The current randomized controlled trial should investigatewhether- 2 sequential intracoronary BM-MNC applications are associated with a lower mortality than oneintracoronary BM-MNC application- 2 intracoronary treatments with BM-MNC are associated…
ID
Source
Brief title
Condition
- Heart failures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
2-year total mortality is significantly lower in patients receiving 2 repeated
intracoronary applications of autologous bone marrow-derived progenitor cells
(t2c001) compared to patients receiving 1 intracoronary application of
autologous bone marrow-derived progenitor cells (t2c001).
Secondary outcome
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 follow-up.
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
* Prespecified combined clinical endpoints:
o Death and rehospitalisation for heart failure
o Cardiac Death and rehospitalisation for heart failure
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 any cardiovascular event
All in-hospital events (during hospitalization for cell therapy)
* Life-threatening arrhythmias (sustained ventricular tachycardia; ventricular
fibrillation and
cardiopulmonary resuscitation)
* Safety of intracoronary application of autologous bone marrow-derived cells
(t2c001)
(procedural complications, adverse events at 30 days, SAEs at 4 months after
each cell
application)
* Any new malignant disease within 5 years
* Bleeding events within 30 days after intracoronary cell application
Background summary
Patients with symptomatic chronic post-infarction heart failure under full dose
conventional medical
and device treatment including resynchronization therapy frequently suffer from
repeated
rehospitalisations for heart failure, and a high mortality rate. Whereas heart
transplantation may be
considered as option for patients below the age of 65, this alternative is no
possibility for the majority
of elderly patients with symptomatic heart failure. Moreover, heart
transplantation is significantly
limited through the non-availability of donor organs. Thus, the situation is
unsatisfying for the patients
as well as for the treating physicians.
In these patients, the application of bone marrow-derived progenitor cells is a
novel treatment option.
Data of our own non-randomised studies suggest that BM-MNC application reduces
serum levels of
NT-proBNP. In addition, the survival of patients treated with intracoronary
infusion of BM-MNC was
better than the survival predicted by the established SHFM model. This effect
was entirely driven by
patients receiving two sequential intracoronary treatments. However, these data
were obtained from a
non-randomised registry, and, therefore, the current randomized controlled
trial should investigate
whether
- 2 sequential intracoronary BM-MNC applications are associated with a lower
mortality than one
intracoronary BM-MNC application
- 2 intracoronary treatments with BM-MNC are associated with a better survival
than the survival
predicted with the SHFM model.
Study objective
The current randomized controlled trial should investigate
whether
- 2 sequential intracoronary BM-MNC applications are associated with a lower
mortality than one
intracoronary BM-MNC application
- 2 intracoronary treatments with BM-MNC are associated with a better survival
than the survival
predicted with the SHFM model.
Study design
Randomized controlled open-label trial.
Treatment group 1:
Single intracoronary application of autologous bone marrow-derived progenitor
cells (t2c001) into open infarct-related vessel or bypass (n=334)
Treatment group 2:
2 repeated intracoronary applications of autologous bone marrow-derived
progenitor cells (t2c001) into open the same infarct-related vessel or bypass
(n=334), time interval between first and second treatment 4 months
Primary outcome: mortality
Intervention
Treatment group 1:
Single intracoronary application of autologous bone marrow-derived progenitor
cells (t2c001) into open infarct-related vessel or bypass (n=334)
Treatment group 2:
2 repeated intracoronary applications of autologous bone marrow-derived
progenitor cells (t2c001) into open the same infarct-related vessel or bypass
(n=334), time interval between first and second treatment 4 months
Study burden and risks
The patients have the following additional investigations
* One or two cardiac catheterizations with 4 months difference
* One or two bone marrow aspiration(s) under local anaesthesia
* Routine investigations like physical examination and ECG
* 1 transthoracic ultrasound examination of the heart at baseline
* 7 to 8 times blood testing (ca. 30 ml each)
Theodor-Stern-Kai 7
Frankfurt 60590
DE
Theodor-Stern-Kai 7
Frankfurt 60590
DE
Listed location countries
Age
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 and expected to survive > 1 year
• 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), any chronic
inflammatory disease
• 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
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-000595-33-NL |
| CCMO | NL52576.000.15 |