Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623001058662
Ethics application status
Approved
Date submitted
4/08/2023
Date registered
3/10/2023
Date last updated
3/10/2023
Date data sharing statement initially provided
3/10/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
DOSE CF Kids - a pharmacokinetic sub-study of antibiotics administered to children as part of the BEAT CF Platform Pulmonary Exacerbations Cohort.
Scientific title
DOSE CF Kids - opportunistic pharmacokinetic-pharmacodynamic (PK-PD) sub-study of antibiotic interactions in children enrolled in the BEAT CF Platform Pulmonary Exacerbations Cohort.
Secondary ID [1] 310104 0
None
Universal Trial Number (UTN)
Trial acronym
DOSE CF Kids
Linked study record
This a sub-study related to ACTRN12621000638831. All participants for this substudy must be enrolled in ACTRN12621000638831 prior to enrolment in DOSE CF Kids.

Health condition
Health condition(s) or problem(s) studied:
Cystic Fibrosis 330670 0
Condition category
Condition code
Respiratory 327486 327486 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Observation of the concentrations of intravenous (IV) antibiotics, as determined by the treating clinician, as treatment for a pulmonary exacerbation requiring intensive therapy (PERIT) in children with CF. The period of observation will correspond to the duration for which IV antibiotics are given for a particular pulmonary exacerbation, which is at the discretion of the treating clinician.
Blood samples for the DOSE CF substudy will be collected at the same time as the routine clinical bloods. This will be per the clinical schedule for blood sampling at each centre. A maximum of 3 samples per patient per day will be collected with a total maximum of 10 samples per patient during a course of IV antibiotics.
Sputum and urine samples will be collected from participants on prior to IV antibiotic commencement on day 1, and on day 7 of the IV antibiotic course.
Participants in DOSE CF will be children up to 18 years of age who are enrolled in the BEAT CF Cohort and are about to start a course of IV antibiotics to treat a pulmonary exacerbation.
Intervention code [1] 326502 0
Not applicable
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 335379 0
Percentage of time that the free drug concentration exceeds the minimum inhibitory concentration (MIC) of the bacteria causing infection.
Timepoint [1] 335379 0
At steady state i.e. more than 10 hours after treatment commencement
(Steady state = 5 x half life, half life = 2 hours)

Blood samples for this substudy will be collected using the convenience sampling method (extra sample taken at the same time as other clinically indicated blood tests), for up to 14 days post commencement of IV antibiotics.

Primary outcome [2] 335798 0
Cmax:MIC for IV aminoglycoside antibiotics used to treat PERITs in children with CF
Timepoint [2] 335798 0
At steady state i.e. more than 10 hours after treatment commencement
(Steady state = 5 x half life, half life = 2 hours)

Blood samples for this substudy will be collected using the convenience sampling method (extra sample taken at the same time as other clinically indicated blood tests), for up to 14 days post commencement of IV antibiotics.
Primary outcome [3] 335799 0
AUC24:MIC for IV glycopeptides and aminoglycoside antibiotics used to treat PERITs in children with CF
Timepoint [3] 335799 0
At steady state i.e. more than 10 hours after treatment commencement
(Steady state = 5 x half life, half life = 2 hours)

Blood samples for this substudy will be collected using the convenience sampling method (extra sample taken at the same time as other clinically indicated blood tests), for up to 14 days post commencement of IV antibiotics. A maximum of 10 samples per patient per pulmonary exacerbation will be collected throughout the duration of the study
Secondary outcome [1] 424139 0
Threshold for plasma antibiotic concentrations where the threshold may be based on the AUC24 (drug exposure), Cmax (peak concentration) and/or trough (lowest) antibiotic concentration.
Timepoint [1] 424139 0
Timepoints for Blood sampling post dose are not defined. Blood samples for this substudy will be collected using the convenience sampling method (extra sample taken at the same time as other clinically indicated blood tests), for up to 14 days post commencement of IV antibiotics. A maximum of 10 samples per patient per pulmonary exacerbation will be collected throughout the duration of the study
Secondary outcome [2] 424143 0
Change in CF lung total bacterial load as determined from sputum samples.
Timepoint [2] 424143 0
Prior to commencement of IV antibiotics at the beginning of the PERIT, and again on Day 7 to 10 of IV antibiotics.
Secondary outcome [3] 424144 0
Any relationship between antibiotic exposure (plasma concentration) and drug-related renal injury as measured using the Kidney disease improving global outcome (KDIGO) rating scale and using urinary biomarkers KIM-1 and CCL14.
Timepoint [3] 424144 0
Greater than or equal to 5 days after treatment commencement

Blood samples for this substudy will be collected using the convenience sampling method (extra sample taken at the same time as other clinically indicated blood tests), for up to 14 days post commencement of IV antibiotics.
Secondary outcome [4] 425694 0
Amount of air a person can force out of their lungs in 1 second (FEV1) as determined using spirometry.
Timepoint [4] 425694 0
The FEV1 readings will be those performed as part of routine clinical practice at each site. It is expected that FEV1 will be reported at the following timepoints:
On admission pre first dose of antibiotic, Days 7- 14, Day 30, Day 60, Day 180
Secondary outcome [5] 426742 0
Change in relative abundance of Pseudomonas spp as determined from sputum samples.
Timepoint [5] 426742 0
Prior to commencement of IV antibiotics at the beginning of the PERIT, and again on Day 7 to 10 of IV antibiotics.

