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A Platform Trial for Gram Negative Bloodstream Infections

ConditionGram-negative Bacteremia
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age0-130
SponsorSunnybrook Health Sciences Centre

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

admitted to a participating hospital

positive blood culture with Gram negative (GN) bacterium

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

  • De-escalation VS No De-escalation

    Other intervention

    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 intervention

    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 intervention

    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 intervention

    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 intervention

    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

Treatment groups

2,500 Participants
are divided into 5 treatment groups
Group A: De-escalation VS No De-escalationActive comparator 1 intervention
Group B: Oral beta-lactams VS Oral Non-beta-lactamsActive comparator 1 intervention
Group C: Central vascular catheter retention VS Central vascular catheter replacementActive comparator 1 intervention
Group D: Cephalosporin VS Carbapenem for low risk AmpC organismsActive comparator 1 intervention
Group E: Routine follow-up blood culture VS No routine follow-up blood cultureActive comparator 1 intervention

Trial outcomes

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).

Time frame
90 days

Secondary outcomes

1

90-day mortality

Time frame
90 days
2

90-day re-infection

Time frame
90 days
3

90-day all cause readmission

Time frame
90 days
4

90-day AMR colonization/infection

Time frame
90 days

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Sunnybrook Health Sciences Centre

Lead sponsor

Canadian Institutes of Health Research (CIHR)

Collaborator

Clínica Universidad de La Sabana

Collaborator

Universidad de La Sabana, Colombia

Collaborator

Aotearoa Clinical Trials

Collaborator

Source ClinicalTrials.gov
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