Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620001108909
Ethics application status
Approved
Date submitted
25/08/2020
Date registered
26/10/2020
Date last updated
26/10/2020
Date data sharing statement initially provided
26/10/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Is 7 days of antibiotics as effective as 14 days of antibiotics for the 'cure' of urinary sepsis: an observational sub-study of the BALANCE Study.
Scientific title
Impact of a shorter (7 days) compared with a longer (14d) duration of antimicrobial therapy on the treatment of bacteraemic urinary sepsis, measured by microbiological success after the completion of therapy: A sub-study of the BALANCE study.
Secondary ID [1] 302136 0
Nil Known
Universal Trial Number (UTN)
U1111-1256-0874
Trial acronym
BALANCE
Linked study record
This record is a sub-study of NCT03005145,

Health condition
Health condition(s) or problem(s) studied:
Urinary tract infection
 318766 0
Urinary sepsis 318767 0
Bacteraemia 318768 0
Condition category
Condition code
Infection 316780 316780 0 0
Studies of infection and infectious agents
Renal and Urogenital 316781 316781 0 0
Other renal and urogenital disorders

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
This is an observational sub-study of the main BALANCE Study (NCT03005145). The intervention in the main BALANCE study is a shorter duration antimicrobial therapy (7d) compared with a longer duration (14d).
This sub-study is gathering enhanced data and additional end-points on participants with a urinary tract source of sepsis, who are enrolled BALANCE. The primary outcome of this sub-study is measured with the collection of a mid-stream urine sample 6-12 days after completion of study-defined antimicrobial therapy. Additional data on symptoms and clinical outcomes are measured by survey questions at the same time-point and at 90 days after the onset of bacteraemia.
Intervention code [1] 318716 0
Not applicable
Comparator / control treatment
The comparator and control are as defined by the main BALANCE study. The study is comparing short duration (7d) antimicrobial therapy to a longer duration (14d) for the treatment of bacteraemia. The choice of antimicrobial agent and route of therapy are not study-defined and are made by the treating clinician. This sub-study is observational and has no additional comparator or control interventions.
Control group
Active

Outcomes
Primary outcome [1] 324899 0
The proportion of patients meeting the 'microbiological success' endpoint on a urine sample 6-12 days after completion of study defined antimicrobial therapy. Microbiological success is defined as a urine sample reported as having ‘no-growth’, ‘no significant growth’ (or the equivalent local terminology), on bacterial culture.
Timepoint [1] 324899 0
The primary endpoint is measured at the collection of a test-of-cure urine sample. A single sample will be collected in the window of 6-12 days after the completion of the BALANCE study defined antimicrobial therapy course. This is a 7 day window commencing 5 full days after completion of antimicrobials.
The exact timing of this window will vary depending on the duration of antimicrobial therapy. For example, if a participants receive exactly 7 days of antimicrobial in the BALANCE study, this will window be days 13-19 of the main BALANCE study. If a participants receiving exactly 14 days of antimicrobials this window will be days 20-26 of the main BALANCE study.
Secondary outcome [1] 386161 0
The proportion of patients with clinical success defined as resolution of symptoms and signs of urinary tract infection, as measured by a clinical questionnaire collected in the same time-window as the test-of-cure sample.
Timepoint [1] 386161 0
This will be measured in the same test-of-cure time-window of 6-12 days after the completion of the BALANCE study defined antimicrobial therapy course (This is a 7 day window commencing 5 full days after completion of antimicrobials).
Secondary outcome [2] 386162 0
The proportion of patients exhibiting clinical success AND microbiological success at the test-of-cure time-point.
Timepoint [2] 386162 0
This will be measured in the same test-of-cure time-window of 6-12 days after the completion of the BALANCE study defined antimicrobial therapy course (This is a 7 day window commencing 5 full days after completion of antimicrobials).
Secondary outcome [3] 386163 0
Proportion of patients alive at 90 days after the onset of bacteraemia
Timepoint [3] 386163 0
This will be measured at 90 days from the onset of bacteraemia
Secondary outcome [4] 386164 0
Participant reported recurrence (and/or confirmed) of urinary tract infection, in the 90 days after the onset of bacteraemia, as reported by the participant in a questionnaire 90 days after onset of bacteraemia
Timepoint [4] 386164 0
This will be measured at 90 days from the onset of bacteraemia
Secondary outcome [5] 386165 0
Participant receipt of non trial-specified antimicrobial therapy, as reported by the participant in a questionnaire 90 days after onset of bacteraemia
Timepoint [5] 386165 0
This will be measured at 90 days from the onset of bacteraemia

Eligibility
Key inclusion criteria
1) The participant has been enrolled and randomised in the BALANCE study

