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Trial registered on ANZCTR


Registration number
ACTRN12624001068550
Ethics application status
Approved
Date submitted
19/08/2024
Date registered
3/09/2024
Date last updated
22/09/2024
Date data sharing statement initially provided
3/09/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
A Pilot, Two-Centre, Open-Label, Safety and Physiological Efficacy Randomised Controlled Trial of Intravenous Amino Acid Therapy in Vasopressor-Dependent Adults Admitted to the Intensive Care Unit
Scientific title
A Pilot, Two-Centre, Open-Label, Safety and Physiological Efficacy Randomised Controlled Trial of Intravenous Amino Acid Therapy in Vasopressor-Dependent Adults Admitted to the Intensive Care Unit
Secondary ID [1] 312501 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Critical illness 334379 0
Condition category
Condition code
Cardiovascular 331017 331017 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Synthamin-17 without electrolytes will be administered as a single continuous Intravenous infusion for 36 hours at a dose of 2 g/kg/day of ideal body weight (to a maximum of 100 g/day) that will be commenced and only given while the participant is in the intensive care unit. Adherence will be monitored via electronic medical record review. The composition of Synthamin-17 10% without electrolytes is:
- The excipients are sodium metabisulfite, acetic acid and water for injection.
- Essential amino acids: Leucine 7.30 g, Phenylalanine 5.60 g, Methionine 4.00 g, Lysine (as the hydrochloride salt) 5.80 g, Isoleucine 6.00 g, Valine 5.80 g, Histidine 4.80 g, Threonine 4.20 g, Tryptophan 1.80 g.
- Non-essential amino acids: Alanine 20.7 g, Glycine 10.3 g, Arginine 11.5 g, Proline 6.80 g, Tyrosine 400 mg, Serine 5.00 g.
Intervention code [1] 329028 0
Treatment: Other
Comparator / control treatment
Compound Sodium Lactate (Hartmann's solution) for 36 hours at a rate that is associated with the delivery of 2g/kg/ideal body weight/day (to a maximum of 100g/day.
Control group
Active

Outcomes
Primary outcome [1] 338782 0
The difference between baseline creatinine clearance and creatinine clearance at 36 hours after initiation of the study infusion between patients receiving amino acid vs a balanced crystalloid infusion
Timepoint [1] 338782 0
Baseline (pre-initiation) and at 36 hours after initiation of the study infusion.
Secondary outcome [1] 437410 0
Cumulative urine output in millilitres over 36 hours after initiation of the study infusion
Timepoint [1] 437410 0
Total volume of urine at 36 hours after initiation of the study infusion
Secondary outcome [2] 437435 0
Serum creatinine at 36 hours after initiation of the study infusion
Timepoint [2] 437435 0
Baseline (pre-initiation) and at 36 hours after initiation of the study infusion
Secondary outcome [3] 437436 0
Plasma cystatin C at 36 hours after initiation of the study infusion
Timepoint [3] 437436 0
Baseline (pre-initiation) and at 36 hours after initiation of the study infusion
Secondary outcome [4] 437437 0
Urinary neutrophil gelatinase-associated lipocalin (NGAL)
Timepoint [4] 437437 0
Baseline (pre-initiation) and at 36 hours after initiation of the study infusion
Secondary outcome [5] 437438 0
Urine albumin/creatinine ratio at 36 hours after initiation of the study infusion
Timepoint [5] 437438 0
Baseline (pre-initiation) and at 36 hours after initiation of the study infusion
Secondary outcome [6] 437439 0
Urinary electrolytes at 36 hours after initiation of the study infusion
Timepoint [6] 437439 0
Baseline (pre-initiation) and at 36 hours after initiation of the study infusion
Secondary outcome [7] 437440 0
Maximum severity of acute kidney injury up to day 7 (defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria)
Timepoint [7] 437440 0
7 days after enrolment
Secondary outcome [8] 437441 0
Duration of acute kidney injury up to day 30
Timepoint [8] 437441 0
30 days after enrolment
Secondary outcome [9] 437442 0
Occurrence of acute kidney disease (AKD) (defined by the Acute Dialysis Quality Initiative – ADQI criteria)
Timepoint [9] 437442 0
Hospital discharge
Secondary outcome [10] 437443 0
Need for renal replacement therapy (RRT) up to day 30
Timepoint [10] 437443 0
30 days after enrolment
Secondary outcome [11] 437444 0
Days alive and renal replacement therapy-free to day 30
Timepoint [11] 437444 0
30 days after enrolment
Secondary outcome [12] 437445 0
Days alive and AKI free to day 7
Timepoint [12] 437445 0
7 days after enrolment.
Secondary outcome [13] 437446 0
Days alive and AKD free to day 30
Timepoint [13] 437446 0
30 days after enrolment
Secondary outcome [14] 437447 0
ICU length of stay in days
Timepoint [14] 437447 0
ICU discharge
Secondary outcome [15] 437448 0
Hospital length of stay in days
Timepoint [15] 437448 0
Hospital discharge
Secondary outcome [16] 437449 0
Days alive and ICU free to day 30
Timepoint [16] 437449 0
30 days after enrolment
Secondary outcome [17] 437450 0
Days alive and ICU free to day 30
Timepoint [17] 437450 0
30 days after enrolment
Secondary outcome [18] 437451 0
ICU mortality
Timepoint [18] 437451 0
ICU discharge
Secondary outcome [19] 437452 0
Hospital mortality
Timepoint [19] 437452 0
Hospital discharge

