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Trial registered on ANZCTR

Registration number

ACTRN12621000195853

Ethics application status

Approved

Date submitted

21/12/2020

Date registered

23/02/2021

Date last updated

22/02/2022

Date data sharing statement initially provided

23/02/2021

Type of registration

Prospectively registered

Titles & IDs

Public title

A study to determine the feasibility of a trial investigating the effect of angiotensin II infusion on kidney damage in cardiac surgical patients

Scientific title

Effect of Angiotension-II on Acute Kidney Injury after cardiac surgery - a pilot to determine feasibility of a definitive double blind randomized controlled trial (A-TRAK)

Secondary ID [1]

Nil known

Universal Trial Number (UTN)

U1111-1262-9047

Trial acronym

A-TRAK

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Acute kidney injury

Condition category

Condition code

Anaesthesiology

Other anaesthesiology

Surgery

Other surgery

Cardiovascular

Other cardiovascular diseases

Renal and Urogenital

Kidney disease

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Angiotensin II infusion - dose to maintain mean arterial pressure in range of 70-80mmHg. Dose range 0-40ng/kg/min (titrated to maintain blood pressure in range). Started post-induction of anaesthesia and prior to initiation of cardiopulmonary bypass and continued for 48 hours after conclusion of surgery (as a continuous infusion), or until patient goes to the ward if this occurs sooner. Adherence reviewed by monitoring of electronic record. No other drugs administered as part of the intervention.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Noradrenaline infusion - dose to maintain mean arterial pressure in range of 70-80mmHg. Dose range 0-0.4mcg/kg/min (equivalent vasopressor effect to intervention arm, titrated to maintain blood pressure in range). Started post-induction of anaesthesia and prior to initiation of cardiopulmonary bypass and continued for 48 hours after conclusion of surgery (as a continuous infusion), or until patient goes to the ward if this occurs sooner. Adherence reviewed by monitoring of electronic record. No other drugs administered as part of the control group.

Control group

Active

Outcomes

Primary outcome [1]

Duration of study drug infusion as a percentage of total time. Assessed by patient record and infusion pump review.

Timepoint [1]

Intraoperative and for up to 48 hours postoperative or discharge to ward

Primary outcome [2]

Percentage of patients approached who consent to the study. Assessed by screening log.

Timepoint [2]

Prior to randomisation

Primary outcome [3]

Protocol compliance. Assessed by patient medical record.

Timepoint [3]

At the conclusion of the study

Secondary outcome [1]

Duration of time that mean arterial pressure is in target range (70-80mmHg) as a percentage of total time. As assessed by patient record.

Timepoint [1]

Intraoperative and up to 48 hours postoperative or discharge to ward

Secondary outcome [2]

Adverse events - severe hypertension (mean arterial pressure > 120mmHg with evidence of adverse patient effect, included left ventricular failure or aortic dissection). Assessed using medical record.

Timepoint [2]

Intraoperative and up to 48 hours postoperative or discharge to ward

Secondary outcome [3]

Adverse events - deep venous thrombosis. Assessed using patient medical record

Timepoint [3]

Intraoperative and in first 7 days postoperatively

Secondary outcome [4]

Adrenaline maximum dose . As assessed by patient record.

Timepoint [4]

Intraoperative and up to 48 hours postoperative or discharge to ward

Secondary outcome [5]

Volume of colloid or crystalloid fluid given as assessed by patient record and recorded by clinician

Timepoint [5]

Intraoperative and up to 48 hours postoperative or discharge to ward

Secondary outcome [6]

Largest change in creatinine between most recent immediate preoperative and postoperative (obtained from routine pathology results as documented in medical record)

Timepoint [6]

Between immediate preoperative creatinine and up to 7 days postoperative

Secondary outcome [7]

Creatinine levels (obtained from routine pathology results as documented in medical record)

Timepoint [7]

Day 0 (immediate preoperative), Days 1 and 2 post-operative

Secondary outcome [8]

Sodium (obtained from routine pathology results as documented in medical record)

Timepoint [8]

Day 0 (immediate preoperative), Days 1 and 2 post-operative

Secondary outcome [9]

Renin (additional blood samples taken)

Timepoint [9]

Day 0 (immediate preoperative), Days 1 and 2 post-operative

Secondary outcome [10]

Urinary ACE2 (additional urine samples taken)

Timepoint [10]

Day 0 (immediate preoperative), Days 1 and 2 post-operative

Secondary outcome [11]

Angiotensin I levels (additional blood samples taken)

Timepoint [11]

Day 0 (immediate preoperative), Days 1 and 2 post-operative

Secondary outcome [12]

Creatinine clearance (from 6 hour urine collection)

Timepoint [12]

6 hours of urine output collected between immediate postoperative and 6 hours postoperative

Secondary outcome [13]

Potassium level (obtained from routine pathology results as documented in medical record)

Timepoint [13]

Day 0 (immediate preoperative), Days 1 and 2 post-operative

Secondary outcome [14]

Aldosterone levels (additional blood samples taken)

Timepoint [14]

Day 0 (immediate preoperative), Days 1 and 2 post-operative

Secondary outcome [15]

"Nephrocheck" biomarkers (composite of tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7)) (additional urine samples taken)

Timepoint [15]

Day 0 (immediate preoperative), Days 1 and 2 post-operative

Secondary outcome [16]

Angiotensin II levels (additional blood samples taken)

Timepoint [16]

Day 0 (immediate preoperative), Days 1 and 2 post-operative

Secondary outcome [17]

Adrenaline total dose. As assessed by patient record.

Timepoint [17]

Intraoperative and up to 48 hours postoperative or discharge to ward

Secondary outcome [18]

Milrinone maximum dose. As assessed by patient record.

