Compare the Effects of Single Versus Repeated Intracoronary Application of Autologous Bone Marrow-derived Mononuclear Cells on Mortality in Patients With Chronic Post-infarction Heart Failure

Study Overview
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Brief Summary
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Single or repeated application of autologous bone marrow-derived stem cells to treat chronic post-infarction heart failure

Detailed Description
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Improve mortality and morbidity in patients with symptomatic chronic post-infarction heart failure under full dose conventional medical and device treatment including resynchronization therapy, by single versus repeated intracoronary infusion of autologous bone marrow-derived mononuclear cells.

Official Title
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Randomized Controlled Trial to Compare the Effects of Single Versus Repeated Intracoronary Application of Autologous Bone Marrow-derived Mononuclear Cells on Total and SHFM-predicted Mortality in Patients With Chronic Post-infarction Heart Failure

Conditions
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Heart Failure

Intervention / Treatment
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* Biological: intracoronary infusion of autologous bone marrow-derived cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Previous myocardial infarction at least 3 months ago, open infarct vessel or bypass Left ventricular ejection fraction (LVEF) ≤ 45% on echocardiography Stable chronic heart failure NYHA class II to III under constant (4 weeks) evidence-based optimal medical treatment age 18 - 80 years written informed consent women of childbearing age: negative pregnancy test; effective contraception for the first 8 months in the trial Exclusion Criteria: Non-ischemic cardiomyopathy Necessity for revascularization in other vessel than the infarct vessel at the time of study therapy Hemodynamic relevant severe valvular disease with indication for operative / interventional revision Heart failure with preserved ejection fraction (diastolic heart failure), LVEF > 45% Unstable Angina Severe peripheral artery occlusive disease (≥ Fontaine stadium III) Active infection (C-reactive protein > 10 mg/dl), chronic active hepatitis; any chronic inflammatory disease, HIV infection Neoplastic disease without documented remission in the last 5 years Stroke ≤ 3 months Impaired renal function (Serum creatinine > 2,5 mg/dl) at the time of study inclusion Relevant liver disease (GOT > 2x upper normal limit, spontaneous INR > 1,5). Diseases of hematopoetic system, anemia (Hemoglobin < 8.5 mg/dl), thrombocytopenia < 100.000/µl) Splenomegaly Allergy or intolerance of clopidogrel, prasugrel, ticagrelor, heparin, bivalirudin History of bleeding disorder gastrointestinal bleeding ≤ 3 months major surgery or trauma ≤ 3 months Uncontrolled hypertension Pregnancy, lactation period mental retardation previous cardiac cell therapy within last 12 months Participation in another clinical trial ≤ 30 days

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Single intracoronary cell application<br>Single intracoronary application of autologous bone marrow derived mononuclear cells | Biological: intracoronary infusion of autologous bone marrow-derived cells<br>* Intracoronary infusion into open vessel / bypass supplying previous (> 3 months) infarct area<br>* Other names: t2c001;|
| Active Comparator: repeated (2 times) intracoronary cell application<br>2 times (interval 4 months) intracoronary application of autologous bone marrow derived mononuclear cells | Biological: intracoronary infusion of autologous bone marrow-derived cells<br>* Intracoronary infusion into open vessel / bypass supplying previous (> 3 months) infarct area<br>* Other names: t2c001;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality at 2 years after inclusion into the study | 2-year observed mortality is significantly lower in patients receiving 2 repeated intracoronary applications of autologous bone marrow-derived cells (t2c001) compared to patients receiving 1 intracoronary application of autologous bone marrow-derived cells (t2c001) | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Morbidity at 2 and 5 years after inclusion into the study | Efficacy endpoints: Comparison between the 2 treatment groups at 2-year and 5-year follow-up Cardiac mortality, cardiovascular mortality Rehospitalisation for heart failure Ischemic cardiac events (STEMI, NSTEMI, ACS) Coronary revascularisations (PCI / CABG) Heart transplantation, Assist-device implantation New resynchronization therapy, ICD implantation NYHA-Status, NT-proBNP serum levels Minnesota Living with Heart Failure Questionnaire Safety endpoints: bleeding events, all in-hospital events (during hospitalization for BMC therapy), life-threatening arrhythmias, new malignancies | 2 years and 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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heart failure, old myocardial infarction, bone marrow-derived mononuclear cells, chronic, ischemic