RECRUITING Not applicable ClinicalTrials.gov

A Platform Trial for Gram Negative Bloodstream Infections

Sponsor: Sunnybrook Health Sciences Centre • ClinicalTrials.gov ID: NCT06537609

Registry updated: 2026-09-04

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Description

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.

Interventions

De-escalation VS No De-escalation (Other)
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).
Oral beta-lactams VS non beta-lactams (Other)
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.
Central vascular catheter retention VS Central vascular catheter replacement (Other)
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.
Cephalosporin VS Carbapenem for low risk AmpC organisms (Other)
Cephalosporin (ceftriaxone) at standard doses Carbapenem (Meropenem or Ertapenem) at standard doses
Routine follow-up blood culture VS No routine follow-up blood culture (Other)
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

PLATFORM INCLUSION CRITERIA Platform Inclusion Criteria: * admitted to a participating hospital * positive blood culture with Gram negative (GN) bacterium Platform 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

Conditions

Gram-negative Bacteremia

Locations

St George Hospital — Kogarah, New South Wales, Australia
John Hunter Hospital — New Lambton, New South Wales, Australia
Royal Brisbane and Women's Hospital — Herston, Queensland, 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, 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, Canada
Universidad de La Sabana — Chía, Cundinamarca, Colombia
Sheba Medical Center — Ramat Gan, Tel Aviv, Israel
Middlemore Hospital — Auckland, Auckland, New Zealand

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Data sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

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