A Platform Trial for Gram Negative Bloodstream Infections
BALANCE+
BALANCE+: A Platform Trial for Gram Negative Bloodstream Infections
1 other identifier
interventional
2,500
5 countries
39
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable
Started Apr 2024
Longer than P75 for not_applicable
39 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
April 24, 2024
CompletedFirst Submitted
Initial submission to the registry
July 25, 2024
CompletedFirst Posted
Study publicly available on registry
August 5, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
April 1, 2028
February 10, 2026
August 1, 2025
2.9 years
July 25, 2024
February 6, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
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).
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).
90 days
Secondary Outcomes (8)
90-day mortality
90 days
90-day re-infection
90 days
90-day all cause readmission
90 days
90-day AMR colonization/infection
90 days
90-day Clostridioides difficile infection (CDI)
90 days
- +3 more secondary outcomes
Study Arms (5)
De-escalation VS No De-escalation
ACTIVE COMPARATOROral beta-lactams VS Oral Non-beta-lactams
ACTIVE COMPARATORCentral vascular catheter retention VS Central vascular catheter replacement
ACTIVE COMPARATORCephalosporin VS Carbapenem for low risk AmpC organisms
ACTIVE COMPARATORRoutine follow-up blood culture VS No routine follow-up blood culture
ACTIVE COMPARATORInterventions
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.
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).
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.
Cephalosporin (ceftriaxone) at standard doses Carbapenem (Meropenem or Ertapenem) at standard doses
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
Eligibility Criteria
You may qualify if:
- admitted to a participating hospital
- positive blood culture with Gram negative (GN) bacterium
You may not qualify if:
- 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
- De-escalation versus no de-escalation domain
- \- included in BALANCE+ platform
- 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
- +45 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Clínica Universidad de La Sabanacollaborator
- Universidad de La Sabana, Colombiacollaborator
- Aotearoa Clinical Trialscollaborator
- Sunnybrook Health Sciences Centrelead
- Canadian Institutes of Health Research (CIHR)collaborator
Study Sites (39)
St George Hospital
Kogarah, New South Wales, 2217, Australia
John Hunter Hospital
New Lambton, New South Wales, Australia
Royal Brisbane and Women's Hospital
Herston, Queensland, 4006, Australia
Redcliffe Hospital
Redcliffe, Queensland, Australia
Sunshine Coast University Hospital
Sunshine Coast, Queensland, Australia
Monash Medical Center
Clayton, Victoria, Australia
Fiona Stanley Hospital
Murdoch, Western Australia, Australia
St John of God
Murdoch, Western Australia, Australia
Foothills Hospital
Calgary, Alberta, Canada
Peter Lougheed Centre
Calgary, Alberta, Canada
Rockyview General Hospital
Calgary, Alberta, Canada
South Health Campus
Calgary, Alberta, Canada
University of Alberta
Edmonton, Alberta, Canada
Surrey Memorial Hospital
Surrey, British Columbia, Canada
Vancouver General Hospital
Vancouver, British Columbia, Canada
Grace Hospital
Winnipeg, Manitoba, Canada
Health Sciences Centre
Winnipeg, Manitoba, Canada
St. Boniface Hospital
Winnipeg, Manitoba, Canada
Dr. Everett Chalmers Regional Hospital
Fredericton, New Brunswick, Canada
Eastern Regional Health Authority
St. John's, Newfoundland and Labrador, Canada
Trillium Health Partners - Mississauga Hospital
Mississauga, Ontario, Canada
Humber River Health system
North York, Ontario, Canada
North York General Hospital
North York, Ontario, Canada
The Ottawa Hospital
Ottawa, Ontario, Canada
Niagara Health System
St. Catharines, Ontario, Canada
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N3M5, Canada
Michael Garron Hospital
Toronto, Ontario, Canada
Mount Sinai Hospital
Toronto, Ontario, Canada
St. Joseph's Health Centre
Toronto, Ontario, Canada
University Health Network
Toronto, Ontario, Canada
CHU de Québec - Université Laval
Laval, Quebec, Canada
Hôpital de la Cité de la Santé
Laval, Quebec, Canada
Montreal General Hospital- McGill
Montreal, Quebec, Canada
Royal Victoria Hospital- McGill
Montreal, Quebec, Canada
Université de Sherbrooke
Sherbrooke, Quebec, Canada
Centre hospitalier affilié universitaire régional (CHAUR)
Trois-Rivières, Quebec, G8Z 3R9, Canada
Universidad de La Sabana
Chía, Cundinamarca, Colombia
Sheba Medical Center
Ramat Gan, Tel Aviv, Israel
Middlemore Hospital
Auckland, Auckland, 2025, New Zealand
Study Officials
- PRINCIPAL INVESTIGATOR
Nick Daneman, MD
Sunnybrook Health Sciences Centre
- PRINCIPAL INVESTIGATOR
Rob Fowler, MD
Sunnybrook Health Sciences Centre
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Clinician Scientist
Study Record Dates
First Submitted
July 25, 2024
First Posted
August 5, 2024
Study Start
April 24, 2024
Primary Completion (Estimated)
April 1, 2027
Study Completion (Estimated)
April 1, 2028
Last Updated
February 10, 2026
Record last verified: 2025-08