Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
A database of clinical trials and their results from Australia, New Zealand, and other countries.
account_circle
Log in
to register or update your trial
search
Search for trials
Trial Review
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Download to PDF
Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT06537609
Registration number
NCT06537609
Ethics application status
Date submitted
25/07/2024
Date registered
5/08/2024
Date last updated
2/09/2025
Titles & IDs
Public title
A Platform Trial for Gram Negative Bloodstream Infections
Query!
Scientific title
BALANCE+: A Platform Trial for Gram Negative Bloodstream Infections
Query!
Secondary ID [1]
0
0
4369-1
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Gram-negative Bacteremia
0
0
Query!
Condition category
Condition code
Intervention/exposure
Study type
Interventional
Query!
Description of intervention(s) / exposure
Other interventions - De-escalation VS No De-escalation
Other interventions - Oral beta-lactams VS non beta-lactams
Other interventions - Central vascular catheter retention VS Central vascular catheter replacement
Other interventions - Cephalosporin VS Carbapenem for low risk AmpC organisms
Other interventions - Routine follow-up blood culture VS No routine follow-up blood culture
Active comparator: De-escalation VS No De-escalation -
Active comparator: Oral beta-lactams VS Oral Non-beta-lactams -
Active comparator: Central vascular catheter retention VS Central vascular catheter replacement -
Active comparator: Cephalosporin VS Carbapenem for low risk AmpC organisms -
Active comparator: Routine follow-up blood culture VS No routine follow-up blood culture -
Other interventions: De-escalation VS No De-escalation
No de-escalation group: continue to receive the same antibiotic that was started initially (as long as it is confirmed to be effective based on the blood culture sensitivity result). De-escalation is only allowed within 7 days if patient is being discharged from hospital.
De-escalation group: switched to narrower spectrum antibiotic (based on spectrum scale specified in protocol).
Other interventions: Oral beta-lactams VS non beta-lactams
Beta-lactam antibiotic: This can be, but not limited to, amoxicillin, amoxicillin-clavulanate, cephalexin, cefadroxil, or cefixime.
Non beta-lactam antibiotic: This can be ciprofloxacin, moxifloxacin, levofloxacin or trimethoprim-sulfamethoxazole.
Other interventions: Central vascular catheter retention VS Central vascular catheter replacement
Central vascular catheter replacement: the catheter will be changed by the treating team as soon as possible and within a maximum of 72 hours from blood culture finalization
Central vascular catheter retention: the catheter will not be changed and will be retained until it is non functional or no longer needed.
Other interventions: Cephalosporin VS Carbapenem for low risk AmpC organisms
Cephalosporin (ceftriaxone) at standard doses
Carbapenem (Meropenem or Ertapenem) at standard doses
Other interventions: Routine follow-up blood culture VS No routine follow-up blood culture
Routine follow-up blood culture: routine repeat blood collection 4 days from the index blood collection with positive bacteria.
No follow-up blood culture: no routine repeat blood collection 4 days from the index blood collection with positive bacteria
Query!
Intervention code [1]
0
0
Other interventions
Query!
Comparator / control treatment
Query!
Control group
Query!
Outcomes
Primary outcome [1]
0
0
Desirability of Outcome Ranking (DOOR) Ordinal Scale which incorporates death, reinfection, readmission, and for some domains incorporates a tie-breaker of new antimicrobial resistance (AMR).
Query!
Assessment method [1]
0
0
The primary outcome for each domain will use a Desirability of Outcome Ranking (DOOR) ordinal scale in which patients are categorized into the following mutually exclusive categories, ranked from best to worst status: 1. Alive with no reinfection or readmission. 2. Alive with reinfection OR readmission. 3. Alive with reinfection AND readmission. 4. Dead For the 3 antibiotic-related domains (the de-escalation versus no de-escalation domain, the beta-lactam versus non-beta-lactam domain, and the low risk AmpC domain) there will be an additional tie-breaker within ordinal levels 1, 2 and 3 based on whether there was new detection of antimicrobial resistance (AMR).
Query!
Timepoint [1]
0
0
90 days
Query!
Secondary outcome [1]
0
0
90-day mortality
Query!
Assessment method [1]
0
0
Query!
Timepoint [1]
0
0
90 days
Query!
Secondary outcome [2]
0
0
90-day re-infection
Query!
Assessment method [2]
0
0
Query!
Timepoint [2]
0
0
90 days
Query!
Secondary outcome [3]
0
0
90-day all cause readmission
Query!
Assessment method [3]
0
0
Query!
Timepoint [3]
0
0
90 days
Query!
