Status:

RECRUITING

A Platform Trial for Gram Negative Bloodstream Infections

Lead Sponsor:

Sunnybrook Health Sciences Centre

Collaborating Sponsors:

Canadian Institutes of Health Research (CIHR)

Conditions:

Gram-negative Bacteremia

Eligibility:

All Genders

Up to 130 years

Phase:

NA

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...

Detailed Description

BALANCE+ is an adaptive platform trial evaluating multiple treatment options in patients admitted to the hospital due to Gram negative bloodstream infections (BSIs). It focuses on both cross-cutting a...

Eligibility Criteria

Inclusion

  • PLATFORM INCLUSION CRITERIA
  • Platform
  • admitted to a participating hospital
  • positive blood culture with Gram negative (GN) bacterium
  • Platform

Exclusion

  • 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
  • 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
  • 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
  • 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)
  • 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
  • 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

Key Trial Info

Start Date :

April 24 2024

Trial Type :

INTERVENTIONAL

Allocation :

ESTIMATED

End Date :

April 1 2028

Estimated Enrollment :

2500 Patients enrolled

Trial Details

Trial ID

NCT06537609

Start Date

April 24 2024

End Date

April 1 2028

Last Update

September 2 2025

Active Locations (36)

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Page 1 of 9 (36 locations)

1

St George Hospital

Kogarah, New South Wales, Australia, 2217

2

John Hunter Hospital

New Lambton, New South Wales, Australia

3

Redcliffe Hospital

Redcliffe, Queensland, Australia

4

Sunshine Coast University Hospital

Sunshine Coast, Queensland, Australia

A Platform Trial for Gram Negative Bloodstream Infections | DecenTrialz