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Trial registered on ANZCTR


Registration number
ACTRN12617000020381
Ethics application status
Approved
Date submitted
7/04/2015
Date registered
5/01/2017
Date last updated
25/11/2019
Date data sharing statement initially provided
25/11/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
The ADP-TRAUMA Trial A randomised controlled clinical trial of Augmented Dosing of Piperacillin-tazobactam in TRAUMA patients with suspected or confirmed infection
Scientific title
The ADP-TRAUMA Trial A randomised controlled clinical trial of Augmented Dosing of Piperacillin-tazobactam in TRAUMA patients with suspected or confirmed infection
Secondary ID [1] 286459 0
The ADP-TRAUMA Trial
Universal Trial Number (UTN)
Trial acronym
The ADP-TRAUMA Trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Trauma 301266 0
Infection 301267 0
Condition category
Condition code
Infection 301024 301024 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Please refer to Appendix A table in attachment 1 on ANZCTR record.
Following randomisation, study participants will receive either standard prescription piperacillin-tazobactam, or augmented dosing, based on an ‘ARC Dose Optimisation Protocol’ . APPENDIX A-Protocol
An 8-hr urinary creatinine clearance measured on Day 1, and then every alternate day post randomisation, will be used to optimise therapy in those patients randomised to the augmented dosing strategy. The total duration of therapy will be at the discretion of the treating clinician, although augmented dosing will cease on Day 7, or discharge from the ICU.

In those randomised to standard prescription, this will utilise the current dosing strategies routinely employed at each participating institution. This typically involves intermittent administration of 4.5g IV piperacillin-tazobactam every 6 to 8 hours. Optimisation of dosing on the basis of CLCR measurements is not routinely performed at either site. Those patients randomised to the ARC Dose Optimisation protocol (See appendix 1) will commence a continuous infusion (over a 24 hour period) of their currently prescribed dose. That is, if a patient is prescribed 4.5g IV piperacillin-tazobactam every 6 hours, a bag of 250mls 0.9% Sodium Chloride will be prepared with 4 doses of 4.5g IV piperacillin-tazobactam to be administered continuously. All patients randomised to the ARC protocol will receive the total daily antibiotic dose delivered over 24hrs in a 250ml bag of Sodium Chloride 0.9%.
Standard care dosing is to be delivered as per each units usual drug dosing policy. Dosing is dependent on the clinicians prescription for the first study dosing period.
Intervention code [1] 296597 0
Treatment: Drugs
Comparator / control treatment
In those randomised to standard prescription, this will utilise the current dosing strategies routinely employed at each participating institution. This typically involves intermittent administration of 4.5g IV piperacillin-tazobactam every 6 to 8 hours. Standard care dosing is to be delivered as per each units usual drug dosing policy. Dosing is dependent on the clinicians prescription for the first study dosing period.
The protocol is attached to the ANZCTR form.
Control group
Active

Outcomes
Primary outcome [1] 300569 0
Primary:
Unbound piperacillin plasma concentration to MIC ratios determined at 24-48hrs and 120-144hrs after randomisation, and scored as a dichotomous variable (e.g. = MIC or < MIC).
Timepoint [1] 300569 0
Determined at 24-48hrs and 120-144hrs after randomisation, and scored as a dichotomous variable.
Secondary outcome [1] 329986 0
Clinical cure at 14-days post randomisation (scored as a categorical variable)
Clinical response will be assessed as follows:
1. Resolution – disappearance of all signs and symptoms related to the infection
2. Improvement – a marked or moderate reduction in the severity and/or number of signs and symptoms of infection
3. Failure – insufficient lessening of the signs and symptoms of infection to qualify as improvement, including death or indeterminate (no evaluation possible, for any reason).

For participants discharged from the ICU prior to the test of cure date, clinical response will be evaluated by review of the patient record for the test of cure date (midnight to midnight) as follows:
1. Resolution – absence of any SIRS criteria attributable to infection
2. Improvement – only 1 SIRS criterion at any one time that is attributable to infection
3. Failure – 2 or more SIRS criteria met concurrently and attributable to infection.

If the subject has a separate episode of infection on the test of cure date, clinical response will be rated for any day (midnight to midnight) in the preceding 7 days. The best clinical response during this period will be recorded. Clinical cure is defined as follows:
1. Resolution – absence of any SIRS criteria attributable to infection
2. All other findings (i.e., sum of 2 and 3 above)
Timepoint [1] 329986 0
14 days post randomisation
Secondary outcome [2] 329987 0
ICU-free days at day 28 post randomisation (scored as a continuous variable) by calculating the number of days discharged from ICU to day 28 since randomisation into the study.
Timepoint [2] 329987 0
Up to 28 days post randomisation

