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Trial registered on ANZCTR


Registration number
ACTRN12622001040752p
Ethics application status
Not yet submitted
Date submitted
21/07/2022
Date registered
26/07/2022
Date last updated
26/07/2022
Date data sharing statement initially provided
26/07/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
A Pilot, Safety, Feasibility and Efficacy Trial of Hemoperfusion during Continuous Renal Replacement Therapy in Critically Ill Patients with Combined Liver and Kidney Failure
Scientific title
A Pilot, Safety, Feasibility and Efficacy Trial of Hemoperfusion during Continuous Renal Replacement Therapy in Critically Ill Patients with Combined Liver and Kidney Failure
Secondary ID [1] 307631 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Liver failure 327121 0
Kidney failure 327122 0
Condition category
Condition code
Oral and Gastrointestinal 324263 324263 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Renal and Urogenital 324264 324264 0 0
Other renal and urogenital disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Following confirmation of eligibility and randomisation, a member of the investigating team will either add a hemoperfusion cartridge (HA330-II Jafron, Guangdong, China) for 12 hours and then changed to a new cartridge for a total of 2 cartridges over 24 hours of treatment for enrolled participants who receive standard continuous renal replacement therapy therapy in the intensive care unit, followed or preceded (by random allocation) the use of the standard care hemofiltration cartridge without a washout period during continuous renal replacement therapy.
Intervention code [1] 324081 0
Treatment: Devices
Comparator / control treatment
Standard therapy for continuous renal replacement therapy during admission to the intensive care unit.
Control group
Active

Outcomes
Primary outcome [1] 332077 0
Ammonia clearance by the extracorporeal circuit during the 24 hours after commencement of hemoperfusion cartridge therapy during continuous renal replacement therapy.
Timepoint [1] 332077 0
As determined by blood sample analysis of the extracorporeal circuit at time zero (pre-intervention) and at the the end of the 24 hour treatment period of continuous renal replacement therapy as recorded in the participant's medical record.
Secondary outcome [1] 412105 0
Change in serum bilirubin levels over the 24 hour treatment period from the commencement of continuous renal replacement therapy with the hemoperfusion cartridge and during standard continuous renal replacement therapy treatment.
Timepoint [1] 412105 0
As determined by blood sample analysis of the extracorporeal circuit at time zero (pre-intervention) and at the the end of the 24 hour treatment period of continuous renal replacement therapy as recorded in the participant's medical record.
Secondary outcome [2] 412106 0
Change in serum bile acid levels over the 24 hour treatment period from the commencement of continuous renal replacement therapy with the hemoperfusion cartridge and during standard continuous renal replacement therapy treatment.
Timepoint [2] 412106 0
As determined by blood sample analysis of the extracorporeal circuit at time zero (pre-intervention) and at the the end of the 24 hour treatment period of continuous renal replacement therapy as recorded in the participant's medical record.
Secondary outcome [3] 412107 0
Change in ammonia levels over the 24 hour treatment period from the commencement of continuous renal replacement therapy with the hemoperfusion cartridge and during standard continuous renal replacement therapy treatment.
Timepoint [3] 412107 0
As determined by blood sample analysis of the extracorporeal circuit at time zero (pre-intervention) and at the the end of the 24 hour treatment period of continuous renal replacement therapy as recorded in the participant's medical record.
Secondary outcome [4] 412108 0
Change in bile acids levels over the 24 hour treatment period from the commencement of continuous renal replacement therapy with the hemoperfusion cartridge and during standard continuous renal replacement therapy treatment.
Timepoint [4] 412108 0
As determined by blood sample analysis of the extracorporeal circuit at time zero (pre-intervention) and at the the end of the 24 hour treatment period of continuous renal replacement therapy as recorded in the participant's medical record.
Secondary outcome [5] 412109 0
Change in serum bilirubin levels over the 24 hour treatment period from the commencement of continuous renal replacement therapy with the hemoperfusion cartridge and during standard continuous renal replacement therapy treatment.
Timepoint [5] 412109 0
As determined by blood sample analysis of the extracorporeal circuit at time zero (pre-intervention) and at the the end of the 24 hour treatment period of continuous renal replacement therapy as recorded in the participant's medical record.
Secondary outcome [6] 412110 0
Trans-cartridge extraction ratio for serum ammonia between treatment with the hemoperfusion cartridge and during standard continuous renal replacement therapy treatment.
Timepoint [6] 412110 0
As determined by blood sample analysis of the extracorporeal circuit at time zero (pre-intervention) and at the the end of the 24 hour treatment period of both intervention and standard care treatment periods continuous renal replacement therapy as recorded in the participant's medical record.
Secondary outcome [7] 412111 0
Trans-cartridge extraction ratio for serum bilirubin between treatment with the hemoperfusion cartridge and during standard continuous renal replacement therapy treatment.
Timepoint [7] 412111 0
As determined by blood sample analysis of the extracorporeal circuit at time zero (pre-intervention) and at the the end of the 24 hour treatment period of both intervention and standard care treatment periods continuous renal replacement therapy as recorded in the participant's medical record.
Secondary outcome [8] 412153 0
Trans-cartridge extraction ratio for serum bile acids between treatment with the hemoperfusion cartridge and during standard continuous renal replacement therapy treatment
Timepoint [8] 412153 0
As determined by blood sample analysis of the extracorporeal circuit at time zero (pre-intervention) and at the the end of the 24 hour treatment period of both intervention and standard care treatment periods continuous renal replacement therapy as recorded in the participant's medical record.
Secondary outcome [9] 412154 0
Trans-filter extraction ratio for serum ammonia between treatment with the hemoperfusion cartridge and during standard continuous renal replacement therapy treatment.
Timepoint [9] 412154 0
As determined by blood sample analysis of the extracorporeal circuit at time zero (pre-intervention) and at the the end of the 24 hour treatment period of both intervention and standard care treatment periods continuous renal replacement therapy as recorded in the participant's medical record.
Secondary outcome [10] 412155 0
Trans-filter extraction ratio for serum bilirubin between treatment with the hemoperfusion cartridge and during standard continuous renal replacement therapy treatment.
Timepoint [10] 412155 0
As determined by blood sample analysis of the extracorporeal circuit at time zero (pre-intervention) and at the the end of the 24 hour treatment period of both intervention and standard care treatment periods continuous renal replacement therapy as recorded in the participant's medical record.
Secondary outcome [11] 412156 0
Trans-filter extraction ratio for serum bile acids between treatment with the hemoperfusion cartridge and during standard continuous renal replacement therapy treatment.
Timepoint [11] 412156 0
As determined by blood sample analysis of the extracorporeal circuit at time zero (pre-intervention) and at the the end of the 24 hour treatment period of both intervention and standard care treatment periods continuous renal replacement therapy as recorded in the participant's medical record.