Eligibility
Key inclusion criteria
Adult aged equal to or greater than 18 years
Admitted to the intensive care unit for less than 72 hours
Receiving vasopressor therapy and expected to continue for 24 hours
The patient is expected to remain in ICU for greater than 24 hours
Appropriate intravascular device, such as a central line or peripherally inserted central catheter, to administer the intervention
Appropriate devices to collect samples; arterial line and indwelling urinary catheter
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Severe Acute kidney injury, as defined by Kidney Disease Improving Global Outcomes (KDIGO) stage 3 criteria
Requirement for renal replacement thearapy, such as dialysable toxin
Urea greater than 30 mmol/L
Absence of a central access device
Already of vasopressor therapy for greater than 24 hours
Pre-admission chronic kidney disease with an estimated glomerular filtration rate of less than of less than 30 ml/min
Acute estimated glomerular filtration rate of less than 30 ml/min
Chronic haemodialysis or peritoneal dialysis
Need for extracorporeal membrane oxygenation
Previous enrolment in this study
Pregnant or lactating
Patients who are not to receive full active treatment
Transferred from another intensive care unit

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)
A centralised, web-based system (REDCap) will be employed, allowing 24-hour enrolment and random allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The random allocation sequence will be generated using a computer software program and embedded into the REDCap system. Site investigators, site research coordinators, and study participants will not have access to the allocation sequence.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
A statistician will perform data analysis on an intention-to-treat basis. Summary statistics will describe the clinical data and be presented as mean ± SD, median with interquartile range (IQR) or percentages as appropriate. Chi-squared analysis with Fisher’s exact test (when appropriate), and Student’s t-test (Mann Whitney U test for non-normal distributions) or mixed linear models for repeated measurements will be used to compare data between the active treatment group and the control group with statistical significance declared for probability values of 0.05 or less. The outcome of excluded patients (e.g., due to other trials) will be analysed per the CONSORT guidelines. A complete and finalised statistical analysis plan will be prepared and made available before the recruitment.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/10/2024
Actual
Date of last participant enrolment
Anticipated
31/10/2025
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
60
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 26775 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [2] 26776 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 42826 0
3084 - Heidelberg
Recruitment postcode(s) [2] 42827 0
4102 - Woolloongabba

Funding & Sponsors
Funding source category [1] 316923 0
Hospital
Name [1] 316923 0
Austin Hospital
Country [1] 316923 0
Australia
Primary sponsor type
Hospital
Name
Austin Hospital
Address
Country
Australia
Secondary sponsor category [1] 319177 0
Individual
Name [1] 319177 0
Professor Rinaldo Bellomo
Address [1] 319177 0
Country [1] 319177 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315677 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 315677 0
https://www.austin.org.au/Office-for-Research/
Ethics committee country [1] 315677 0
Australia
Date submitted for ethics approval [1] 315677 0
22/07/2024
Approval date [1] 315677 0
19/09/2024
Ethics approval number [1] 315677 0

Summary
Brief summary
Acute kidney injury is common in critically ill patients, especially in those requiring vasopressor therapy. We hypothesize that an intravenous infusion of amino acids in such patients will increase glomerular function without tubular injury when compared to a balanced crystalloid solution of equal volume. In this two-centre, pilot safety and efficacy randomised controlled trial we plan to enrol 60 adult patients with the study drug delivered via infusion while the participant is in the intensive care unit.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 135474 0
Prof Rinaldo Bellomo
Address 135474 0
Department of Intensive Care, Austin Hospital, 145 Studley Road, Heidelberg, Victoria, Australia 3084
Country 135474 0
Australia
Phone 135474 0
+61 394965992
Fax 135474 0
Email 135474 0
[email protected]
Contact person for public queries
Name 135475 0
Rinaldo Bellomo
Address 135475 0
Department of Intensive Care, Austin Hospital, 145 Studley Road, Heidelberg, Victoria, Australia 3084
Country 135475 0
Australia
Phone 135475 0
+61 394965992
Fax 135475 0
Email 135475 0
[email protected]
Contact person for scientific queries
Name 135476 0
Rinaldo Bellomo
Address 135476 0
Department of Intensive Care, Austin Hospital, 145 Studley Road, Heidelberg, Victoria, Australia 3084
Country 135476 0
Australia
Phone 135476 0
+61 394965992
Fax 135476 0
Email 135476 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
Ethics approval not sought for sharing of patient data


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.