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Trial registered on ANZCTR


Registration number
ACTRN12618000168257
Ethics application status
Approved
Date submitted
10/01/2018
Date registered
2/02/2018
Date last updated
2/02/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Monitoring vascular endothelial function by microdialysis in septic patients.
Scientific title
Monitoring endothelial function of children with sepsis in the paediatric intensive care unit
Secondary ID [1] 293757 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Sepsis and septic shock 306140 0
critical illness 306141 0
Condition category
Condition code
Infection 305254 305254 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental patients will undergo the insertion of a microdialysis catheter to monitor interstitial protein levels and serial blood tests for biomarkers of inflammation (cytokines) and endothelial activation.

A 66 Linear Microdialysis Catheter (AshMed Medical Pty Ltd) will be inserted under the skin of the forearm in anaesthetised children by the research personnel under the supervision of the anaesthetist. The microdialysis catheter will be perfused with sterile saline (0.9% NaCl) solution. The microdialysis pump will run at 1 microliter per minute.

Dialysate samples will be collected every 2 ± 2 hours in 0.5 mL Eppendorf tubes. The tubes will be placed on ice and transferred to the laboratory. The microdialysate will be analysed for protein and inflammatory markers.

Second hourly urine samples from the indwelling urinary catheter will be collected throughout the procedure and for the first 48 post-operative hours.
As per the paediatric intensive care unit (PICU) protocol, all patients will have routine post-operative blood taken for blood gas analysis (including lactate and central venous oxygen saturations), full blood count, plasma electrolytes, renal and liver functions tests and coagulation profiles. At this time researchers will organise the collection of an additional 1.0-2.0mL of blood. In this sample 200 µL of plasma will be used to measure levels of EphA2 (Human Magnetic Luminex® Screening Assay kit, R&D Systems, Inc.), EphA4, EphB4, ephrin-A1 and ephrin-B2 (ELISA, R&D Systems Inc.). We will also measure inflammatory markers (CRP, procalcitonin), complement (C5a), endothelial markers (endocans, VEGF, Ang-1, Ang-2) and cytokines (TNF-a, IL-1ß, IL-6, IL-8, IL-10 and IFN-gamma) using standard Bio-RAD ELISA kits as per the manufacturers’ instructions.

The catheter will remain in situ for the duration of the study - experimental patients 72 hours, control patients until discharge from the recovery ward.

If the catheter is accidentally dislodged the researchers will decide if the catheter should be replaced.

Intervention code [1] 300009 0
Diagnosis / Prognosis
Comparator / control treatment
The control patients are children undergoing an elective surgical procedure under general anaesthesia. The children will undergo the insertion of a microdialysis catheter to monitor interstitial protein levels and serial blood tests for biomarkers of inflammation (cytokines) and endothelial activation.


A 66 Linear Microdialysis Catheter (AshMed Medical Pty Ltd) will be inserted under the skin of the forearm in anaesthetised children by the research personnel under the supervision of the anaesthetist. The microdialysis catheter will be perfused with sterile saline (0.9% NaCl) solution. The microdialysis pump will run at 1 microliter per minute.

Dialysate samples will be collected every 2 ± 2 hours in 0.5 mL Eppendorf tubes. The tubes will be placed on ice and transferred to the laboratory. The microdialysate will be analysed for protein and inflammatory markers.

Second hourly urine samples from the indwelling urinary catheter will be collected throughout the procedure and for the first 48 post-operative hours.

As per the paediatric intensive care unit (PICU) protocol, all patients will have routine post-operative blood taken for blood gas analysis (including lactate and central venous oxygen saturations), full blood count, plasma electrolytes, renal and liver functions tests and coagulation profiles. At this time researchers will organise the collection of an additional 1.0-2.0mL of blood. In this sample 200 µL of plasma will be used to measure levels of EphA2 (Human Magnetic Luminex® Screening Assay kit, R&D Systems, Inc.), EphA4, EphB4, ephrin-A1 and ephrin-B2 (ELISA, R&D Systems Inc.). We will also measure inflammatory markers (CRP, procalcitonin), complement (C5a), endothelial markers (endocans, VEGF, Ang-1, Ang-2) and cytokines (TNF-a, IL-1ß, IL-6, IL-8, IL-10 and IFN-gamma) using standard Bio-RAD ELISA kits as per the manufacturers’ instructions.

The catheter will remain in situ for the duration of the study - experimental patients 72 hours, control patients until discharge from the recovery ward.

If the catheter is accidentally dislodged the researchers will decide if the catheter should be replaced.
Control group
Active

Outcomes
Primary outcome [1] 304407 0
Monitoring interstitial protein levels (vascular leak) by quantiating microdialysate protein levels and plasma biomarkers of inflammation and endothelial activation. (composite primary outcome)

From the routine blood samples, 200 µL of plasma will be used to measure levels of EphA2 (Human Magnetic Luminex® Screening Assay kit, R&D Systems, Inc.), EphA4, EphB4, ephrin-A1 and ephrin-B2 (ELISA, R&D Systems Inc.). We will also measure plasma inflammatory markers (CRP, procalcitonin), complement (C5a), endothelial markers (endocans, VEGF, Ang-1, Ang-2) and cytokines (TNF-a, IL-1ß, IL-6, IL-8, IL-10 and IFN-gamma) using standard Bio-RAD ELISA kits as per the manufacturers’ instructions.
Timepoint [1] 304407 0
post-admission to PICU - 0h (admission), 1h, 2h, 4h, 12h, 24h, 48h, 72h - we have not identified a primary timepoint but the most useful data will be in the first 2-12h post-admission to PICU.
Secondary outcome [1] 341858 0
Urine from the indwelling catheter will be collected and urinary proteins measured (microalbuminuria) by standard laboratory techniques (Pierce protein assay).
Timepoint [1] 341858 0
post-admission to PICU - 0h (admission), 1h, 2h, 4h, 12h, 24h, 48h, 72h

Eligibility
Key inclusion criteria
1. control - children (n=20) undergoing elective surgery under general anaesthesia.