Timepoint [18]

Intraoperative and up to 48 hours postoperative or discharge to ward

Secondary outcome [19]

Milrinone total dose. As assessed by patient record.

Timepoint [19]

Intraoperative and up to 48 hours postoperative or discharge to ward

Secondary outcome [20]

Noradrenaline maximum dose. As assessed by patient record.

Timepoint [20]

Intraoperative and up to 48 hours postoperative or discharge to ward

Secondary outcome [21]

Noradrenaline total dose. As assessed by patient record.

Timepoint [21]

Intraoperative and up to 48 hours postoperative or discharge to ward

Secondary outcome [22]

Vasopressin maximum dose. As assessed by patient record.

Timepoint [22]

Intraoperative and up to 48 hours postoperative or discharge to ward

Secondary outcome [23]

Vasopressin total dose. As assessed by patient record.

Timepoint [23]

Intraoperative and up to 48 hours postoperative or discharge to ward

Eligibility

Key inclusion criteria

Adult > 18 years old; Cardiac surgery using cardiopulmonary bypass including coronary artery bypass grafting (CABG) surgery, valve surgery, combined CABG/valve surgery; Elevated risk of acute kidney injury (AKI) as predicted by a score >3 on the following scale (ie. 3.5 or greater):
- haemoglobin < 130g/l (2 points), creatinine >100umol/l (2 points), age > 70 (1.5 points), NYHA 4 (1.5 points), BMI > 30 (1.5points)

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

- Major aortic surgery, transplant surgery, pulmonary thrombendarterectomy, ventricular assist device placement
- Already receiving inotropic/vasopressor support
- Dialysis dependent
- Pre-existing uncontrolled hypertension
- Asthma with lung function tests demonstrating reversible airway obstruction or a history of admission to hospital with asthma exacerbations
- Severe LV systolic dysfunction (LVEF <30%)
- Significant pulmonary hypertension (ePSAP > 70mmHg, mPAP > 40mmHg)
- Pregnant or breastfeeding women

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)

Yes, central randomisation by computer, sequence generation will be by an independent researcher not involved in outcome assesssment

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Randomisation by computer, stratified by site

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data

Intervention assignment

Parallel

Other design features

Phase

Phase 3

Type of endpoint/s

Statistical methods / analysis

Pilot study. Sample size determined as 60 by reference to existing literature. Descriptive data will be presented as no. (%), mean (SD), or median (IQR). Exploratory analyses will be done, comparing groups with t-tests (if Normal) or Mann-Whitney U tests, and differences expressed as 95% CI.

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

8/03/2021

Actual

30/03/2021

Date of last participant enrolment

Anticipated

31/12/2021

Actual

17/09/2021

Date of last data collection

Anticipated

31/01/2022

Actual

29/11/2021

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

Austin Health - Austin Hospital - Heidelberg

Recruitment hospital [2]

The Alfred - Melbourne

Recruitment postcode(s) [1]

3084 - Heidelberg

Recruitment postcode(s) [2]

3004 - Melbourne

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

Australian and New Zealand College of Anaesthetists

Address [1]

630 St Kilda Rd, Melbourne, VIC 3004

Country [1]

Australia

Primary sponsor type

Hospital

Name

Austin Health

Address

145 Studley Rd, Heidelberg, VIC 3084

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Austin Health Human Research Ethics Committee

Ethics committee address [1]

Austin Health, 145 Studley Rd, Heidelberg, VIC 3084

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

01/12/2020

Ethics approval number [1]

HREC/68376/Austin-2020

Summary

Brief summary

Each year more than 25,000 Australians have cardiac surgery. While the mortality rate is relatively low (around 1-2%), the rate of problems afterwards such as kidney injury is higher (up to 40%). Acute kidney injury (AKI) is a reduction in kidney function over a short period of time. In many cases it resolves, but patients who have had AKI have higher rates of long-term kidney problems and mortality rates. A few will need dialysis. Maintaining blood flow and pressure for the kidney may help prevent injury. Angiotensin II is produced by the body naturally but can also be given as a drug. It has effects that increase blood pressure. Studies in patients with infection have shown that angiotensin II may improve kidney injury. Animal experiments suggest it may be superior to another drug, known as noradrenaline. Our hypothesis is that angiotensin II may reduce kidney injury. In this pilot study we will determine the feasibility of a definitive study comparing angiotensin II to noradrenaline.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Tim Coulson

Address

Centre for Integrated Critical Care, Department of Medicine & Radiology, Melbourne Medical School, 151 Barry St, The University of Melbourne, Carlton, Victoria 3010

Country

Australia

Phone

+61 3 9035 9662

Fax

[email protected]

Contact person for public queries

Name

Tim Coulson

Address

Centre for Integrated Critical Care, Department of Medicine & Radiology, Melbourne Medical School, 151 Barry St, The University of Melbourne, Carlton, Victoria 3010

Country

Australia

Phone

+61 3 9035 9662

Fax

[email protected]

Contact person for scientific queries

Name

Tim Coulson

Address

Centre for Integrated Critical Care, Department of Medicine & Radiology, Melbourne Medical School, 151 Barry St, The University of Melbourne, Carlton, Victoria 3010

Country

Australia

Phone

+61 3 9035 9662

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

Privacy and data sharing

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

Source	Title	Year of Publication	DOI
Embase	Renin-angiotensin-aldosterone system dynamics after targeted blood pressure control using angiotensin II or norepinephrine in cardiac surgery: mechanistic randomised controlled trial.	2023	https://dx.doi.org/10.1016/j.bja.2023.06.056

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically