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Trial registered on ANZCTR


Registration number
ACTRN12618000110280
Ethics application status
Approved
Date submitted
27/07/2015
Date registered
24/01/2018
Date last updated
24/01/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Beta-lactam pharmacokinetics in haematology patients with sepsis.
Scientific title
Evaluation of pharmacokinetic and clinical outcomes with standard empiric beta-lactam antibiotic dosing strategies in patients with febrile neutropenia being treated with intensive chemotherapy for haematological malignancies, including assessment of alterations in renal clearance in the setting of sepsis.
Secondary ID [1] 287150 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Febrile neutropenia 295709 0
Haematological malignancy 295947 0
Sepsis 295948 0
Condition category
Condition code
Infection 295989 295989 0 0
Studies of infection and infectious agents
Cancer 296221 296221 0 0
Leukaemia - Acute leukaemia
Cancer 296222 296222 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
1. Assessment of pharmacokinetic/pharmacodynamic outcomes of beta lactam antibiotics which are prescribed in the course of standard care of neutropenic fever. Specifically, two drug levels will be collected in steady-state to calculate the time during the dosing interval for which the unbound antibiotic concentration remains above the desired MIC.
2. Assessment of clinical outcomes, including rate of resolution of infection, duration of antibiotic treatment, length of hospital stay, overall survival. The maximum period of observation will be 30 days.
3. Assessment of changes in creatinine clearance with the onset of sepsis, using timed urine collection before and after onset of fever.
Intervention code [1] 292420 0
Not applicable
Comparator / control treatment
Nil
Control group
Uncontrolled

Outcomes
Primary outcome [1] 295660 0
The achievement of target serum beta-lactam concentrations as measured by the time during the dosing interval for which the unbound antibiotic concentration remains above the desired minimum inhibitory concentration (fTMIC).
Timepoint [1] 295660 0
Two samples collected in steady state (ie at least 24 hours after commencing antibiotic): one at mid-dosing interval and one at end of dosing interval.
Secondary outcome [1] 316137 0
Creatinine clearance at baseline and following the onset of sepsis, calculated using paired serum and 24 hour urine samples.
Timepoint [1] 316137 0
At enrolment and again at onset of first fever.
Secondary outcome [2] 316850 0
Time to resolution of infection, defined by time to normalisation of temperature and haemodynamic parameters. This information will be collected from the patient's hospital record.
Timepoint [2] 316850 0
Days from time of first fever. This information will be collected from the patient's hospital record.
Secondary outcome [3] 316851 0
Duration of antibiotic treatment. This information will be collected from the patient's hospital record.
Timepoint [3] 316851 0
Days from time of initiation of antibiotic. This information will be collected from the patient's hospital record.
Secondary outcome [4] 316852 0
Duration of in-patient hospital stay. This information will be collected from the patient's hospital record.
Timepoint [4] 316852 0
Days from time of first fever to discharge. This information will be collected from the patient's hospital record.
Secondary outcome [5] 316853 0
Overall survival. This information will be collected from the patient's hospital record.
Timepoint [5] 316853 0
30 days from time of first fever. This information will be collected from the patient's hospital record.

Eligibility
Key inclusion criteria
Able to provide written informed consent;
Age equal to or greater than 18 years;
Receiving intensive chemotherapy for acute leukaemia or high-grade lymphoma
-Intensive chemotherapy is defined as a treatment regimen that is expected to produce neutropenia (absolute neutrophil count <1x10^9/L) for at least 7 days duration.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Inadequate venous access to facilitate sample collection;
Pre-existing renal failure (eGFR <60mL/min);
Known allergy/ hypersensitivity to all study beta-lactam antibiotics;
Prior anaphylaxis to penicillin;
Pregnancy.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Data analysis is complete
Reason for early stopping/withdrawal
Participant recruitment difficulties
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)
QLD
Recruitment hospital [1] 9642 0
Royal Brisbane & Womens Hospital - Herston
Recruitment postcode(s) [1] 18404 0
4029 - Herston

Funding & Sponsors
Funding source category [1] 291719 0
Charities/Societies/Foundations
Name [1] 291719 0
RBWH Foundation
Address [1] 291719 0
Block 20 Royal Brisbane and Women’s Hospital
Butterfield St
Herston QLD 4006
Country [1] 291719 0
Australia
Primary sponsor type
Hospital
Name
Cancer Care Services, RBWH
Address
Level 5
Joyce Twedell Bldg
Royal Brisbane Hospital
Butterfield St
Herston QLD 4006
Country
Australia
Secondary sponsor category [1] 290391 0
None
Name [1] 290391 0
nil
Address [1] 290391 0
Country [1] 290391 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293241 0
RBWH HREC
Ethics committee address [1] 293241 0
Human Research Ethics Office
Level 7, Block 7
Royal Brisbane and Women's Hospital
Herston Rd
Herston QLD 4006
Ethics committee country [1] 293241 0
Australia
Date submitted for ethics approval [1] 293241 0
Approval date [1] 293241 0
22/04/2015
Ethics approval number [1] 293241 0
HREC/15/QRBW/104

Summary
Brief summary
The primary purpose of this study is to evaluate the pharmacokinetic and pharmacodynamic outcomes with standard beta lactam antibiotics given to patients with febrile neutropenia as a result of intensive chemotherapy. Who is it for? You may be eligible to join this study if you are aged 18 or over, and have been prescribed a course of intensive chemotherapy for acute leukaemia or high-grade lymphoma. Study details This is an observational study, so all participants will undergo the standard care prescribed to them by their treating physician. To assess outcomes, blood samples will be taken at baseline, two samples approximately 24 hours after commencement of antibiotics and at onset of fever, and one urine sample will also be taken 24 hours after onset of fever. Additional information including length of antibiotic use and hospital stay will also be noted. It is hoped that the findings of this trial will aid understanding of the distribution and levels of this class of antibiotics in the body, and their impact on outcomes in patients with febrile neutropenia as a result of intensive chemotherapy.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 59030 0
Dr Nicholas Weber
Address 59030 0
Level 5 Joyce Twedell Building
Royal Brisbane and Women's Hospital
Butterfield St
Herston QLD 4006
Country 59030 0
Australia
Phone 59030 0
+61736468111
Fax 59030 0
Email 59030 0
nicholas.weber@health.qld.gov.au
Contact person for public queries
Name 59031 0
Dr Nicholas Weber
Address 59031 0
Level 5 Joyce Twedell Building
Royal Brisbane and Women's Hospital
Butterfield St
Herston QLD 4006
Country 59031 0
Australia
Phone 59031 0
+61736468111
Fax 59031 0
Email 59031 0
nicholas.weber@health.qld.gov.au
Contact person for scientific queries
Name 59032 0
Dr Nicholas Weber
Address 59032 0
Level 5 Joyce Twedell Building
Royal Brisbane and Women's Hospital
Butterfield St
Herston QLD 4006
Country 59032 0
Australia
Phone 59032 0
+61736468111
Fax 59032 0
Email 59032 0
nicholas.weber@health.qld.gov.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary