ANZCTR - Registration

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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]

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

Condition category

Condition code

Cardiovascular

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]

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]

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]

15 min, 12 and 24 hrs post aortic cross clamp removal

Secondary outcome [1]

1. Markers of myocardial oxidative stress - Coronary sinus concentrations of malondialdehyde, superoxide dismutase, xanthine oxidase

Timepoint [1]

5 and 15 min post aortic cross clamp removal

Secondary outcome [2]

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]

1, 5 and 15 min post aortic cross clamp removal

Secondary outcome [3]

3. Cardiac function measured by transoesophageal echocardiography

Timepoint [3]

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

Sex

Both males and females

Can healthy volunteers participate?

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

1/09/2005

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]

Other Collaborative groups

Name [1]

Australian New Zealand College of Anaesthetists

Address [1]

ANZCA House
630 St Kilda Road
Melbourne Vic 3004

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Human Research and Ethics Committee (HREC) The Royal Melbourne Hospital

Ethics committee address [1]

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

Ethics approval number [1]

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

Address

Country

Phone

Fax

Contact person for public queries

Name

Dr David Andrews

Address

Department of Anaesthesia and Pain Management
The Royal Melbourne Hospital
Grattan Street
Parkville, 3050
Victoria Australia

Country

Australia

Phone

+613 9342 7540

Fax

david.andrews@mh.org.au

Contact person for scientific queries

Name

Dr David Andrews

Address

Department of Anaesthesia and Pain Management
The Royal Melbourne Hospital
Grattan Street
Parkville, 3050
Victoria Australia

Country

Australia

Phone

+613 9342 7540

Fax

david.andrews@mh.org.au

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

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