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Trial registered on ANZCTR


Registration number
ACTRN12620000514909p
Ethics application status
Submitted, not yet approved
Date submitted
28/01/2020
Date registered
27/04/2020
Date last updated
27/04/2020
Date data sharing statement initially provided
27/04/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Haemofiltration with OXiris: Multicentre Evaluation in Acute Kidney Injury (HOME-AKI). A pilot study comparing two devices used for renal replacement therapy in the intensive care unit in patients with acute kidney injury related to sepsis.
Scientific title
A pilot multicentre open-label randomised controlled trial during treatment for acute kidney injury in critically ill patients with septic shock comparing two haemofilter membrane devices, the AN69ST and the newly available oXiris haemofiltration membrane for early resolution of shock as well as other clinical and technical performance outcomes.
Secondary ID [1] 300372 0
None
Universal Trial Number (UTN)
U1111-1247-3435
Trial acronym
HOME-AKI
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Kidney Injury 315992 0
Sepsis 315993 0
Septic Shock 315994 0
Condition category
Condition code
Infection 314265 314265 0 0
Studies of infection and infectious agents
Renal and Urogenital 314266 314266 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention is continuous renal replacement (CRRT) with the newly available oXiris haemofiltration membrane (ARTG ID 302001). The intervention is an approved device which is used in place of another approved device as part of usual care for acute kidney injury requiring renal replacement therapy. All intervention is provided in intensive care units (ICUs) by registered nurses with postgraduate qualifications in intensive care nursing. The intervention is provided individually and is required a variable number of times over a variable period (for example a median number of 3 haemofilter devices would be used over a period of 1 to 7 days). Renal replacement practices vary depending on the treating clinicians goals for therapy. This is unaffected by the intervention itself and the decision to commence CRRT is independent of the research study. Intervention adherence will be monitored by research staff at participating centres.
Intervention code [1] 316655 0
Treatment: Devices
Comparator / control treatment
The research control is the current standard AN69ST (acryl nitrite 69 surface treated, ARTG ID 195199) haemofiltration membrane. This is the device that has been in use for many years for continuous renal replacement therapy (CRRT) in intensive care units (ICUs). The control is an approved device which is used as part of usual care for acute kidney injury requiring renal replacement therapy. All control device therapy is provided in intensive care units (ICUs) by registered nurses with postgraduate qualifications in intensive care nursing. The control device use is provided individually and is required a variable number of times over a variable period (for example a median number of 3 haemofilter devices would be used over a period of 1 to 7 days). Renal replacement practices vary depending on the treating clinicians goals for therapy. This is unaffected by the choice of device itself.
Control group
Active

Outcomes
Primary outcome [1] 322657 0
A composite outcome of time alive and vasopressor free at 7 days (in hours) assessed by review of clinical records during the first 7 days following commencement of continuous renal replacement therapy.
Timepoint [1] 322657 0
7 days post time of first commencement of continuous renal replacement therapy (168 hours).
Secondary outcome [1] 379191 0
Median circuit life (hours) extracted from the renal replacement therapy device electronic logs.
Timepoint [1] 379191 0
End of renal replacement therapy with assigned device (variable).
Secondary outcome [2] 379192 0
Mortality - assessed by review of medical records and follow up calls at 28 and 90 days post randomisation.
Timepoint [2] 379192 0
7, 28 and 90 days post commencement of first continuous renal replacement therapy.
Secondary outcome [3] 379193 0
Cumulative vasopressor requirements, assessed by review of medical records during intensive care admission.
Timepoint [3] 379193 0
During continuous renal replacement therapy (variable).
Secondary outcome [4] 379194 0
Vasopressor requirements, assessed by review of medical records.
Timepoint [4] 379194 0
4, 12 and 24 hours post first commencement of continuous renal replacement therapy.
Secondary outcome [5] 379195 0
Cumulative fluid requirements, assessed by review of medical records.
Timepoint [5] 379195 0
4, 12 and 24 hours post first commencement of continuous renal replacement therapy.
Secondary outcome [6] 379196 0
Change in sequential organ failure assessment (SOFA) score.
Timepoint [6] 379196 0
24 and 48 hours post first commencement of renal replacement therapy.
Secondary outcome [7] 379197 0
Duration of requirement of renal replacement therapy assessed by review of medical records.
Timepoint [7] 379197 0
During hospital admission (variable)
Secondary outcome [8] 379198 0
Duration of requirement of renal replacement therapy assessed by review of medical records and follow up calls.
Timepoint [8] 379198 0
90 days post randomisation
Secondary outcome [9] 379199 0
Renal replacement therapy requirement assessed by review of medical records and follow up calls.
Timepoint [9] 379199 0
28 and 90 days post randomisation
Secondary outcome [10] 379200 0
Change in C-reactive protein where measured as part of usual care by review of medical records.
Timepoint [10] 379200 0
7 days post commencement of continuous renal replacement therapy.
Secondary outcome [11] 379201 0
Analysis of circuit haemodynamic profiles, as recorded within the continuous renal replacement therapy device memory card storage.
Timepoint [11] 379201 0
Variable, maximum 90 days post first commencement of continuous renal replacement therapy.
Secondary outcome [12] 379202 0
Cytokine levels within a subgroup cohort of patients, assessed by blood sampling via existing vascular access devices.
Timepoint [12] 379202 0
Time 0, 4-6 and 20-24 hours post first commencement of continuous renal replacement therapy.
Secondary outcome [13] 379203 0
Subgroup patient blood beta lactam antibiotic levels
Timepoint [13] 379203 0
Time 0, 4-6 and 20-24 hours post first commencement of continuous renal replacement therapy.
Secondary outcome [14] 379204 0
Subgroup blood and effluent metabolic and proteomic profiles. These profiles are descriptive and this is a composite outcome assessed using serum mass spectrometry.
Timepoint [14] 379204 0
Time 0, 4-6 hours and 20-24 hours post first commencement of continuous renal replacement therapy.
Secondary outcome [15] 381874 0
Change in white blood cell count where measured as part of usual care by review of medical records.
Timepoint [15] 381874 0
7 days post commencement of continuous renal replacement therapy.

