area o Regional wall motion score o Myocardial microvascular obstruction measured as reduced signal intensity in the region of interest o MI size measured in the region of interest as late contrast enhancement o Myocardial salvage index o 2D echocardiogram at days 2-4 and 30; month 6 o LVEF o LVESV o LVEDV o Cardiac dimensions (LVESD/ LVEDD) o Regional wall motion score index - If there is no difference between the MPC groups (using a test with alpha = 0.1) in the effect on LVESV then the pooled MPC group will be compared to the Placebo group for all functional parameters. - A subset analysis that corresponds to the stratification used during randomization will be performed. Stratification will be based on the following categories defined as time from onset of AMI symptoms to PCI: o 2 to 6 to 6 to | — |
Countries
Netherlands
Outcome results
None listed