E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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 |
|
E.1.1.1 | Medical condition in easily understood language |
Chronic heart failure due to a recent heart attack |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
|
E.2.2 | Secondary objectives of the trial |
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. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 |
|
E.4 | Principal 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 |
|
E.5 End points |
E.5.1 | 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) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
2 years after inclusion into the trial |
|
E.5.2 | 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) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
2 years after inclusion into the trial |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
single versus sequentential treatment |
|
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |