Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
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
Date results information initially provided
22/02/2022
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] 303046 0
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 320114 0
Condition category
Condition code
Anaesthesiology 318054 318054 0 0
Other anaesthesiology
Surgery 318325 318325 0 0
Other surgery
Cardiovascular 318326 318326 0 0
Other cardiovascular diseases
Renal and Urogenital 318327 318327 0 0
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] 319333 0
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] 326047 0
Duration of study drug infusion as a percentage of total time. Assessed by patient record and infusion pump review.
Timepoint [1] 326047 0
Intraoperative and for up to 48 hours postoperative or discharge to ward
Primary outcome [2] 326060 0
Percentage of patients approached who consent to the study. Assessed by screening log.
Timepoint [2] 326060 0
Prior to randomisation
Primary outcome [3] 326061 0
Protocol compliance. Assessed by patient medical record.
Timepoint [3] 326061 0
At the conclusion of the study
Secondary outcome [1] 389951 0
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] 389951 0
Intraoperative and up to 48 hours postoperative or discharge to ward
Secondary outcome [2] 389952 0
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] 389952 0
Intraoperative and up to 48 hours postoperative or discharge to ward
Secondary outcome [3] 389953 0
Adverse events - deep venous thrombosis. Assessed using patient medical record
Timepoint [3] 389953 0
Intraoperative and in first 7 days postoperatively
Secondary outcome [4] 389954 0
Adrenaline maximum dose . As assessed by patient record.
Timepoint [4] 389954 0
Intraoperative and up to 48 hours postoperative or discharge to ward
Secondary outcome [5] 389955 0
Volume of colloid or crystalloid fluid given as assessed by patient record and recorded by clinician
Timepoint [5] 389955 0
Intraoperative and up to 48 hours postoperative or discharge to ward
Secondary outcome [6] 389956 0
Largest change in creatinine between most recent immediate preoperative and postoperative (obtained from routine pathology results as documented in medical record)
Timepoint [6] 389956 0
Between immediate preoperative creatinine and up to 7 days postoperative
Secondary outcome [7] 389957 0
Creatinine levels (obtained from routine pathology results as documented in medical record)
Timepoint [7] 389957 0
Day 0 (immediate preoperative), Days 1 and 2 post-operative
Secondary outcome [8] 389958 0
Sodium (obtained from routine pathology results as documented in medical record)
Timepoint [8] 389958 0
Day 0 (immediate preoperative), Days 1 and 2 post-operative
Secondary outcome [9] 389959 0
Renin (additional blood samples taken)
Timepoint [9] 389959 0
Day 0 (immediate preoperative), Days 1 and 2 post-operative
Secondary outcome [10] 389960 0
Urinary ACE2 (additional urine samples taken)
Timepoint [10] 389960 0
Day 0 (immediate preoperative), Days 1 and 2 post-operative
Secondary outcome [11] 389961 0
Angiotensin I levels (additional blood samples taken)
Timepoint [11] 389961 0
Day 0 (immediate preoperative), Days 1 and 2 post-operative
Secondary outcome [12] 389962 0
Creatinine clearance (from 6 hour urine collection)
Timepoint [12] 389962 0
6 hours of urine output collected between immediate postoperative and 6 hours postoperative
Secondary outcome [13] 389967 0
Potassium level (obtained from routine pathology results as documented in medical record)
Timepoint [13] 389967 0
Day 0 (immediate preoperative), Days 1 and 2 post-operative
Secondary outcome [14] 389968 0
Aldosterone levels (additional blood samples taken)
Timepoint [14] 389968 0
Day 0 (immediate preoperative), Days 1 and 2 post-operative
Secondary outcome [15] 389969 0
"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] 389969 0
Day 0 (immediate preoperative), Days 1 and 2 post-operative
Secondary outcome [16] 390947 0
Angiotensin II levels (additional blood samples taken)
Timepoint [16] 390947 0
Day 0 (immediate preoperative), Days 1 and 2 post-operative
Secondary outcome [17] 390948 0
Adrenaline total dose. As assessed by patient record.
Timepoint [17] 390948 0
Intraoperative and up to 48 hours postoperative or discharge to ward
Secondary outcome [18] 390949 0
Milrinone maximum dose. As assessed by patient record.
Timepoint [18] 390949 0
Intraoperative and up to 48 hours postoperative or discharge to ward
Secondary outcome [19] 390950 0
Milrinone total dose. As assessed by patient record.
Timepoint [19] 390950 0
Intraoperative and up to 48 hours postoperative or discharge to ward
Secondary outcome [20] 390951 0
Noradrenaline maximum dose. As assessed by patient record.
Timepoint [20] 390951 0
Intraoperative and up to 48 hours postoperative or discharge to ward
Secondary outcome [21] 390952 0
Noradrenaline total dose. As assessed by patient record.
Timepoint [21] 390952 0
Intraoperative and up to 48 hours postoperative or discharge to ward
Secondary outcome [22] 390953 0
Vasopressin maximum dose. As assessed by patient record.
Timepoint [22] 390953 0
Intraoperative and up to 48 hours postoperative or discharge to ward
Secondary outcome [23] 390954 0
Vasopressin total dose. As assessed by patient record.
Timepoint [23] 390954 0
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?
No
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
60
Accrual to date
Final
60
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 18237 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [2] 18238 0
The Alfred - Melbourne
Recruitment postcode(s) [1] 32301 0
3084 - Heidelberg
Recruitment postcode(s) [2] 32302 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 307456 0
Charities/Societies/Foundations
Name [1] 307456 0
Australian and New Zealand College of Anaesthetists
Country [1] 307456 0
Australia
Primary sponsor type
Hospital
Name
Austin Health
Address
145 Studley Rd, Heidelberg, VIC 3084
Country
Australia
Secondary sponsor category [1] 308129 0
None
Name [1] 308129 0
Address [1] 308129 0
Country [1] 308129 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307534 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 307534 0
Austin Health, 145 Studley Rd, Heidelberg, VIC 3084
Ethics committee country [1] 307534 0
Australia
Date submitted for ethics approval [1] 307534 0
Approval date [1] 307534 0
01/12/2020
Ethics approval number [1] 307534 0
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 107578 0
Dr Tim Coulson
Address 107578 0
Centre for Integrated Critical Care, Department of Medicine & Radiology, Melbourne Medical School, 151 Barry St, The University of Melbourne, Carlton, Victoria 3010
Country 107578 0
Australia
Phone 107578 0
+61 3 9035 9662
Fax 107578 0
Email 107578 0
[email protected]
Contact person for public queries
Name 107579 0
Dr Tim Coulson
Address 107579 0
Centre for Integrated Critical Care, Department of Medicine & Radiology, Melbourne Medical School, 151 Barry St, The University of Melbourne, Carlton, Victoria 3010
Country 107579 0
Australia
Phone 107579 0
+61 3 9035 9662
Fax 107579 0
Email 107579 0
[email protected]
Contact person for scientific queries
Name 107580 0
Dr Tim Coulson
Address 107580 0
Centre for Integrated Critical Care, Department of Medicine & Radiology, Melbourne Medical School, 151 Barry St, The University of Melbourne, Carlton, Victoria 3010
Country 107580 0
Australia
Phone 107580 0
+61 3 9035 9662
Fax 107580 0
Email 107580 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
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
SourceTitleYear of PublicationDOI
EmbaseRenin-angiotensin-aldosterone system dynamics after targeted blood pressure control using angiotensin II or norepinephrine in cardiac surgery: mechanistic randomised controlled trial.2023https://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.