Contact information
Type
Scientific
Primary contact
Prof Manuel Galinanes
ORCID ID
Contact details
Cardiac Surgery Group
Department of Cardiovascular Sciences
Clinical Science Wing
Glenfield Hospital
Groby Road
Leicester
LE3 9QP
United Kingdom
+44 (0)116 256 3031
mg50@le.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
UHL Ref: 10,176
Study information
Scientific title
Acronym
Study hypothesis
The 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
Under review at present.
Study design
Randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Condition
Ischaemic heart disease
Intervention
Patients 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 type
Other
Phase
Not Specified
Drug names
Primary outcome measures
Troponin I in plasma
Secondary outcome measures
1. Left ventricular function
2. Composite clinical outcome
Overall trial start date
03/01/2007
Overall trial end date
03/07/2007
Reason abandoned
Eligibility
Participant inclusion criteria
1. 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
Participant type
Patient
Age group
Adult
Gender
Not Specified
Target number of participants
44 (22 in bone marrow group, 22 in control group)
Participant exclusion criteria
In 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
Recruitment start date
03/01/2007
Recruitment end date
03/07/2007
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Cardiac Surgery Group
Leicester
LE3 9QP
United Kingdom
Sponsor information
Organisation
University Hospitals of Leicester NHS Trust (UK)
Sponsor details
Trust Headquarters
Gwendolen House
Gwendolen Road
Leicester
LE5 4QF
United Kingdom
+44 (0)116 258 4199
djr8@le.ac.uk
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Hospital/treatment centre
Funder name
Cardiac Surgery Group (UK) - a specific group within the University of Leicester and Glenfield Hospital
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15040600
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17059931
Publication citations
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Galiñanes M, Loubani M, Davies J, Chin D, Pasi J, Bell PR, Autotransplantation of unmanipulated bone marrow into scarred myocardium is safe and enhances cardiac function in humans., Cell Transplant, 2004, 13, 1, 7-13.
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Kubal C, Sheth K, Nadal-Ginard B, Galiñanes M, Bone marrow cells have a potent anti-ischemic effect against myocardial cell death in humans., J. Thorac. Cardiovasc. Surg., 2006, 132, 5, 1112-1118, doi: 10.1016/j.jtcvs.2006.06.028.