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Trial registered on ANZCTR


Registration number
ACTRN12619000788178
Ethics application status
Approved
Date submitted
15/05/2019
Date registered
28/05/2019
Date last updated
28/05/2019
Date data sharing statement initially provided
28/05/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
comparing circuit life between modified membrane and standard membrane in liver failure patients
Scientific title
Comparing Circuit Life between Modified AN69ST Membrane vs. Standard Membrane Dialyser In Liver Failure Patients with Severe Acute Kidney Injury Study
Secondary ID [1] 298253 0
Nil known
Universal Trial Number (UTN)
Trial acronym
The MODIFY Trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
critical illness 312853 0
liver failure 312854 0
severe acute kidney injury 312855 0
Condition category
Condition code
Renal and Urogenital 311353 311353 0 0
Kidney disease
Oral and Gastrointestinal 311426 311426 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Liver failure patients with severe acute kidney injury (AKI) admitted in ICU at the Austin Hospital and treated with continuous renal replacement therapy(CRRT) will be randomly allocated in a 1:1 ratio to receive either modified AN69ST membrane (oXiris®) or standard CRRT membrane. After the first filter has clotted, the second filter will be introduced and will be the one not used for the first treatment. After these two filters have been used, the study will be ceased in that patient. However, if the patient continues to require CRRT, they will continue to receive such treatment with a standard CRRT membrane as is usual care. There is no wash-out period between two filters. An approximate duration for the time study per patient is 2 days
All other aspects of RRT will follow ICU protocols prescribed by intensivist. The protocols include: blood flow of 200 ml/min for CVVHDF, Prismaflex machine, effluent flow rate of 2000 ml/hr, removal of fluid as needed according to clinical needs. we will audit of nurse notes and CRRT prescription order to assess fidelity.

Intervention code [1] 314497 0
Treatment: Devices
Comparator / control treatment
This is a cross-over, open-labelled study in liver failure patients with severe AKI treated with CRRT. After randomized and received either modified AN69ST membrane (oXiris®) or standard CRRT membrane for first filter and the first dialyser is discontinued, patient will alternate to use the other dialysis membrane
- If a patient is started with modified AN69ST membrane dialyzer (oXiris®). The patient will be switched to use standard membrane dialyser for a second dialyser.
- If a patient is started with standard membrane dialyser. The patient will be switched to use modified AN69ST membrane dialyser (oXiris®) for a second dialyser.
After both of dialysers are discontinued, the study will be ceased in that patient
All other aspects of RRT will be the same during period of both filters prescribed by intensivist. The protocols include: blood flow of 200 ml/min for CVVHDF, Prismaflex machine, effluent flow rate of 2000 ml/hr, removal of fluid as needed according to clinical needs.
Control group
Active

Outcomes
Primary outcome [1] 320085 0
Extracorporeal circuit lifespan

The primary outcome is documented by progressive cumulative hours of operation for each filter between modified AN69ST membrane (oXiris®) and standard membrane which is calculated from the start of a CRRT session until non-elective circuit disconnection due to filter clotting or transmembrane pressure (TMP) > 300 mm Hg
Timepoint [1] 320085 0
Study will be ceased if two consecutive sessions of dialysis membrane are applied:
1. Heparin-coated membrane dialyzer (oXiris®) AND
2. Standard membrane dialyzer
Secondary outcome [1] 370476 0
Inflammatory cytokine levels: interleukin-6 (IL-6)

serum will be stored at -80°C and then will be sent to The Florey Research Institute for measure the level of IL-6 by ELISA method.
Timepoint [1] 370476 0
measured cytokine level at time 0, 6 and 12 hours after start CRRT
Secondary outcome [2] 370697 0
Inflammatory cytokine levels: interleukin-8 (IL-8)
serum will be stored at -80°C and then will be sent to The Florey Research Institute for measure the level of IL-8 by ELISA method.
Timepoint [2] 370697 0
measured cytokine level at time 0, 6 and 12 hours after start CRRT
Secondary outcome [3] 370698 0
Inflammatory cytokine levels: Interleukin (IL-10)
serum will be stored at -80°C and then will be sent to The Florey Research Institute for measure the level of IL-10 by ELISA method.
Timepoint [3] 370698 0
measured cytokine level at 0, 6 and 12 hours after start CRRT

