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
Trial Snapshot
- Phase
- Phase 2
- Status
- Active, not recruiting
- Sponsor
- Enrollment
- 81
- Locations
- 6
- Primary Endpoint
- Mortality at 2 years after inclusion into the study
Study Overview
Brief Summary
Single or repeated application of autologous bone marrow-derived stem cells to treat chronic post-infarction heart failure
Detailed Description
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Single intracoronary cell application
Single intracoronary application of autologous bone marrow derived mononuclear cells
Intervention: intracoronary infusion of autologous bone marrow-derived cells (Biological)
repeated (2 times) intracoronary cell application
2 times (interval 4 months) intracoronary application of autologous bone marrow derived mononuclear cells
Intervention: intracoronary infusion of autologous bone marrow-derived cells (Biological)
Outcomes
Primary Outcomes
Mortality at 2 years after inclusion into the study
Time Frame: 2 years
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)
Secondary Outcomes
- Morbidity at 2 and 5 years after inclusion into the study(2 years and 5 years)
Investigators
A. M. Zeiher
Prof. Dr. Andreas M. Zeiher
Johann Wolfgang Goethe University Hospital