The idea behind this study is to show that stem cell therapy is not just effective and safe but also an accessible, feasible and economically sound therapeutic option for patients with IHD and severe heart failureThe present aim is to perform at…
ID
Source
Brief title
Condition
- Heart failures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is change in left ventricle end-systolic volume (LVESV) at
6 months follow-up between CSCC_ASC and placebo treated measured by
echocardiography.
Secondary outcome
The secondary endpoints are safety evaluated by development of allogeneic
antibodies and laboratory safety measurements 1, 3, 6 and 12 months after
treatment and changes in left ventricular ejection fraction (LVEF),
end-diastolic volume and myocardial mass at 6 months follow-up. The changes in
left ventricle function will be measured by echocardiography (ECHO) or computed
tomography (CT). LVESV is a widely used measure of the functional status of the
left ventricle and is superior to LVEF for prediction of survival in patients
with LVEF below 50%. Other secondary endpoints are changes in NYHA, CCS, Kansas
City Cardiomyopathy Questionnaire, Seattle Angina Questionnaire, 6 min walking
test, additional echocardiographic measures (Global strain %, left atrium
volume, e*, s*) and NT-pro-BNP. In addition, safety of allogeneic CSCC_ASCs
with respect to incidence and severity of serious adverse events and suspected
unrelated serious adverse events will be evaluated at 12 months follow-up. A
combined endpoint of
1. death, hospitalization for worsening heart failure including inserting of a
bi-ventricular pacemaker, hospitalization because of ventricular tachycardia or
fibrillation 1, 2 and 3 years after treatment
2. death, hospitalization for any cardiovascular reason, hospitalization for
worsening heart failure including inserting of a bi-ventricular pacemaker,
hospitalization because of ventricular tachycardia or fibrillation 1, 2 and 3
years after treatment.
Background summary
Ischemic heart disease (IHD) caused by coronary artery disease is the most
common cause of death with more than 17 million deaths worldwide each year and
a major cause of hospital admissions in industrialized countries. ((World
Health Organization, 2011)
It is an increasing economic health problem due to increasing morbidity in an
ageing population. Classical therapies have reduced mortality of IHD
significantly, but left an increasing number of patients with chronic IHD
and/or heart failure without further treatment options.
Thus, there is an unmet need for novel, effective treatments for chronic IHD
and heart failure to improve patient*s survival and quality of life and reduce
health care costs. Stem cell therapy is emerging as a viable therapeutic option
in this patient group as well as in several debilitating diseases for which no
cure is currently available.
To implement and disseminate a new clinical therapy with stem cells to all
potential candidates, safety and efficacy has to go hand-in-hand with
feasibility, - it has to be logistically easy to request and perform the
treatment. There are however many logistical obstacles in the present used
clinical models for stem cell therapies within cardiology.
At the moment, most frequently autologous stem cells are used for the treatment
of patients with ischemic heart disease. Yet the properties and proliferation
rate of the obtained cells differ considerably from patient to patient.
Therefore, it is difficult to treat patients with a standardized number of
cells in the clinical studies. Moreover, it is logistically difficult to
schedule the treatment procedure due to large variations in cell production
time.
The Advanced Therapy Medicinal Product (ATMP) regulation has increased
considerably within the last years. Presently, only few hospitals within the
European Union have cell culture facilities approved for ATMP production.
Combined with the use of autologous treatment this leads to administratively,
logistical and cost extensive transportation issues.
The project proposes a new stem cell treatment concept (intra-myocardial
injections of allogeneic adipose derived stem cells (ASCs) manufactured in
concordance with ATMP regulations), which is logistically easy to implement in
clinical practice by elimination of the many hurdles identified during
production of autologous stem cell medicinal products and conduction of
clinical trials, e.g. the manual handling of cell production, transportation
back and forth of tissues and cells, mismatch between readiness of the cell
product and the patient*s clinical condition, availability of patients, trained
personal and catheterization facilities.
We expect that intra-myocardial injection of allogeneic adipose derived stem
cells (ASCs), will increase quality of life and survival for patients with
chronic IHD and/or heart failure end reduces health care costs.
The SCIENCE project aims at allogeneic ASC therapy as an established and
approved hospital standard care for patients with severe heart failure due to
coronary artery disease. The project builds on proven safety and efficacy of
mesenchymal stromal cell therapy in clinical phase I and II trials with
patients with coronary heart disease and heart failure performed by members of
the consortium (Friis 2011, Haack-Sørensen 2013, Mathiasen 2012, 2013, Qayyum
2012, Tendera 2009, Gyöngyösi 2009, Vrtovec 2013, 2013, Heeger 2012).
The idea behind this study is also to show that stem cell therapy is not just
effective and safe but also an accessible, feasible and economically sound
therapeutic option for patients with IHD and severe heart failure.
