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Trial registered on ANZCTR


Registration number
ACTRN12610000203055
Ethics application status
Approved
Date submitted
9/03/2010
Date registered
10/03/2010
Date last updated
10/03/2010
Type of registration
Retrospectively registered

Titles & IDs
Public title
Randomized Controlled Study of L-Arginine Blood Cardioplegia Administration in Patients with Reduced Left Ventricular Function Undergoing Coronary Artery Bypass Graft Surgery
Scientific title
Randomized Controlled Study of L-Arginine Blood Cardioplegia and its effects upon cardiac troponin release following Coronary Artery Bypass Graft Surgery in Patients with Reduced Left Ventricular Function
Secondary ID [1] 1473 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ischaemic cardiomyopathy requiring coronary artery surgery 256928 0
Condition category
Condition code
Cardiovascular 257075 257075 0 0
Coronary heart disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients are randomized to receive either blood cardiplegaia, (which is the drug which is used to create myocardial standstill and myocardial protection during cardiac surgery) or to receive blood cardioplegia with teh addition of L-arginine 15 g/l. It is administered directly into the coronary circulation (400 ml) about every 10 -20 mins from the heart lung machine for the duration of aortic cross clamping which averages about 90 min. The heart lung machine is responsible for the function of the heart and the lung while a patient is on cardiopulmonary bypass. It oxygenates the blood and pumps it around the body.
Intervention code [1] 256118 0
Treatment: Drugs
Comparator / control treatment
Standard blood cardioplegia, is a combination of blood and a crystalooid electrolyte solution high in potassium which is used to create myocardial standstill and myocardial protection during cardiac surgery). It is normally administered directly into the coronary circulation (400 ml) from the heart lung machine about every 10 -20 mins for the duration of aortic cross clamping which averages about 90 min.
Control group
Active

Outcomes
Primary outcome [1] 257968 0
Whole blood cardiac troponin I concentration measured by immunoassay, sampled from arterial blood at 15 min, 12 and 24 hr post aortic cross clamp removal
Timepoint [1] 257968 0
15 min, 12 and 24 hrs post aortic cross clamp removal
Secondary outcome [1] 263502 0
1. Markers of myocardial oxidative stress - Coronary sinus concentrations of malondialdehyde, superoxide dismutase, xanthine oxidase
Timepoint [1] 263502 0
5 and 15 min post aortic cross clamp removal
Secondary outcome [2] 263505 0
2. Myocardial lactic acid flux. - this is determined by measuring lactic acid levels by sampling 2 ml of arterial and coronary sinus blood on an ABL 700 series blood gas analyser (Radiometer, Copenhagen, Denmark). Lactate flux is then calculated by subtracting coronary sinus from arterial lactate concentration.
Timepoint [2] 263505 0
1, 5 and 15 min post aortic cross clamp removal
Secondary outcome [3] 263506 0
3. Cardiac function measured by transoesophageal echocardiography
Timepoint [3] 263506 0
Pre and post cardiopulmonary bypass

Eligibility
Key inclusion criteria
Adult male and female patients aged between 18-80 years of age scheduled for elective coronary artery bypass graft surgery requiring cardiopulmonary bypass and with left ventricular ejection fraction less than 30% as determined by preoperative transthoracic or transoesophageal echocardiography
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
patient refusal, renal impairment (creatinine >150 micromol/l), abnormal liver enzymes, allergy to L-arginine, a pre-operative requirement for other than coronary artery surgery, urgent coronary surgery for evolving myocardial infarction or a contraindication to transoesophageal echocardiography

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 256615 0
Other Collaborative groups
Name [1] 256615 0
Australian New Zealand College of Anaesthetists
Address [1] 256615 0
ANZCA House
630 St Kilda Road
Melbourne Vic 3004
Country [1] 256615 0
Australia
Primary sponsor type
Individual
Name
David Andrews
Address
Department of Anaesthesia and Pain Management
The Royal Melbourne Hospital
Grattan Street
Parkville, 3050
Victoria Australia
Country
Australia
Secondary sponsor category [1] 255905 0
None
Name [1] 255905 0
Address [1] 255905 0
Country [1] 255905 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 258645 0
Human Research and Ethics Committee (HREC) The Royal Melbourne Hospital
Ethics committee address [1] 258645 0
Ethics committee country [1] 258645 0
Australia
Date submitted for ethics approval [1] 258645 0
Approval date [1] 258645 0
Ethics approval number [1] 258645 0

Summary
Brief summary
Aim
We aim to detect any significant improvement in myocardial protection when L-arginine is added to standard blood cardioplegia. The study and control populations will consist of patients undergoing coronary artery graft surgery with pre-existing poor myocardial function. This group of individuals often have underlying ischaemia and frequently exhibit low output syndrome (LOS) post-cardiopulmonary bypass. Inadequate myocardial protection resulting in ischaemia-reperfusion injury may be a cause for LOS. As a consequence these patients require a high incidence of pharmacological and mechanical support and frequently experience a protracted stay in the intensive care unit (ICU).
L-arginine has been shown to reduce reperfusion injury when added to cardioplegia. Our hypothesis is that effective prevention of ischaemia-reperfusion injury in the jeopardised myocardium leads to an improvement in myocardial preservation and a reduction in the complications that ensue. To prove this, we propose to conduct a randomised, double blind placebo control trial in which L-arginine is added to standard blood cardioplegia. Markers of reperfusion injury, myocyte damage, will be measured. Other markers will include cardiac function, inotrope use and length of ICU stay.
Study design
A prospective double blind randomised controlled trial of L-arginine cardioplegia administered to patients with known poor myocardial function undergoing coronary artery graft surgery. A minimum of fifty patients in total will be allocated into two groups according to a computer generated random sequence. Once randomization has occurred all participants in the patient’s management will remain blinded to group selection. The control group will receive standard blood cardioplegia technique; while the treatment group will receive L-arginine enriched blood cardioplegia.

Endpoints
1. Indicators of cell death – systemic cardiac Troponin I levels pre-cardiopulmonary bypass at 15 min and 12 and 24hrs post aortic clamp removal. Serum Troponin I levels are a measure of myocardial cell death.
2. Markers of myocardial oxidative stress - coronary sinus concentrations of xanthine oxidase, superoxide dismutase and malondialdehyde pre-cardiopulmonary bypass at 5 and 15 minutes post removal of cross clamp. These are a measure of reperfusion injury.
3. Lactic Acid flux at 1 and 5 and 15 minutes post removal of cross clamp as a measure of myocardial aerobic reserve capacity.
3. Effect upon myocardial function - myocardial systolic and diastolic function as measured by intraoperative transoesophageal echocardiography.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 30908 0
Address 30908 0
Country 30908 0
Phone 30908 0
Fax 30908 0
Email 30908 0
Contact person for public queries
Name 14155 0
Dr David Andrews
Address 14155 0
Department of Anaesthesia and Pain Management
The Royal Melbourne Hospital
Grattan Street
Parkville, 3050
Victoria Australia
Country 14155 0
Australia
Phone 14155 0
+613 9342 7540
Fax 14155 0
Email 14155 0
david.andrews@mh.org.au
Contact person for scientific queries
Name 5083 0
Dr David Andrews
Address 5083 0
Department of Anaesthesia and Pain Management
The Royal Melbourne Hospital
Grattan Street
Parkville, 3050
Victoria Australia
Country 5083 0
Australia
Phone 5083 0
+613 9342 7540
Fax 5083 0
Email 5083 0
david.andrews@mh.org.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary