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Evaluating treatment strategies for Gram-negative bloodstream infections

BALANCE+: A Platform Trial for Gram Negative Bloodstream Infections

Not applicable Interventional Sunnybrook Health Sciences Centre · NCT06537609

This study is testing different treatment options for hospitalized patients with Gram-negative bloodstream infections to see which ones work best and improve their recovery.

Quick facts

PhaseNot applicable
Study typeInterventional
Enrollment2500 (estimated)
Ages0 Years to 130 Years
SexAll
SponsorSunnybrook Health Sciences Centre Academic / other
Locations39 sites (Kogarah, New South Wales and 38 other locations)
Trial IDNCT06537609 on ClinicalTrials.gov

What this trial studies

BALANCE+ is an adaptive platform trial designed to assess various treatment strategies for patients hospitalized with Gram-negative bloodstream infections (GN BSIs). The trial employs an open-label, pragmatic design and utilizes Bayesian methods to evaluate multiple interventions, including antibiotic de-escalation and central line management. It aims to address critical questions in the management of GN BSIs, focusing on improving patient outcomes and combating antimicrobial resistance. The trial will continuously analyze data as patients are enrolled, allowing for adjustments based on interim results.

Who should consider this trial

Good fit: Ideal candidates for this study are hospitalized patients with a positive blood culture for a Gram-negative bacterium.

Not a fit: Patients who are receiving palliative care with no intention of active treatment or those who are moribund and not expected to survive beyond 72 hours may not benefit from this study.

Why it matters

Potential benefit: If successful, this trial could lead to more effective treatment strategies for Gram-negative bloodstream infections, ultimately improving patient outcomes and reducing mortality rates.

How similar studies have performed: Previous studies have shown promise in evaluating treatment strategies for bloodstream infections, but this platform trial approach is relatively novel and aims to address significant gaps in current research.

Eligibility criteria

Show full inclusion / exclusion 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

Where this trial is running

Kogarah, New South Wales and 38 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Gram-negative Bacteremia
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.