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Trial registered on ANZCTR


Registration number
ACTRN12622000988752p
Ethics application status
Not yet submitted
Date submitted
22/06/2022
Date registered
13/07/2022
Date last updated
13/07/2022
Date data sharing statement initially provided
13/07/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Acute Kidney Injury in patients randomised to the ARISE FLUIDS Randomised Controlled Trial
Scientific title
Sepsis resuscitation and acute kidney injury: a prospective nested cohort study of acute kidney injury in the ARISE FLUIDS Randomised Controlled Trial.
Secondary ID [1] 307416 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record
This study is a sub-study of the ARISE FLUIDS trial NCT04569942

Health condition
Health condition(s) or problem(s) studied:
Acute Kidney Injury 326752 0
Sepsis 326753 0
Condition category
Condition code
Renal and Urogenital 323982 323982 0 0
Kidney disease
Infection 323983 323983 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Observational
Patient registry
True
Target follow-up duration
90
Target follow-up type
Days
Description of intervention(s) / exposure
As part of the ARISE FLUIDS trial (ClinicalTrials.gov Identifier: NCT04569942), patients presenting to the emergency department with presumed septic shock will be randomised to either
1. A ‘restricted fluids and early vasopressor strategy’ whereby ongoing hypotension is managed by a vasopressor infusion titrated to the desired blood pressure, or
2. A ‘larger initial intravenous fluid volume and later introduction of vasopressor strategy’ whereby an additional litre of intravenous fluid will be given for persisting hypotension, and then further, more liberal boluses of fluid as required.

No additional treatment intervention will be imposed by participation in this nested cohort study. Participation in this nested cohort study will involve collection of two urine samples at ARISE FLUIDS enrolment and at 24 hours after enrolment (measured for urinary TIMP-2/IGFBP7 biomarker and markers of urine concentration), and additional data related to renal function from the healthcare record until hospital discharge, censored at 90 days.
Intervention code [1] 323852 0
Not applicable
Comparator / control treatment
Renal outcomes between the patients allocated to each of the ARISE FLUIDS treatment arms will be compared.
Control group
Active

Outcomes
Primary outcome [1] 331782 0
The primary outcome measure will be the most severe KDIGO AKI Stage recorded within 72 hours of enrolment by treatment group. This will be calculated by analysis of urine output and renal function tests (serum creatinine) collected and recorded as part of standard care in the existing healthcare record.
Timepoint [1] 331782 0
72 hours from enrolment into ARISE FLUIDS trial
Secondary outcome [1] 411104 0
Major Adverse Kidney Events (MAKE) defined as death, dialysis dependence or persistently elevated serum creatinine twice patient’s baseline (prior to admission) or estimated baseline. This will be calculated by analysis renal function tests (serum creatinine) collected and recorded as part of standard care, and review of the healthcare record.
Timepoint [1] 411104 0
Hospital discharge
Secondary outcome [2] 411105 0
Severity of AKI (by KIDIGO) among those patients at high risk of AKI at enrolment as indicated by a positive urinary (TIMP-2 and IGFBP7) biomarker
Timepoint [2] 411105 0
72 hours following enrolment in ARISE FLUIDS trial
Secondary outcome [3] 411106 0
Frequency of TIMP-2/IGFBP7 biomarker status changes (from positive to negative, or vice versa) over the resuscitation period. This will be assessed by collection of two specific urine specimens for measurement of the TIMP-2/IGFBP7 biomarker at ARISE FLUIDS randomisation and at 24 hours following randomisation
Timepoint [3] 411106 0
24 hours following enrolment in ARISE FLUIDS trial
Secondary outcome [4] 411107 0
Markers of urine concentration (measured as urine Creatinine, albuminuria, non-albuminuric proteinuria, and osmolality (mOsm/kg)).
Timepoint [4] 411107 0
24 hours following enrolment in ARISE FLUIDS trial
Secondary outcome [5] 411576 0
Major Adverse Kidney Events (MAKE) among those patients at high risk of AKI at enrolment as indicated by a positive urinary (TIMP-2 and IGFBP7) biomarker
Timepoint [5] 411576 0
Hospital discharge
Secondary outcome [6] 411577 0
TIMP-2/IGFBP7 biomarker levels in this population, measured at enrolment and 24 hours. This will be assessed by collection of two specific urine specimens for measurement of the TIMP-2/IGFBP7 biomarker at ARISE FLUIDS randomisation and at 24 hours following randomisation
Timepoint [6] 411577 0
24 hours following enrollment in the ARISE FLUIDS trial

Eligibility
Key inclusion criteria
Eligible for the ARISE FLUIDS RCT. This study's inclusion criteria are as follows:
1. Clinically suspected infection
2. Systolic blood pressure (SBP) <90 mm Hg or mean arterial pressure (MAP) <65 mm Hg, despite a 1000 mLs cumulative total bolus of IV fluid administered over a maximum of 60 minutes; including pre-hospital boluses
3. Arterial or venous blood lactate >2.0 mmol/L
4. At least one dose of an intravenous antimicrobial has been commenced
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Ineligible for the ARISE FLUIDS RCT. This study's exclusion criteria are as follows:
1. Age < 18 years
2. Confirmed or suspected pregnancy
3. Transferred from another acute care facility
4. >2L total IV fluid administered (including prehospital fluids but excluding drugs and flushes)
5. Hypotension suspected to be due to a non-sepsis cause
6. More than 6 hours has elapsed since presentation to the ED or more than 2 hours has elapsed since last Inclusion criterion has been met
7. Treating clinician considers that one or both of the treatment regimens are not suitable for the patient or the study protocol cannot be delivered e.g. limitation of care, requirement for immediate surgery
8. Death is considered imminent or inevitable
9. Underlying disease that makes survival to 90 days is unlikely
10. Inability to follow patient up to day-90 e.g. unstable accommodation, overseas visitor
11. Previously enrolled in ARISE FLUIDS

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
The cohort size has been based on practicalities and funding; no power calculation has been performed. Renal outcomes between treatment groups will be described, with allocation to treatment groups according to the intention to treat principle.
Comparison of clinical outcomes will use multivariable logistic regression, with a propensity score-adjusted analysis as a sensitivity analysis.