2. experimental - children (n=100) admitted to the paediatric intensive care unit with a diagnosis of sepsis or septic shock.
Minimum age
No limit
Maximum age
16 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
No exclusion criteria

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
N/A
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
N/A
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
N/A
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
We will enrol 20 control and 100 experimental patients.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
3/09/2018
Actual
Date of last participant enrolment
Anticipated
27/12/2019
Actual
Date of last data collection
Anticipated
31/12/2019
Actual
Sample size
Target
120
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 9728 0
Lady Cilento Children's Hospital - South Brisbane
Recruitment postcode(s) [1] 18505 0
4101 - South Brisbane

Funding & Sponsors
Funding source category [1] 298371 0
Charities/Societies/Foundations
Name [1] 298371 0
Financial Markets Foundation for Children
Country [1] 298371 0
Australia
Funding source category [2] 298372 0
Charities/Societies/Foundations
Name [2] 298372 0
National Health and Medical Research Council - Project Grant
Country [2] 298372 0
Australia
Primary sponsor type
Government body
Name
The University of Queensland
Address
Naomi Epstein
Administrative Officer
Health and Biomedical Initiatives
Office of Sponsored Research
The University of Queensland
Brisbane Queensland 4072

Country
Australia
Secondary sponsor category [1] 297497 0
Hospital
Name [1] 297497 0
Children's Health Queensland Hospital and Health Service
Address [1] 297497 0
501 Stanley Street
South Brisbane
Queensland 4101

Postal address
PO Box 3474
South Brisbane
Queensland 4101
Country [1] 297497 0
Australia
Other collaborator category [1] 279888 0
Individual
Name [1] 279888 0
Dr Debbie A Long
Address [1] 279888 0
Nurse Researcher
Paediatric Intensive Care Unit | Division of Critical Care
Lady Cilento Children’s Hospital | Children's Health Queensland Hospital and Health Service
501 Stanley St, South Brisbane
PO Box 3474 South Brisbane QLD 4101

Country [1] 279888 0
Australia
Other collaborator category [2] 279889 0
Individual
Name [2] 279889 0
A/Prof Trent M Woodruff
Address [2] 279889 0
NHMRC Career Development Fellow
School of Biomedical Sciences
Faculty of Medicine
The University of Queensland
Brisbane Queensland 4072
Country [2] 279889 0
Australia
Other collaborator category [3] 279890 0
Individual
Name [3] 279890 0
Emeritus Professor Andrew W Boyd
Address [3] 279890 0
Faculty of Medicine
The University of Queensland
Herston Q 4006
Country [3] 279890 0
Australia
Other collaborator category [4] 279891 0
Individual
Name [4] 279891 0
Professor Perry Bartlett
Address [4] 279891 0
Queensland Brain Institute
The University of Queensland
St Lucia Q4072
Country [4] 279891 0
Australia
Other collaborator category [5] 279892 0
Individual
Name [5] 279892 0
Professor Jeff Lipman
Address [5] 279892 0
Burns,Trauma and Critical Care Research Centre
Level 8, UQ Centre for Clinical Research
School of Biomedical Sciences,
Faculty of Medicine
Herston Q 4029
Country [5] 279892 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299364 0
Children's Health Queensland Hospital and Health Service
Ethics committee address [1] 299364 0
Ethics committee country [1] 299364 0
Australia
Date submitted for ethics approval [1] 299364 0
27/11/2017
Approval date [1] 299364 0
06/12/2017
Ethics approval number [1] 299364 0
HREC/17/QRCH/275

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 2329 2329 0 0
/AnzctrAttachments/374283-HREC17QRCH275 ethics approval 061217.pdf (Ethics approval)
Attachments [2] 2330 2330 0 0
/AnzctrAttachments/374283-RESEARCH PROTOCOL - MICRODIALYSIS SEPTIC PATIENTS V1 17.11.17_MGC1.doc (Protocol)
Attachments [3] 2331 2331 0 0
/AnzctrAttachments/374283-Parent-Guardian Consent Form sepsis V1 17.11.17.doc (Participant information/consent)
Attachments [4] 2332 2332 0 0
/AnzctrAttachments/374283-Parent-Guardian Information Sheet Sepsis V2 12.12.17.doc (Participant information/consent)

Contacts
Principal investigator
Name 80190 0
A/Prof Mark G Coulthard
Address 80190 0
UQ Faculty, Level 7
Lady Cilento Children's Hospital
501 Stanley Street
South Brisbane Q4101
Country 80190 0
Australia
Phone 80190 0
+61730684674
Fax 80190 0
+61730684673
Email 80190 0
[email protected]
Contact person for public queries
Name 80191 0
Mark G Coulthard
Address 80191 0
UQ Faculty, Level 7
Lady Cilento Children's Hospital
501 Stanley Street
South Brisbane Q4101
Country 80191 0
Australia
Phone 80191 0
+61730684674
Fax 80191 0
+61730684673
Email 80191 0
[email protected]
Contact person for scientific queries
Name 80192 0
Mark G Coulthard
Address 80192 0
UQ Faculty, Level 7
Lady Cilento Children's Hospital
501 Stanley Street
South Brisbane Q4101
Country 80192 0
Australia
Phone 80192 0
+61730684674
Fax 80192 0
+61730684673
Email 80192 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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