Autologous bone marrow-derived cells for cardioprotection during heart surgery

ISRCTN ISRCTN22639386
DOI https://doi.org/10.1186/ISRCTN22639386
EudraCT/CTIS number 2006-006480-23
Secondary identifying numbers UHL Ref: 10,176
Submission date
01/12/2006
Registration date
14/02/2007
Last edited
19/07/2021
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Circulatory System
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Manuel Galinanes
Scientific

Cardiac Surgery Group
Department of Cardiovascular Sciences
Clinical Science Wing
Glenfield Hospital
Groby Road
Leicester
LE3 9QP
United Kingdom

Phone +44 (0)116 256 3031
Email mg50@le.ac.uk

Study information

Study designRandomised controlled trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Not specified
Study typeTreatment
Scientific titleAutologous bone marrow-derived cells for cardioprotection during heart surgery
Study objectivesThe principal hypothesis that will be tested is that the administration of autologous Bone Marrow Cells (BMCs) during cardiac surgery can reduce myocardial ischaemic injury and improve cardiac function and clinical outcome. This small clinical trial aims to prove the laboratory concept that autologous BMCs protect the heart against myocardial injury caused by ischaemia and serve as a base for a large trial aimed at investigating whether BMCs improve the clinical outcomes and have an impact on the costing of care.

The specific objectives of this project are:
1. To investigate in a randomised, double-blinded study whether the administration of autologous bone marrow cells as an additive to cardioplegia reduces myocardial ischaemic injury during cardiac surgery.
2. To study whether the administration of autologous BMCs improves cardiac function during the early period following cardiac surgery.
Ethics approval(s)Under review at present.
Health condition(s) or problem(s) studiedIschaemic heart disease
InterventionPatients with triple vessel coronary artery disease with or without associated significant disease of the left main stem and undergoing elective CABG surgery will be recruited for the study. Patients will be randomised at the time of surgery to either of the following study groups:

1. Group I: control - receiving serum alone
2. Group II: receiving BMCs at then end of the first dose of cardioplegia and then at the end of each new dose of cardioplegia

Autologous BMCs (diluted in 10 mL of autologous serum) will be administered into the aortic root at the end of cardioplegia infusion (last 20 mL of cardioplegia to ascertain that BMCs remain within the coronary vasculature during the ensuing ischaemic period) or the equivalent amount of serum to act as control. Blood cardioplegia will be used with an initial dose of 1 L and 0.5 L following the completion of each coronary anastomosis, usually every 15 - 20 minutes. Blood samples will be taken before surgery and four, 12, 24 and 48 hours after surgery for determination of plasma levels of troponin I. An Electrocardiogram (ECG) will be recorded before surgery and at four and 24 hours for the identification of new electrical ischaemic changes. A Swan-Ganz catheter will be floated into the pulmonary artery during the induction of anaesthesia for the assessment of cardiac function (cardiac index and stroke volume index) before surgery and 30 minutes, one, two, four, eight, 12, and 24 hours after surgery.

Cardiac filling pressures (central venous pressure between 8 and 12 mmHg and pulmonary capillary wedge pressure between 12 and 16 mmHg with appropriate transfusion), heart rate (between 70 and 90 beats/minute with atrioventricular pacing if required) and systemic vascular resistance index (between 1200 and 1800 units using vasodilators such as Glyceryl Trinitrate [GTN] and vasoconstrictors as vasopressin if required) will be kept within the physiological range. Hospital mortality, the need for inotropic drugs (dopamine more than 10 mg/Kg/min and any other inotropic drug) or intra-aortic balloon pump to support cardiac function and the presence of severe cardiac arrhythmias requiring cardioversion or the use of anti-arrhythmic drugs will be recorded.
Intervention typeOther
Primary outcome measureTroponin I in plasma
Secondary outcome measures1. Left ventricular function
2. Composite clinical outcome
Overall study start date03/01/2007
Completion date03/07/2007

Eligibility

Participant type(s)Patient
Age groupAdult
SexNot Specified
Target number of participants44 (22 in bone marrow group, 22 in control group)
Total final enrolment44
Key inclusion criteria1. Triple vessel coronary artery disease with or without significant disease of the left main stem with indication of elective surgical revascularisation
2. Left ventricular ejection fraction greater than 40%
3. Age 20 to 80 years
Key exclusion criteriaIn addition to not being compliant to the inclusion criteria, the following criteria will be sufficient to exclude patients from entering the study:
1. Cardiogenic shock (need for inotropic drugs, intra-aortic balloon pump)
2. Previous Coronary Artery Bypass Graft (CABG)
3. Percutaneous Coronary Infusion (PCI) in the previous three months
4. History of neoplastic disease
5. History of bleeding disorder
6. Chronic inflammatory disease
7. Active infection
8. Renal impairment (creatinine more than 180 mmol/l)
9. Liver dysfunction (Glutamate Oxalate Transferase [GOT] more than 2 x Upper Limit of Normal [ULN] or International Normalised Ratio [INR] more than 1.5 x ULN)
10. Diabetes
11. Chronic treatment with oral antibiotic agents
Date of first enrolment03/01/2007
Date of final enrolment03/07/2007

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centre

Cardiac Surgery Group
Leicester
LE3 9QP
United Kingdom

Sponsor information

University Hospitals of Leicester NHS Trust (UK)
Hospital/treatment centre

Trust Headquarters
Gwendolen House
Gwendolen Road
Leicester
LE5 4QF
England
United Kingdom

Phone +44 (0)116 258 4199
Email djr8@le.ac.uk
Website http://www.uhl-tr.nhs.uk/about-us/contact-us/uhl-hq
ROR logo "ROR" https://ror.org/02fha3693

Funders

Funder type

Hospital/treatment centre

Cardiac Surgery Group (UK) - a specific group within the University of Leicester and Glenfield Hospital

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Abstract results 01/02/2004 No No
Abstract results 01/11/2006 No No
Results article 26/06/2009 19/07/2021 Yes No

Editorial Notes

19/07/2021: Publication reference, total final enrolment and EudraCT number added.