Study objective
The idea behind this study is to show that stem cell therapy is not just
effective and safe but also an accessible, feasible and economically sound
therapeutic option for patients with IHD and severe heart failure
The present aim is to perform at clinical double-blind placebo-controlled
CSCC_ASC multicentre study in heart failure patients in Europe to investigate
the regenerative capacity of the CSCC_ASC treatment.
The overall aim is to establish the relevant clinical documentation of the
regenerative capacity of CSCC_ASC treatment in patients with heart failure from
two supplementary clinical trials which then can be forwarded to the European
Medicines Agency for a final approval of allogeneic CSCC_ASC therapy as
standard care therapy in patients with ischemic heart failure in European
Countries.
Study design
Patients will be randomized (2:1) to either CSCC_ASC or placebo (saline).
Treatment group:
NOGA mapping guided injection of 100 million allogeneic adipose derived stem
cells (CSCC_ASC) with MYOSTAR injection catheter
Control group:
NOGA mapping guided injection of placebo (saline) with MYOSTAR injection
catheter
Intervention
Treatment group:
NOGA mapping guided injection of 100 million allogeneic adipose derived stem
cells (CSCC_ASC) with MYOSTAR injection catheter
Control group:
NOGA mapping guided injection of placebo (saline) with MYOSTAR injection
catheter
Study burden and risks
Burden:
Patients have the following additional investigations:
5 transthoraric ultrasound examination of the heart
2 CT and/or MRI of the heart
5 NYHA and CCS classification
5 Kansas City Cardiomyopathy Questionnaire, Seattle Angina Questionnaire and
EQ-5d Questionnaire
Routine investigations like physical examination and ECG
8 times bloodtesting (ca 20 mL each)
5 times 6 min walktest,
5 times registration of serious adverse events en suspected unrelated serious
adverse events
1 NOGA mapping guided injection of allogeneic adipose derived stem cells
(CSCC_ASC)/placebo with MYOSTAR injection catheter
Risk:
Based on conducted clinical trials with allogeneic mesenchymal stem cells and
ASCs it is not expected that there will be any side-effects to the use of the
allogeneic CSCC_ASC product.
Other risks to the patient are associated with the procedures performed
(mentioned above) and are considered low.
Blegdamsvej 9
Copenhagen 2100
DK
Blegdamsvej 9
Copenhagen 2100
DK
Listed location countries
Age
Inclusion criteria
Inclusion criteria:
1. 30 to 80 years of age
2. Signed informed consent
3. Chronic stable ischemic heart disease
4. Symptomatic Heart failure (NYHA II-III)
5. LVEF <=45% on echocardiography, CT or MRI scan.
6. Plasma NT-pro-BNP > 300 pg/ml (> 35 pmol/L)
7. Maximal tolerable heart failure medication
8. Medication unchanged two months prior to inclusion/signature of informed
consent. Changes in diuretics accepted.
9. No option for percutaneous coronary intervention (PCI) or coronary artery
bypass graft (CABG)
10. Patients who have had PCI or CABG within six months of inclusion
must have a new angiography less than one month before inclusion or at
least four months after the intervention to rule out early restenosis
11. Patients cannot be included until three months after implantation of
a cardiac resynchronisation therapy device (CRTD) and 1 month after an ICD unit
Exclusion criteria
Exclusion criteria
1. Heart Failure (NYHA I or IV)
2. Acute coronary syndrome with elevation of CKMB or troponins, stroke or
transitory cerebral ischemia within six weeks of inclusion. Constant elevated
troponin due to renal failure, heart failure etc. do not exclude the patient.
3. Other revascularisation treatment within four months of treatment
4. If clinically indicated the patient should have a coronary angiography
before inclusion
5. Moderate to severe aortic stenosis (valve area < 1.3 cm2) or
valvular disease with option for surgery or interventional therapy.
6. Aortic valve replacement with an artificial heart valve. However, a
trans-septal treatment approach can be considered in these patients.
7. If the patient is expected to be candidate for MitraClip therapy of mitral
regurgitation in the 12 months follow-up period.
8.. Diminished functional capacity for other reasons such as: obstructive
pulmonary disease (COPD) with forced expiratory volume (FEV) <1
L/min, moderate to severe claudication or morbid obesity
9. Clinical significant anaemia (haemoglobin < 6 mmol/L), leukopenia
(leucocytes < 2 109/L), leucocytosis (leucocytes >14 109/L) or
thrombocytopenia (thrombocytes < 50 109/L)
10. Reduced kidney function (eGFR < 30 ml/min)
11. Left ventricular thrombus
12. Anticoagulation treatment that cannot be paused during cell injections.
Patients can continue with platelet inhibitor treatment
13. Patients with reduced immune response
14. History with malignant disease within five years of inclusion or
suspected malignity - except treated skin cancer other than melanoma
15. Pregnant women
16. Other experimental treatment within four weeks of baseline tests
17. Participation in another intervention trial
18. Life expectancy less than one year
19. Known hypersensitivity to DMSO, penicillin and streptomycin
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 | EUCTR2015-002929-19-NL |
| CCMO | NL54174.000.15 |