Eligibility
Key inclusion criteria
1. Patients have liver failure and severe AKI requiring CRRT AND
2. Patients have contraindications for regional citrate anticoagulant
3. Patients have contraindications for systemic heparin
4. Patient who, in the judgment of the treating clinician, are expected to continue CRRT greater than or equal to 48 h
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patient age is < 18 years
2. Pregnancy
3. DNR (do not resuscitate) DNI (do not intubate) orders
4. Death is deemed imminent or inevitable during this admission, and either the attending physician, patient or substitute decision-maker is not committed to active treatment
5. Patient needs to receive systemic anticoagulation for other indications

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 not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
we believe that a study of 30 patients would provide sufficient exposure to the study protocol (each patient is treated with both of one circuit of standard membrane dialyser and modified AN69ST membrane dialyzer leading to total 60 dialysis membrane are used)
Summary statistics will be used to describe the clinical data and presented as mean ± SD, median with interquartile range (IQR) or percentages as appropriate. Chi-squared analysis with Fisher’s exact test (when appropriate), and paired Student’s t-test (Wilcoxon test for non-normal distributions) 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.

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] 13761 0
Austin Health - Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 26510 0
3084 - Heidelberg

Funding & Sponsors
Funding source category [1] 302793 0
Hospital
Name [1] 302793 0
Austin Hospital
Address [1] 302793 0
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg VIC 3084
Country [1] 302793 0
Australia
Primary sponsor type
Hospital
Name
Austin Hospital
Address
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg VIC 3084
Country
Australia
Secondary sponsor category [1] 302741 0
Individual
Name [1] 302741 0
Professor Rinaldo Bellomo
Address [1] 302741 0
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg VIC 3084
Country [1] 302741 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303384 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 303384 0
Austin Health
145 Studley Road
Heidelberg VIC 3084
Ethics committee country [1] 303384 0
Australia
Date submitted for ethics approval [1] 303384 0
13/02/2019
Approval date [1] 303384 0
14/05/2019
Ethics approval number [1] 303384 0
HREC/51672/Austin-2019

Summary
Brief summary
In patients who have both liver and kidney failure, average circuit life of continuous renal replacement therapy (CRRT) is approximately half compared to other group of patients receiving CRRT due to circuit clotting. However, liver failure patients can’t receive anticoagulants to prevent circuit clotting because of high risk for developed toxicity and bleeding. Modified membrane (oXiris®) is coated with anti-clotting material and has ability to remove cytokine in blood. This study is a pilot, single-center, prospective, randomized, crossover, open-label, clinical controlled trial which aim to assess the efficacy of modified membrane (oXiris®) compared to standard membrane and we hypothesized that modified membrane (oXiris®) has ability to prolong CRRT circuit life compared to standard membrane dialyser and decrease the blood level of cytokines.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 93486 0
Prof Rinaldo Bellomo
Address 93486 0
Department of Intensive Care Austin Hospital 145 Studley Road Heidelberg
Vic 3084
Country 93486 0
Australia
Phone 93486 0
+61 3 9496 5992
Fax 93486 0
+61 3 9496 5992
Email 93486 0
rinaldo.bellomo@austin.org.au
Contact person for public queries
Name 93487 0
Dr Glenn Eastwood
Address 93487 0
Department of Intensive Care Austin Hospital 145 Studley Road Heidelberg
Vic 3084
Country 93487 0
Australia
Phone 93487 0
+61 3 9496 4835
Fax 93487 0
+61 3 9496 3932
Email 93487 0
glenn.eastwood@austin.org.au
Contact person for scientific queries
Name 93488 0
Prof Rinaldo Bellomo
Address 93488 0
Department of Intensive Care Austin Hospital 145 Studley Road Heidelberg
Vic 3084
Country 93488 0
Australia
Phone 93488 0
+61 3 9496 5992
Fax 93488 0
+61 3 9496 5992
Email 93488 0
rinaldo.bellomo@austin.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
What supporting documents are/will be available?
No other documents available
Summary results
No Results