2) The source of bacteraemia is most likely to originate from the urinary tract as evidenced by:
a. The enrolling clinician believes that the urinary tract is the ‘most likely’ source of the bacteraemia
AND
b. Routine clinical work-up has not identified another ‘probable’ source of the bacteraemia

3) The participant has a urine microscopy and culture result on a fresh urine sample (not from the drainage bag of a urinary catheter) supporting the urinary tract as a source of bacteraemia as evidenced by the presence of A & B:
a. The urine culture has been collected during the same episode of acute illness associated with the bacteraemia.
AND
b. Microbiological findings are supportive of a urinary source. An acceptable supportive result is ANY of the three criteria below:
i. A urine culture has isolated the same bacteria (genus & species) as the blood culture. The antimicrobial resistance phenotype (antibiotic susceptibility pattern) may vary from the blood isolate.
OR
ii. A urine culture has isolated mixed bacteria for which individual species have not been characterised
OR
iii. A urine culture collected after antimicrobial therapy demonstrates a WCC count consistent with a urinary source of sepsis, based on local interpretation guidelines
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Male participants with suspected or confirmed prostatitis
2) Participants with an Ileal loop or vesicoureteric reflux
3) Participants who are unable or unwilling to provide a follow-up urine sample for culture within the specified study time-frame.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
This is a sub-study of the main BALANCE trial. Analysis will be by assigned groups (intention to treat). For the primary analysis a modified intention to treat population will be used. It will include only patients with an available test-of-cure sample. Any participant who has re-commenced antimicrobial therapy between the cessation of trial specified antimicrobials and the collection of the test-of-cure sample will be considered to not have met the primary outcome.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/11/2020
Actual
Date of last participant enrolment
Anticipated
31/12/2022
Actual
Date of last data collection
Anticipated
31/03/2023
Actual
Sample size
Target
284
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,NT,QLD,WA,VIC
Recruitment outside Australia
Country [1] 22891 0
Canada
State/province [1] 22891 0

Funding & Sponsors
Funding source category [1] 306562 0
Government body
Name [1] 306562 0
National Health & Medical Research Council, Australia
Country [1] 306562 0
Australia
Primary sponsor type
University
Name
Monash University
Address
Monash University, School of Clinical Sciences at Monash Health,
Level 5, E block, 246 Clayton Rd, Clayton, Victoria, Australia, 3168
Country
Australia
Secondary sponsor category [1] 307084 0
None
Name [1] 307084 0
Address [1] 307084 0
Country [1] 307084 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306747 0
Monash Health HREC
Ethics committee address [1] 306747 0
246 Clayton Rd, Clayton, Victoria, Australia, 3168
Ethics committee country [1] 306747 0
Australia
Date submitted for ethics approval [1] 306747 0
29/06/2020
Approval date [1] 306747 0
08/07/2020
Ethics approval number [1] 306747 0
RES-17-0000-403A (Amendment June 2020)

Summary
Brief summary
The BALANCE study is a randomised clinical trial comparing 7 to 14 days of antimicrobial therapy for bacteraemia. This sub-study is designed to determine whether patients enrolled in the main study, with a urinary source of their bacteraemia (urinary sepsis/urinary-tract infection), are as likely to be cured from their urinary-tract infection when treated with a short duration (7d) antimicrobial therapy, as compared with a longer duration (14d) of therapy.
Demonstrating a clinical cure of the primary source of infection is important in UTI. If microbiological cure of the infection is not achieved, patients remain at increased risk of recurrent urinary tract infection and sepsis. If the BALANCE study demonstrates non-inferiority of 7 days duration antimicrobial therapy, further data supporting non-inferiority of cure for UTI will enhance the generalisability and clinician acceptance of reduced duration antimicrobial therapy.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 104886 0
A/Prof Benjamin A Rogers
Address 104886 0
Monash Infectious Diseases
Level 3, Monash Medical Centre
246 Clayton Road
Clayton, Victoria, 3168
Country 104886 0
Australia
Phone 104886 0
+61 395944564
Fax 104886 0
Email 104886 0
[email protected]
Contact person for public queries
Name 104887 0
A/Prof Benjamin A Rogers
Address 104887 0
Monash Infectious Diseases
Level 3, Monash Medical Centre
246 Clayton Road
Clayton, Victoria, 3168
Country 104887 0
Australia
Phone 104887 0
+61 395944564
Fax 104887 0
Email 104887 0
[email protected]
Contact person for scientific queries
Name 104888 0
A/Prof Benjamin A Rogers
Address 104888 0
Monash Infectious Diseases
Level 3, Monash Medical Centre
246 Clayton Road
Clayton, Victoria, 3168
Country 104888 0
Australia
Phone 104888 0
+61 395944564
Fax 104888 0
Email 104888 0
[email protected]

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
8928Study protocol  [email protected]
8929Informed consent form  [email protected]
8931Ethical approval  [email protected]



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.