Randomised controlled trial to compare the effects of granulocyte-colony stimulating factor (G-CSF) and autologous bone marrow progenitor cells infusion on quality of life and left ventricular function in patients with heart failure secondary to ischaemic heart disease

ISRCTN ISRCTN68837678
DOI https://doi.org/10.1186/ISRCTN68837678
Protocol serial number 1.2
Sponsor Barts and the London NHS Trust (UK)
Funder The Heart Cells Foundation
Submission date
28/07/2005
Registration date
23/11/2005
Last edited
04/03/2013
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Circulatory System
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Anthony Mathur
Scientific

The London Chest Hospital
Bonner Road
London
E2 9JX
United Kingdom

+44 (0)208 983 2216
a.mathur@qmul.ac.uk

Study information

Primary study designInterventional
Study designRandomised controlled trial
Secondary study designRandomised controlled trial
Scientific title
Study acronymREGENERATE-IHD
Study objectives1. Administration of G-CSF to patients with heart failure secondary to ischaemic heart disease will lead to an increase in circulating progenitor cells as measured by peripheral CD34+ positive cell counts
2. Cardiac function and symptoms will improve in patients in whom the peripheral CD34+ counts increase in response to G-CSF administration
3. Direct coronary injection of autologous bone marrow derived stem cells will confer an additional improvement in cardiac function and symptoms above that derived from G-CSF infusion alone
4. Direct intramyocardial injection of autologous bone marrow derived stem cells will lead to an improvement in cardiac function and symptoms above that derived from G-CSF infusion alone
Ethics approval(s)Not provided at time of registration
Health condition(s) or problem(s) studiedHeart failure secondary to ischaemic heart disease.
InterventionDaily subcutaneous injections of G-CSF at 10 µg/kg or placebo OR daily subcutaneous injections of G-CSF at 10 µg/kg followed by intracoronary injection of stem cells or placebo OR daily subcutaneous injections of G-CSF at 10 µg/kg followed by intramyocardial injection of stem cells or placebo
Intervention typeOther
Primary outcome measure(s)

At 6 months:
1. The change in global left ventricular ejection fraction (LVEF) at 6 months relative to baseline measured by quantitative left ventriculography
2. The change in regional wall motion score index at 6 months relative to baseline measured by tissue doppler imaging
3. The change in quality of life scores compared to baseline

Key secondary outcome measure(s)

At 6 months:
1. Death as result of the underlying cardiac condition
2. The occurence of major arrhythmias defined as ventricular tachycardia or survived sudden death
3. Presence of clinically evident heart failure
4. The change in global left ventricular ejection fraction at 6 months relative to baseline measured by resting echocardiography
4. The change in global and regional wall motion score index measured by resting echocardiography
5. Serum levels of amino-terminal pro-brain natriuretic peptide (NT-BNP)
6. Change in myocardial function as measured by magnetic resonance imaging (MRI) scanning (first 40 suitable patients in each group)
7. Change in voltage and shortening maps as assessed by NOGA (intramyocardial group only)

At 12 months:
1. The occurrence of a major adverse cardiac event (MACE)
2. The change in left ventricular ejection fraction relative to baseline measured by resting echocardiography using Simpson's rule
3. The change in global and regional wall motion score index measured by resting echocardiography and tissue doppler imaging
4. Change in quality of life scores
5. Serum levels of amino-terminal pro-brain natriuretic peptide (NT-BNP)
5. Change in myocardial function as measured by MRI scanning (first 40 suitable patients in each group)

Completion date18/05/2010

Eligibility

Participant type(s)Patient
Age groupAdult
SexAll
Target sample size at registration300
Key inclusion criteriaPatients with a diagnosis of heart failure secondary to ischaemic heart disease attending a heart failure clinic for optimisation of their heart failure medication or who are on optimal heart failure treatment under supervision from their physician.
Key exclusion criteria1. Recent acute coronary sydrome as judged by a rise of troponin above normal values in the last 6 months
2. The presence of cardiogenic shock
3. The presence of acute left and/or right-sided pump failure as judged by the presence of pulmonary oedema and/or new peripheral oedema
4. Known severe pre-existent left ventricular dysfunction (ejection fraction <10% prior to randomisation)
5. Congenital cardiac disease
6. Cardiomyopathy secondary to a reversible cause e.g. thyroid disease, alcohol abuse, hypophosphataemia, hypocalcaemia, cocaine abuse, selenium toxicity and chronic uncontrolled tachycardia
7. Cardiomyopathy in association with a neuromuscular disorder e.g. Duchenne's progressive muscular dystrophy
8. Contra-indication for bone marrow aspiration
9. Known active infection
10. Known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV)
11. Lifestyle with high risk for infection with HIV, HBV, or HCV
12. Chronic inflammatory disease
13. Serious known concomitant disease with a life expectancy of less than one year
14. Follow-up impossible (no fixed abode etc.)
15. Previous participation in this study
16. Female subjects of childbearing potential
17. Paced rhythm >80% of the time
18. Serum creatinine >200 mg/dl
Date of first enrolment18/05/2005
Date of final enrolment18/05/2010

Locations

Countries of recruitment

  • United Kingdom
  • England

Study participating centre

The London Chest Hospital
London
E2 9JX
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Interim results article interim results 01/01/2009 Yes No
BMC - Part of Springer Nature Springer Nature