To demonstrate that a single intracoronary infusion of autologous bone marrow-derived mononuclear cells in addition to state of the art treatment is safe and reduces allcause mortality in patients with reduced left ventricular ejection fraction (
ID
Source
Brief title
Condition
- Myocardial disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Time from randomisation to all-cause death
Secondary outcome
Secondary efficacy endpoints:
• Time from randomisation to cardiac death
• Time from randomisation to cardiovascular death or
rehospitalisation due to heart failure
• Time from randomisation to cardiovascular
rehospitalisation for:
Recurrent MI
Coronary revascularisation procedures
Heart Failure
Unplanned implantation of ICD/CRT device after the
initial hospitalisation discharge
Stroke
Safety endpoints:
• Incidence of adverse events
• Incidence of bleeding by BARC definitions
• Incidence of syncopes
• Incidence of arrhythmias (A-fib/VT)
• Incidence of neoplastic diseases
Background summary
The long term prognosis of patients suffering from acute myocardial infarction
(AMI) has progressively improved since the introduction of reperfusion
therapies and in particular primary angioplasty. In the setting of ST-elevation
myocardial infarction (STEMI), the immediate reopening of acutely occluded
coronary arteries via primary angioplasty is the treatment of choice to salvage
ischemic myocardium. However, the
sudden re-initiation of blood flow can lead to a local acute inflammatory
response with further endothelial and myocardial damage. This phenomenon,
described as 'reperfusion injury', may explain why, despite optimum myocardial
reperfusion, the short-term mortality after AMI approaches 7% [1] and the
incidence of heart failure approaches 15-20%. Despite the use of full
conventional treatment, including ACE inhibitors, beta-blockers, aldosterone
inhibitors and diuretics, in the context of randomised controlled trials yearly
mortality rates of patients with post-infarction heart failure are still in the
range of 10-13% and rehospitalisation for worsening of heart failure occurs at
a yearly rate of 6-8 %. Registry data indicate a more dismal outcome in real
world clinical experience. A major reason for the high morbidity and mortality
is that the heart has an inadequate regenerative response to the myocardial
necrosis sustained following AMI; cell death from the ischemic damage can lead
to
progressive ventricular dilation and dysfunction through the processes of
adverse left ventricular remodelling.
However, the discovery of tissue resident cardiac stem cells in the mammalian
heart has challenged the long held belief that the heart is a
terminally-differentiated organ and opens up the possibility of using bone
marrow derived stem cells to repair the heart. Indeed, recent experimental
studies documented that bone marrow-derived cell (BMC) injection into the
infarcted heart stimulates the formation of newly formed
cardiac myocytes, although the origin of these myocytes is still a matter of
debate. Numerous pre-clinical studies provided high degree of evidence that
bone marrowderived cells do contribute to cardiac repair after acute myocardial
injury, limit infarct expansion and improve cardiac function most likely via a
paracrine mechanism of action. Pre-clinical evidence is corroborated by several
small to intermediate size clinical trials demonstrating beneficial effects of
bone marrow derived cells on top of the state-of-the-art reperfusion treatment.
Study objective
To demonstrate that a single intracoronary infusion of autologous bone
marrow-derived mononuclear cells in addition to state of the art treatment is
safe and reduces allcause mortality in patients with reduced left ventricular
ejection fraction (<=45%) after successful reperfusion for acute myocardial
infarction when compared to a control group.
Study design
Multinational, multicentre, randomised, open-label, controlled, parallel-group
phase III study.
Group 1: optimal standard of care
Group 2: intracoronary infusion of BM-MNCs 2 to 8 days after successful
reperfusion for acute myocardial infarction
added on top of optimal standard of care.
Patients will be randomised to treatment or control group in a 1:1 ratio.
Randomisation will be stratified according to country.
Intervention
Bone marrow-derived progenitor cells will be obtained from bone marrow.
Intracoronary infusion of BMMNCs will be performed via conventional
percutaneous intracoronary intervention techniques using an over-the-wire
balloon ("low pressure balloon inflation") between 2 to 8 days after initial
acute reperfusion therapy. Patients in the control group will not undergo any
of the described interventions and will not receive the therapy. All patients
will be treated with optimal post myocardial infarction pharmacological
treatment.
Study burden and risks
In previous investigations where the BM-MNC investigational medicinal product
(IMP) manufactured as in the BAMI study has been used (bone marrow-derived
progenitor cells *t2c001*), no BM-MNC associated adverse reactions were
reported.
Aspiration of bone marrow: infection, nerve damage
Hartcatherisation: heart tamponade, hematoma, infection, exposure to radiation
Patients will be tested for HIV, syphilis, hepatitis.
St James' Building, London Chest Hospital, Bonner Road
London E2 9JX
GB
St James' Building, London Chest Hospital, Bonner Road
London E2 9JX
GB
Listed location countries
Age
Inclusion criteria
1. Signed and dated informed consent
2. Men and women of any ethnic origin aged >= 18 years
3. Patients with acute STelevation (including new LBBB)
myocardial infarction as defined by the universal definition of AMI.
4. Successful acute reperfusion therapy (residual stenosis visually <50% and TIMI flow >=2) within 24 hours of symptom
onset or thrombolysis within 12 hours of symptom onset followed by successful percutaneous coronary intervention
(PCI) within 24 hours after thrombolysis
5. Left ventricular ejection fraction <= 45% with significant regional wall motion abnormality assessed by quantitative
echocardiography (central, independent core lab analysis) 3 to 6 days after reperfusion therapy
6. Open coronary artery suitable for cell infusion supplying the target area of abnormal wall motion
Exclusion criteria
1. Participation in another clinical trial within 30 days prior to randomisation
2. Previously received stem/progenitor cell therapy
3. Pregnant or nursing women
4. Mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study or to follow the protocol
5. Necessity to revascularise additional vessels, outside the target coronary artery at the time of BMMNC infusion (additional revascularisations after primary PCI and before BMMNC cell infusion are allowed), unless clinically indicated and according to latest guidelines. This decision should be madfe at the time of the index procedure and explicitly stated at the time.
6. Cardiogenic shock requiring mechanical support
7. Platelet count <100,000/µl, or hemoglobin <8.5 g/dl
8. Impaired renal function, i.e. serum creatinine >2.5 mg/dl
9. Persistent fever or diarrhea not responsive to treatment within 4 weeks prior screening
10. Clinically significant bleeding within 3 months prior screening
11. Uncontrolled hypertension (systolic >180 mmHg and diastolic >120 mmHg)
12. Life expectancy of less than 2 years from any noncardiac
cause or neoplastic disease
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 | EUCTR2012-001495-11-NL |
| CCMO | NL53394.000.15 |