Eligibility
Key inclusion criteria
1. Be enrolled in the BEAT CF PEx Cohort (ACTRN12621000638831)
2. Be aged up to <18 years old.
3. Support from responsible clinician for enrolment.
4. Written Informed consent to DOSE CF Kids, obtained from the patient or their legal representative.
Minimum age
0 Years
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
The child’s Responsible Clinician deems enrolment in DOSE CF Kids is not in their best interest

Study design
Purpose
Screening
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Population PKPD analysis will use NONMEM. A first-order conditional estimation method will be used to estimate pharmacokinetic parameters and their variability. Model evaluation will be based on graphical and statistical criteria, including goodness-of-fit plots and VPC.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
25/10/2023
Actual
Date of last participant enrolment
Anticipated
2/12/2024
Actual
Date of last data collection
Anticipated
14/07/2025
Actual
Sample size
Target
200
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 25173 0
The Royal Childrens Hospital - Parkville
Recruitment hospital [2] 25174 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [3] 25175 0
Queensland Children's Hospital - South Brisbane
Recruitment postcode(s) [1] 40843 0
3052 - Parkville
Recruitment postcode(s) [2] 40844 0
2145 - Westmead
Recruitment postcode(s) [3] 40845 0
4101 - South Brisbane

Funding & Sponsors
Funding source category [1] 314266 0
University
Name [1] 314266 0
University of Sydney
Country [1] 314266 0
Australia
Funding source category [2] 314284 0
Other Collaborative groups
Name [2] 314284 0
Murdoch Children's Research Institute
Country [2] 314284 0
Australia
Primary sponsor type
University
Name
University of Sydney
Address
Level 3, F23 Michael Spence Building, The University of Sydney NSW 2006
Country
Australia
Secondary sponsor category [1] 316205 0
None
Name [1] 316205 0
Address [1] 316205 0
Country [1] 316205 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313385 0
Child and Adolescent Health Services Human Research Ethics Committee
Ethics committee address [1] 313385 0
Ethics committee country [1] 313385 0
Australia
Date submitted for ethics approval [1] 313385 0
15/11/2022
Approval date [1] 313385 0
12/12/2022
Ethics approval number [1] 313385 0
RGS0000001265

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 127966 0
A/Prof Amanda Gwee
Address 127966 0
Royal Children’s Hospital, 3 West Clinical Offices50 Flemington Road Parkville, Victoria 3052
Country 127966 0
Australia
Phone 127966 0
+61 3 9345 5522
Fax 127966 0
+61 3 9345 4751
Email 127966 0
[email protected]
Contact person for public queries
Name 127967 0
Amanda Gwee
Address 127967 0
Royal Children’s Hospital, 3 West Clinical Offices50 Flemington Road Parkville, Victoria 3052
Country 127967 0
Australia
Phone 127967 0
+61 3 9345 5522
Fax 127967 0
+61 3 9345 4751
Email 127967 0
[email protected]
Contact person for scientific queries
Name 127968 0
Amanda Gwee
Address 127968 0
Royal Children’s Hospital, 3 West Clinical Offices50 Flemington Road Parkville, Victoria 3052
Country 127968 0
Australia
Phone 127968 0
+61 3 9345 5522
Fax 127968 0
+61 3 9345 4751
Email 127968 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All non-identifiable individual participant data will be made available subject to approval by the Coordinating Principal Investigator of BEAT CF and the DOSE CF Kids Substudy Principal Investigator.
When will data be available (start and end dates)?
From 3 months after publication of the DOSE CF Kids substudy final report.
No end date determined.
Available to whom?
Those who have submitted a request for data and provided a methodologically sound proposal for planned use of the data. Access will be granted at the discretion of the Coordinating Principal Investigator of BEAT CF and the DOSE CF Kids Substudy Principal Investigator.
Available for what types of analyses?
Analyses to achieve the aims in the approved proposal only
How or where can data be obtained?
Access via secure file transfer subject to approvals of the Coordinating Principal Investigator of BEAT CF ([email protected]) and the DOSE CF Kids Substudy Principal Investigator ([email protected]).


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.