Secondary outcome [4]
0
0
90-day AMR colonization/infection
Query!
Assessment method [4]
0
0
Query!
Timepoint [4]
0
0
90 days
Query!
Secondary outcome [5]
0
0
90-day Clostridioides difficile infection (CDI)
Query!
Assessment method [5]
0
0
Query!
Timepoint [5]
0
0
90 days
Query!
Secondary outcome [6]
0
0
30-day mortality
Query!
Assessment method [6]
0
0
Query!
Timepoint [6]
0
0
30 days
Query!
Secondary outcome [7]
0
0
60-day mortality
Query!
Assessment method [7]
0
0
Query!
Timepoint [7]
0
0
60 days
Query!
Secondary outcome [8]
0
0
Additional Secondary Outcomes for Individual Domains
Query!
Assessment method [8]
0
0
(i) De-escalation versus no de-escalation * change in total microbiome diversity between the day of randomization and discharge (or day 30 if earlier) * net change in resistome AMR burden between the day of randomization and discharge (or day 30 if earlier). (ii) Beta-lactam versus non-beta-lactam * antibiotic-related allergic reaction * antibiotic-related adverse event (iii) Central vascular catheter replacement versus retention * pneumothorax or thoracotomy tube insertion related to vascular catheter * clinically important bleeding * line associated thrombus * persistent bacteremia \>5d from initial index culture * secondary bloodstream infection with new bacterial or fungal organism (iv) Low-risk AmpC * isolation of ESBL producing organism or third generation cephalosporin resistant Gram negative organism * isolation of a carbapenem-resistant organism (v) Follow up blood culture domain * total duration of antibiotic therapy * hospital length of stay
Query!
Timepoint [8]
0
0
90 days
Query!
Eligibility
Key inclusion criteria
PLATFORM INCLUSION CRITERIA
Platform
* admitted to a participating hospital
* positive blood culture with Gram negative (GN) bacterium
Platform
Query!
Minimum age
0
Years
Query!
Query!
Maximum age
130
Years
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
Key exclusion criteria
* patient's goals of care are for palliation with no active treatment
* moribund patient, not expected to survive > 72 hours
* previously enrolled in the platform trial
* not eligible for any domain at the time of screening
DOMAIN SPECIFIC INCLUSION AND EXCLUSION CRITERIA
1. De-escalation versus no de-escalation domain
Inclusion Criteria
- included in BALANCE+ platform
Exclusion Criteria
* receiving an empiric antibiotic regimen at the time of blood culture finalization to which the GN pathogen(s) are not sensitive
* arbapenem-non-susceptible
* no de-escalation option due to any or all of:
* antimicrobial resistance
* allergies
* medical contraindications
* drug-drug interaction risk
* other relevant reason
* patients with a suspected or proven polymicrobial source of infection
* > 24 hours since index blood culture susceptibility results finalization
2. Beta-lactam versus non-beta-lactam oral/enteral treatment domain
Inclusion Criteria
* included in BALANCE+ platform
* initially treated with intravenous antibiotics, but clinical team transitioning patient to oral/enteral antibiotic within 7 days of starting treatment
Exclusion Criteria
* enrolled in an arm of another BALANCE+ platform domain which limits the use of oral/enteral therapy:
* no-de-escalation arm (patients in the no de-escalation arm cannot be randomized into this domain unless they are ready for discharge home, in which case de-escalation is allowable to oral agents at discharge)
* no non-beta-lactam options due to any or all of:
* resistance
* allergies
* medical contraindications
* drug-interaction risk
* other relevant reason
* no beta-lactam options due to any or all of:
* resistance
* allergies
* medical contraindications
* drug-interaction risk
* other relevant reason
* pregnancy
* already received >24 hours of oral antibiotics after index blood culture finalization
3. Central vascular catheter replacement domain
Inclusion Criteria
* included in BALANCE+ platform
* has an indwelling central vascular catheter that was already in place within the 48-hour period before the onset of bloodstream infection (i.e. is not a new catheter placed within 48 hours of the onset of infection)
Exclusion Criteria
* patient has no ongoing need for a central vascular catheter
* patient has definite indication for central vascular catheter removal
* ongoing septic shock with definite/probable line source
* concomitant S. aureus bacteremia
* concomitant candidemia
* local suppurative signs (severe redness, warmth, pain, swelling or fluctuance/collection) necessitating catheter removal, or other clinical evidence of infected line (e.g. imaging/echocardiographic findings)
4. Low-risk AmpC domain
Inclusion Criteria
* included in BALANCE+ platform
* positive blood culture with GN bacterium, of the following species: i. Serratia spp. ii Morganella spp. iii Providencia spp. iv Proteus spp. other than P.mirabilis
* organism is susceptible to ceftriaxone
Exclusion Criteria
* severe allergy to beta-lactams (e.g., type 4 hypersensitivity reaction or DRESS)
* baseline phenotypic non-susceptiblity to ceftriaxone
* more than 1 calendar day beyond availability of susceptibility results
5. Follow up blood culture domain
Inclusion Criteria
- included in BALANCE+ platform
Exclusion Criteria
* patient died or discharged from hospital prior to day 4
* blood culture already collected by the treating team at day 4±1
* >5 days since index positive blood culture collection
* definite indication for repeat blood culture testing
* concomitant S. aureus bacteremia
* concomitant Candidemia
* clinical suspicion for infective endocarditis
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Randomised controlled trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Open (masking not used)
Query!