Eligibility
Key inclusion criteria
Inclusion Criteria (must have 1 + 2 +3)
1. Sepsis, as defined by:
1.1. Suspected or documented infection AND
1.2. An acute increase of greater than 2 SOFA points consequent to the infection (indicating organ dysfunction)
2. Septic shock, as defined by:
2.1. Sepsis and need for vasopressor therapy to keep mean arterial pressure (MAP) greater than or equal to 65 mmHg for greater than or equal to 2 hours
2.2. Lactate greater than 2 mmol/L after volume resuscitation at any time in the preceding 24 hours
3. Acute kidney injury with the requirement for CRRT to control one or more of:
3.1. Volume status/fluid overload
3.2. Hyperkalaemia
3.3. Metabolic acidosis
3.4. Uraemia
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Known chronic kidney disease stage 5 (eGFR < 15 mL/min/1.73m2) or on established renal replacement therapy (peritoneal or intermittent haemodialysis)
• Previous renal replacement therapy on this hospital admission
• Known heparin sensitivity (e.g. heparin induced thrombocytopaenia, HIT)
• Anticipated concurrent use of extracorporeal membrane oxygenation (ECMO)
• Age <18 years
• Pregnancy

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)
Allocation is concealed - randomisation table is generated in statistical software (Stata) prior to trial commencement and trial group is assigned by electronic system (REDCap).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
An electronic randomization schedule will be created in SAS (SAS Institute, NC, USA) and uploaded to the trial REDCap (Harris et al, J Biomed Inform. 2009 Apr;42(2):377–81) database to deliver (with suitable reserve options) the expected overall sample size of N = 150. The randomized allocation to oXiris or usual care (AN69ST) will have an overall 1:1 ratio constructed from blocks of variable size, and the schedule will also be stratified by site (hospital). A clinical staff member with knowledge of the patient’s details will access a secure Web page for the electronic randomization process.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Data including patient demographics, and assay results will be summarized according to their type and according to treatment group and overall. Binary data will be presented as proportions with 95% confidence intervals. Continuous data will be presented as means (standard deviation, SD) if approximately normally distributed and as median (interquartile range, IQR) and full range [range] otherwise. Log or other variance-stabilizing transformations may be employed as appropriate.
The primary outcome will be assessed between randomized groups using an unpaired t test initially, and subsequently within a multivariable linear model accounting for relevant covariables.
Binary outcomes will be presented initially as univariable risk ratios and /or odds ratios with 95% CI as appropriate, with subsequent assessment within generalized linear models using similar covariates to the above multivariable linear models.
Exploratory analysis of metabolomic and proteomic profiles will be undertaken using random forest analysis in a nested cohort of 40 patients (at a single site - The Royal Melbourne Hospital). This analysis is to be performed at a single site for consistency and logistic reasons. Specific metabolites and protein quantities will be compared using t-tests.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
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)
VIC
Recruitment hospital [1] 15695 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [2] 15696 0
The Alfred - Melbourne
Recruitment hospital [3] 15697 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [4] 15698 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [5] 15699 0
Dandenong Hospital - Dandenong
Recruitment hospital [6] 15700 0
Ballarat Health Services (Base Hospital) - Ballarat Central
Recruitment postcode(s) [1] 29115 0
3050 - Parkville
Recruitment postcode(s) [2] 29116 0
3004 - Melbourne
Recruitment postcode(s) [3] 29117 0
3084 - Heidelberg
Recruitment postcode(s) [4] 29118 0
3168 - Clayton
Recruitment postcode(s) [5] 29119 0
3175 - Dandenong
Recruitment postcode(s) [6] 29120 0
3350 - Ballarat Central

