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 (REPEAT)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by Johann Wolfgang Goethe University Hospitals
Sponsor:
Information provided by (Responsible Party):
A. M. Zeiher, Johann Wolfgang Goethe University Hospitals
ClinicalTrials.gov Identifier:
NCT01693042
First received: September 19, 2012
Last updated: November 14, 2013
Last verified: November 2013
  Purpose

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


Condition Intervention Phase
Heart Failure
Biological: intracoronary infusion of autologous bone marrow-derived cells
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Johann Wolfgang Goethe University Hospitals:

Primary Outcome Measures:
  • Mortality at 2 years after inclusion into the study [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • Morbidity at 2 and 5 years after inclusion into the study [ Time Frame: 2 years and 5 years ] [ Designated as safety issue: Yes ]

    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



Estimated Enrollment: 676
Study Start Date: November 2013
Estimated Study Completion Date: January 2019
Estimated Primary Completion Date: November 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Single intracoronary cell application
Single intracoronary application of autologous bone marrow derived mononuclear cells
Biological: intracoronary infusion of autologous bone marrow-derived cells
Intracoronary infusion into open vessel / bypass supplying previous (> 3 months) infarct area
Other Name: t2c001
Active Comparator: repeated (2 times) intracoronary cell application
2 times (interval 4 months) intracoronary application of autologous bone marrow derived mononuclear cells
Biological: intracoronary infusion of autologous bone marrow-derived cells
Intracoronary infusion into open vessel / bypass supplying previous (> 3 months) infarct area
Other Name: t2c001

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01693042

Contacts
Contact: Andreas M Zeiher, MD +49 69 6301 ext 5789 zeiher@em.uni-frankfurt.de
Contact: Birgit Assmus, MD +49 69 6301 ext 7387 b.assmus@em.uni-frankfurt.de

Locations
Germany
Goethe University Frankfurt Not yet recruiting
Frankfurt, Germany, 60590
Contact: Andreas M Zeiher, MD    +49 69 6301 ext 5789    zeiher@em.uni-frankfurt.de   
Contact: Birgit Assmus, MD    +49 69 6301 ext 7387    b.assmus@em.uni-frankfurt.de   
Sub-Investigator: Birgit Assmus, MD         
Principal Investigator: Andreas M Zeiher, MD         
Goethe University; Cardiology Recruiting
Frankfurt, Germany, 60590
Contact: Birgit Assmus, MD    +49 69 6301 ext 7387    b.assmus@em.uni-frankfurt.de   
Principal Investigator: Andreas M Zeiher, MD         
Sub-Investigator: Birgit Assmus, MD         
Sponsors and Collaborators
Johann Wolfgang Goethe University Hospitals
Investigators
Principal Investigator: Andreas M Zeiher, MD Cardiology, Goethe University Frankfurt
Study Director: Birgit Assmus, MD Cardiology, Goethe University Frankfurt
  More Information

No publications provided

Responsible Party: A. M. Zeiher, Prof. Dr. Andreas M. Zeiher, Johann Wolfgang Goethe University Hospitals
ClinicalTrials.gov Identifier: NCT01693042     History of Changes
Other Study ID Numbers: 2011-01-01REPEAT, 2011-000595-33
Study First Received: September 19, 2012
Last Updated: November 14, 2013
Health Authority: Germany: Paul-Ehrlich-Institut

Keywords provided by Johann Wolfgang Goethe University Hospitals:
heart failure
old myocardial infarction
bone marrow-derived mononuclear cells
chronic
ischemic

Additional relevant MeSH terms:
Infarction
Heart Failure
Ischemia
Pathologic Processes
Necrosis
Heart Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on September 22, 2014