Who is / are masked / blinded?
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Not applicable
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Recruiting
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
24/04/2024
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
1/04/2028
Query!
Actual
Query!
Sample size
Target
2500
Query!
Accrual to date
Query!
Final
Query!
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Query!
Recruitment hospital [1]
0
0
St George Hospital - Kogarah
Query!
Recruitment hospital [2]
0
0
John Hunter Hospital - New Lambton
Query!
Recruitment hospital [3]
0
0
Redcliffe Hospital - Redcliffe
Query!
Recruitment hospital [4]
0
0
Sunshine Coast University Hospital - Sunshine Coast
Query!
Recruitment hospital [5]
0
0
Monash Medical Center - Clayton
Query!
Recruitment hospital [6]
0
0
Fiona Stanley Hospital - Murdoch
Query!
Recruitment hospital [7]
0
0
St John of God - Murdoch
Query!
Recruitment postcode(s) [1]
0
0
2217 - Kogarah
Query!
Recruitment postcode(s) [2]
0
0
- New Lambton
Query!
Recruitment postcode(s) [3]
0
0
- Redcliffe
Query!
Recruitment postcode(s) [4]
0
0
- Sunshine Coast
Query!
Recruitment postcode(s) [5]
0
0
- Clayton
Query!
Recruitment postcode(s) [6]
0
0
- Murdoch
Query!
Recruitment outside Australia
Country [1]
0
0
Canada
Query!
State/province [1]
0
0
Alberta
Query!
Country [2]
0
0
Canada
Query!
State/province [2]
0
0
British Columbia
Query!
Country [3]
0
0
Canada
Query!
State/province [3]
0
0
Manitoba
Query!
Country [4]
0
0
Canada
Query!
State/province [4]
0
0
New Brunswick
Query!
Country [5]
0
0
Canada
Query!
State/province [5]
0
0
Newfoundland and Labrador
Query!
Country [6]
0
0
Canada
Query!
State/province [6]
0
0
Ontario
Query!
Country [7]
0
0
Canada
Query!
State/province [7]
0
0
Quebec
Query!
Country [8]
0
0
Colombia
Query!
State/province [8]
0
0
Cundinamarca
Query!
Country [9]
0
0
Israel
Query!
State/province [9]
0
0
Tel Aviv
Query!
Funding & Sponsors
Primary sponsor type
Other
Query!
Name
Sunnybrook Health Sciences Centre
Query!
Address
Query!
Country
Query!
Other collaborator category [1]
0
0
Government body
Query!
Name [1]
0
0
Canadian Institutes of Health Research (CIHR)
Query!
Address [1]
0
0
Query!
Country [1]
0
0
Query!
Ethics approval
Ethics application status
Query!
Summary
Brief summary
BALANCE+ is a perpetual multiple domain randomized controlled platform trial to evaluate various treatment strategies for Gram-negative bloodstream infections (GN BSIs). Each domain addresses critical questions in the management of GN BSIs, aiming to refine treatment strategies, enhance patient outcomes, and reduce antimicrobial resistance. The initial vanguard pilot RCT (NCT05893147) started on 29 August 2023 and has successfully completed the pilot phase on 24-Apr-2024. All patients enrolled in the vanguard phase are part of the main platform trial.
Query!
Trial website
https://clinicaltrials.gov/study/NCT06537609
Query!
Trial related presentations / publications
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
Nick Daneman, MD
Query!
Address
0
0
Sunnybrook Health Sciences Centre
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Nick Daneman, MD
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
4164806100
Query!
Fax
0
0
Query!
Email
0
0
[email protected]
Query!
Contact person for scientific queries
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
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT06537609
Download to PDF