Funding & Sponsors
Funding source category [1] 304797 0
Commercial sector/Industry
Name [1] 304797 0
Baxter Healthcare Corporation
Address [1] 304797 0
One Baxter Parkway, Deerfield, Illinois 60015, U.S.A
Country [1] 304797 0
United States of America
Primary sponsor type
Hospital
Name
Melbourne Health
Address
Department of Research
CITY CAMPUS
Level 2
South West
300 Grattan Street
Parkville Victoria
Country
Australia
Secondary sponsor category [1] 305120 0
None
Name [1] 305120 0
Address [1] 305120 0
Country [1] 305120 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 305212 0
Melbourne Health Human Research Ethics Committee
Ethics committee address [1] 305212 0
Melbourne Health Human Research Ethics Committee
The Royal Melbourne Hospital,
300 Grattan Street,
Parkville 3050,
Victoria
Ethics committee country [1] 305212 0
Australia
Date submitted for ethics approval [1] 305212 0
29/01/2020
Approval date [1] 305212 0
Ethics approval number [1] 305212 0

Summary
Brief summary
Sepsis and other inflammatory syndromes commonly result in acute kidney Injury requiring renal replacement therapy (RRT) in intensive care and this is associated with high patient mortality. Failure of the RRT circuit leads to lack of treatment time, blood loss and increased costs (both financial and care giver time).
The oXiris membrane is a recent development in haemofilter membrane technology that advances on the membrane currently in use. It is treated to allow increased adsorption of endotoxin (produced by bacteria and contributing to the sepsis process) and cytokines associated with septic shock and the membrane is heparin-bonded which may reduce the risk of circuit failure.
The oXiris membrane is easily integrated with existing clinical care and this multicentre randomised controlled trial will identify if it has a physiological effect on the shock state or requirement of vasoactive support, as well as any impact on treatment adequacy (by increasing circuit life). Additionally, there is the prospect of new information about possible effects on the proteins and metabolites produced in septic shock during RRT, providing an opportunity for detection of future biomarkers or treatment targets.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 99626 0
Dr Benjamin Sansom
Address 99626 0
ICU Administration Offices,
Level 5, B Building
300 Grattan Street,
Parkville, VIC
3050
Country 99626 0
Australia
Phone 99626 0
+61 3 9342 9234
Fax 99626 0
Email 99626 0
benjamin.sansom@mh.org.au
Contact person for public queries
Name 99627 0
Dr Benjamin Sansom
Address 99627 0
ICU Administration Offices,
Level 5, B Building
300 Grattan Street,
Parkville, VIC
3050
Country 99627 0
Australia
Phone 99627 0
+61 3 9342 9234
Fax 99627 0
Email 99627 0
benjamin.sansom@mh.org.au
Contact person for scientific queries
Name 99628 0
Dr Benjamin Sansom
Address 99628 0
ICU Administration Offices,
Level 5, B Building
300 Grattan Street,
Parkville, VIC
3050
Country 99628 0
Australia
Phone 99628 0
+61 3 9342 9234
Fax 99628 0
Email 99628 0
benjamin.sansom@mh.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-indentified patient data will be stored locally and available on request. Release of such data would be on a case by case basis and only that underlying published results will be initially considered for release.
When will data be available (start and end dates)?
Data will be available at completion of study (July 2022) and for a minimum of 7 years after publication.
Available to whom?
Availability will be on a case by case basis to any established researcher who has submitted any reasonable proposal for access. Availability will be agreed by corporate supporter prior to agreement.
Available for what types of analyses?
Raw data will be made available to qualifying researchers for the achievement of aims of initial proposal.
How or where can data be obtained?
By contacting the principal investigator via email availability of data will be arranged. Intellectual property remains that of the corporate supporter as per established agreements. The principal investigator can be contacted via email: benjamin.sansom@mh.org.au
What supporting documents are/will be available?
No other documents available
Summary results
No Results