Correlation between markers of urinary concentration osmolality (mOsm/kg) and TIMP-2/IGFBP7 biomarker levels will be described using a linear mixed-effects model. A formal statistical analysis plan will be developed prior to collation and analysis of the results.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/09/2022
Actual
Date of last participant enrolment
Anticipated
30/06/2025
Actual
Date of last data collection
Anticipated
30/09/2025
Actual
Sample size
Target
100
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 22603 0
Royal North Shore Hospital - St Leonards
Recruitment postcode(s) [1] 37863 0
2065 - St Leonards

Funding & Sponsors
Funding source category [1] 311692 0
Charities/Societies/Foundations
Name [1] 311692 0
Ramsay Healthcare (Ramsay Research and Teaching Fund Scheme)
Country [1] 311692 0
Australia
Funding source category [2] 311693 0
Charities/Societies/Foundations
Name [2] 311693 0
Intensive Care Foundation
Country [2] 311693 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
The George Institute for Global Health
Address
Level 5 , 1 King St
Newtown
NSW 2042
Country
Australia
Secondary sponsor category [1] 313147 0
Hospital
Name [1] 313147 0
Royal North Shore Hospital
Address [1] 313147 0
1 Reserve Rd
St Leonards
NSW 2065
Country [1] 313147 0
Australia

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 311145 0
Northern Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 311145 0
NSLHD Research Office,
Level 13 Kolling Building, Royal North Shore Hospital,
Reserve Road, St Leonards, NSW, 2065
Ethics committee country [1] 311145 0
Australia
Date submitted for ethics approval [1] 311145 0
27/07/2022
Approval date [1] 311145 0
Ethics approval number [1] 311145 0

Summary
Brief summary
This prospective nested cohort study of Acute Kidney Injury (AKI) in a cohort of patients recruited to the ARISE FLUIDS randomised controlled trrial aims to describe the incidence of AKI with differing strategies of vasopressor use/ fluid resuscitation in patients presenting to the Emergency Department (ED) with septic shock, and to describe the relationship between these resuscitation strategies and sensitive biomarkers of AKI.

As part of the ARISE FLUIDS trial, patients will be randomised to either
1. A ‘restricted fluids and early vasopressor strategy’ whereby ongoing hypotension is managed by a vasopressor infusion titrated to the desired blood pressure, or
2. A ‘larger initial intravenous fluid volume and later introduction of vasopressor strategy’ whereby an additional litre of intravenous fluid will be given for persisting hypotension, and then further, more liberal boluses of fluid as required.

Patients recruited to this nested cohort will have additional granular renal data (creatinine, urine output, etc) collected through the subsequent admission, to determine the incidence and severity of AKI, and important renal outcomes.

In addition, a novel sensitive biomarker (urinary insulin-like growth-factor binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases (TIMP-2) will be measured at enrolment and 24 hours. The relationship between this biomarker, resuscitation strategy, and renal outcomes will be explored.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 120102 0
Dr Lachlan Donaldson
Address 120102 0
Royal North Shore Hospital
Department of Intensive Care Medicine
Reserve Rd, St Leonards
NSW 2065
Country 120102 0
Australia
Phone 120102 0
+61 294632633
Fax 120102 0
Email 120102 0
LDonaldson@georgeinstitute.org.au
Contact person for public queries
Name 120103 0
Dr Lachlan Donaldson
Address 120103 0
Royal North Shore Hospital
Department of Intensive Care Medicine
Reserve Rd, St Leonards
NSW 2065
Country 120103 0
Australia
Phone 120103 0
+61 294632633
Fax 120103 0
Email 120103 0
LDonaldson@georgeinstitute.org.au
Contact person for scientific queries
Name 120104 0
Dr Lachlan Donaldson
Address 120104 0
Royal North Shore Hospital
Department of Intensive Care Medicine
Reserve Rd, St Leonards
NSW 2065
Country 120104 0
Australia
Phone 120104 0
+61 294632633
Fax 120104 0
Email 120104 0
LDonaldson@georgeinstitute.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
This study uses data collected in the course of a larger RCT - Australasian Resuscitation In Sepsis Evaluation: FLUid or Vasopressors In Emergency Department Sepsis (ARISE FLUIDS) (ClinicalTrials.gov Identifier: NCT04569942). Data sharing queries should be addressed to this trials sponsor- Australian and New Zealand Intensive Care Research Centre.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
16445Study protocol  LDonaldson@georgeinstitute.org.au
16446Statistical analysis plan  ldonaldson@georgeinstitute.org.au



Results publications and other study-related documents

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No documents have been uploaded by study researchers.

Documents added automatically
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