Eligibility
Key inclusion criteria
Liver failure and severe acute kidney injury requiring continuous renal replacement therapy
Expected to continue to receive continuous renal replacement therapy for equal to or greater than 48 hours from the time of enrolment
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Suspected or confirmed pregnancy
Do not resuscitate (DNR) order in place
Do not intubate (DNI) order in place
Death is deemed inevitable or imminent during this admission, and either the attending physician, patient or substitute decision-maker is not committed to active treatment
Known human immunodeficiency virus (HIV) infection
Another illness is present that in the investigator’s judgement, will substantially increase the risk associated with the participants participant in the study

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)
Sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Eligible patients will be randomisation via a sealed opaque envelope using block randomisation method stratified by site with variable block sizes will be performed.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Summary statistics will be used to describe the clinical data and presented as median with interquartile range (IQR) or percentages as appropriate. Fisher’s exact test will be used for the comparison of categorical data and the paired Wilcoxon test will be used to compare data between the active treatment group and the control group with statistical significance set a value of <0.05.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
3/10/2022
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 22855 0
Austin Health - Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 38160 0
3084 - Banyule
Recruitment postcode(s) [2] 38159 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 24913 0
France
State/province [1] 24913 0
Bordeaux

Funding & Sponsors
Funding source category [1] 311895 0
Commercial sector/Industry
Name [1] 311895 0
Jafron Biomedical Co, Guangdong, China
Country [1] 311895 0
China
Primary sponsor type
Hospital
Name
Austin Health
Address
Austin Health
145 Studley Road
Heidelberg VIC 3084
Country
Australia
Secondary sponsor category [1] 313375 0
Individual
Name [1] 313375 0
Dr Heidi Gaulke
Address [1] 313375 0
Manager, Office for Research
Austin Hospital
145 Studley Road
Heidelberg VIC 3084
Country [1] 313375 0
Australia

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 311330 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 311330 0
145 Studley Road
Heidelberg VIC 3084
Ethics committee country [1] 311330 0
Australia
Date submitted for ethics approval [1] 311330 0
29/07/2022
Approval date [1] 311330 0
Ethics approval number [1] 311330 0

Summary
Brief summary
We are conducting a pilot, safety, feasibility, efficacy, crossover, open-label randomised controlled trial, of 20 adult critically ill patients, in the Departments of Intensive Care at the Austin Hospital and Bordeaux University Hospital.

Continuous renal replacement therapy (CRRT), an artificial means of providing kidney function support, is often required in acutely ill patients who are admitted to the intensive care unit (ICU).

The aim of CRRT is to achieve adequate blood purification from kidney failure associated toxins (typically non-protein bound small solutes). However, there are additional toxins that are related to liver failure, which should be a target for effective removal but cannot be effectively removed by (e.g. ammonia and/or bilirubin) during the current approach to CRRT. In patients experiencing liver failure that is also complicated by kidney failure, an additional form of blood purification that can be easily added to the CRRT circuit would be desirable.
Such blood purification is now available in the form of hemoperfusion (HP). It consists of a biocompatible coated resin inside a cartridge, which can adsorb large amounts of multiple toxins even when they are protein bound. This new technology has now been used to treat patients with septic shock, COVID-19-related acute respiratory distress syndrome (ARDS) and hyperinflammation as well as the itch associated with end stage kidney disease and advance liver disease. The added form of hemoperfusion offers much promise as a way of detoxifying plasma in acutely ill liver patients admitted to ICU with kidney failure.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 120738 0
Prof Ian Baldwin
Address 120738 0
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg VIC 3084
Country 120738 0
Australia
Phone 120738 0
+61394964835
Fax 120738 0
+61394963932
Email 120738 0
ian.baldwin@austin.org.au
Contact person for public queries
Name 120739 0
Prof Ian Baldwin
Address 120739 0
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg VIC 3084
Country 120739 0
Australia
Phone 120739 0
+61394964835
Fax 120739 0
+61394963932
Email 120739 0
ian.baldwin@austin.org.au
Contact person for scientific queries
Name 120740 0
Prof Ian Baldwin
Address 120740 0
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg VIC 3084
Country 120740 0
Australia
Phone 120740 0
+61394964835
Fax 120740 0
+61394963932
Email 120740 0
ian.baldwin@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?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
16702Study protocol  rinaldo.bellomo@austin.org.au Version 1, dated 25th May 2022; please use the abo... [More Details]



Results publications and other study-related documents

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