Eligibility
Key inclusion criteria
Any patient admitted to the ICU post multi-trauma, receiving piperacillin-tazobactam for presumed or confirmed infection.
Inclusion Criteria:

1. Age greater than or equal to 18 and less than or equal to 50 years
2. Admission post trauma
3. Informed consent is obtained from the patient or surrogate decision maker
4. The patient is anticipated to require ICU care beyond the next calendar day
5. Plasma creatinine concentration < 100 micromol/L on the day of randomisation
6. Presence of an indwelling urinary catheter (IDC)
Minimum age
18 Years
Maximum age
50 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

1. Evidence of acute kidney injury – as per the RIFLE criteria
2. Evidence of acute liver injury – defined as an AST or ALT > 5 x upper limit of normal (ULN), or AST or ALT > 3 x ULN with associated total bilirubin > 2 x ULN
3. Evidence of active haemorrhage – defined by a fall in haemoglobin concentration > 20g/L or the need for > 2 units RBC in the preceding 24hrs
4. Increased risk of bleeding – defined by a platelet count < 50, INR or aPTT > 2 x ULN
5. Extremes of body size – defined as a body mass index (BMI) < 16 or greater than and equal to 40 kg/m2
6. Pregnancy
7. Treatment intent is palliative
8. Death is deemed imminent and inevitable
9. Known hypersensitivity to piperacillin-tazobactam
10. Has received piperacillin-tazobactam therapy for > 24hrs prior to randomisation
11. Not eligible for Medicare

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



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Pharmacokinetics / pharmacodynamics
Statistical methods / analysis
Sample Size

Based on 50% fT>MIC being achieved in 60% of patients receiving standard dosing, and an improvement in target attainment to 90% in those receiving augmented dosing, with a power of 80%, and alpha error of 0.05, a sample size of 64 patients (32 in each group) is required.

Analysis

All analyses will be conducted on an intention-to-treat basis without adjustment for baseline variables. Differences in outcome variables will be compared using t-test and Chi-Squared test as appropriate if normally distributed and using non-parametric equivalents if non-normally distributed. No interim analysis is planned. Analysis will primarily be conducted using SPSS version 17 (Chicago, IL, USA).

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
Actual
15/07/2015
Date of last participant enrolment
Anticipated
31/12/2017
Actual
29/08/2017
Date of last data collection
Anticipated
31/01/2018
Actual
31/12/2017
Sample size
Target
64
Accrual to date
Final
20
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 7085 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [2] 7086 0
The Alfred - Prahran
Recruitment postcode(s) [1] 14814 0
4029 - Herston
Recruitment postcode(s) [2] 14815 0
3004 - Prahran

Funding & Sponsors
Funding source category [1] 291027 0
University
Name [1] 291027 0
The Univerity of Queensland
Country [1] 291027 0
Australia
Primary sponsor type
University
Name
The Univerity of Queensland
Address
Cumbrae-Stewart building
Research road Brisbane Qld 4072
Country
Australia
Secondary sponsor category [1] 294045 0
None
Name [1] 294045 0
Address [1] 294045 0
Country [1] 294045 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296481 0
The Royal Brisbane and Women's Hospital
Ethics committee address [1] 296481 0
Ethics committee country [1] 296481 0
Australia
Date submitted for ethics approval [1] 296481 0
03/03/2015
Approval date [1] 296481 0
27/05/2015
Ethics approval number [1] 296481 0
HREC/15/QRBW/14

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 1311 1311 0 0
/AnzctrAttachments/368292-ADP_Trauma_Version 3 dated 29APR16_clean.pdf (Protocol)

Contacts
Principal investigator
Name 56226 0
A/Prof Andrew Udy
Address 56226 0
Consultant Intensivist, Department of Intensive Care and Hyperbaric Medicine, The Alfred Hospital, 4 Commercial road Melbourne Victoria 3004
Country 56226 0
Australia
Phone 56226 0
+61 3 9076 2000
Fax 56226 0
Email 56226 0
Andrew@Udy.com
Contact person for public queries
Name 56227 0
Jason Roberts
Address 56227 0
Burns, Trauma, and Critical Care Research Center, The University of Queensland, Royal Brisbane and Women’s Hospital, Herston Road, Level 9, UQ Health Sciences Bldg
Royal Brisbane and Women's Hospital QLD 4029
Country 56227 0
Australia
Phone 56227 0
+61 7 3646 8894
Fax 56227 0
Email 56227 0
j.roberts2@uq.edu.au
Contact person for scientific queries
Name 56228 0
Andrew Udy
Address 56228 0
Consultant Intensivist, Department of Intensive Care and Hyperbaric Medicine, The Alfred Hospital, 4 Commercial road Melbourne Victoria 3004
Country 56228 0
Australia
Phone 56228 0
+61 3 9076 2000
Fax 56228 0
Email 56228 0
Andrew@Udy.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Undecided


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.