Repeated application of bone marrow-derived stem cells to treat chronic post-infarction heart failure

• Register: EUCTR
• Last refreshed on: 11 January 2016
• Main ID: EUCTR2011-000595-33-NL
• Date of registration: 19/11/2015
• Prospective Registration: Yes
• Primary sponsor: Goethe University Frankfurt
• Public title: Repeated application of bone marrow-derived stem cells to treat chronic post-infarction heart failure
• Scientific 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 REpetitive Progenitor cEll therapy in Advanced chronic hearT failure (REPEAT trial) - REPEAT
• Date of first enrolment: 17/12/2015
• Target sample size: 676
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-000595-33
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: single versus sequentential treatment Number of treatment arms in the trial: 2

Countries of recruitment

Germany, Netherlands

Contacts

• Name: Cardiology
• Affiliation: Goethe University

• Name: Cardiology
• Affiliation: Goethe University

Key inclusion & exclusion 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
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 176
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 500

Exclusion criteria:
• Non-ischemic cardiomyopathy
• Necessity for revascularization in other vessel than the infarct vessel
at the time of study therapy
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• 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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Chronic post-infarction heart failure due to an at least 3 months old myocardial infarction, treated with optimal medication according to the evidence-based guidelines, in NYHA stadium II-III; and with open vessel / bypass sullpying the previously infarcted area

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Intervention(s)

Product Name: t2c001
Product Code: t2c001
Pharmaceutical Form: Solution for infusion

Primary Outcome(s)

Main Objective: Improve mortality in patients with symptomatic chronic post-infarction heart failure under full dose conventional medical and device treatment
including resynchronization therapy frequently by intracoronary infusion of autologous bone marrow-derived mononuclear cells.

Primary end point(s): 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 Objective: Improve morbidity in patients with symptomatic chronic post-infarction heart failure under full dose conventional medical and device treatment including resynchronization therapy frequently by intracoronary infusion of autologous bone marrow-derived mononuclear cells.

Timepoint(s) of evaluation of this end point: 2 years after inclusion into the trial

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 2 years after inclusion into the trial

Secondary end point(s): Efficacy endpoints:
- In patients receiving 2 repeated intracoronary applications of
autologous bone marrow-derived cells (t2c001), the observed mortality
is significantly lower than the SHFM-predicted mortality at 2-year followup
Comparison between the 2 treatment groups at 2-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
Prespecified combined clinical endpoints:
o Death and rehospitalisation for heart failure
o Cardiac Death and rehospitalisation for heart failure
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o Cardiac and Cardiovascular Death and rehospitalisation for heart
failure
o Death and myocardial infarction
o Death and myocardial infarction and rehospitalisation for heart failure
o Death and myocardial infarction and revascularization
o Death and any cardiovascular event
Safety endpoints:
- Life-threatening arrhythmias (sustained ventricular tachycardia;
ventricular fibrillation and cardiopulmonary resuscitation)
- Any new malignant disease
- Bleeding events
- Safety of intracoronary application of autologous bone marrow-derived
cells (t2c001) (procedural complications, adverse events at 30 days and
4 months after application, SAEs at 1 and 2 years)

Secondary ID(s)

2011-000595-33-DE

2011-01-01REPEAT

Source(s) of Monetary Support

Goethe University Frankfurt