Condition category
Circulatory System
Date applied
01/12/2006
Date assigned
14/02/2007
Last edited
04/10/2007
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

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

http://www.uhl-tr.nhs.uk/about-us/contact-us/uhl-hq

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

  1. 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.

  2. 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.

Additional files

Editorial Notes