A Platform Trial for Gram Negative Bloodstream Infections

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.

Conditions

• Gram-negative Bacteremia

Interventions

OTHER

De-escalation VS No De-escalation

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).

OTHER

Oral beta-lactams VS non beta-lactams

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.

OTHER

Central vascular catheter retention VS Central vascular catheter replacement

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.

OTHER

Cephalosporin VS Carbapenem for low risk AmpC organisms

Cephalosporin (ceftriaxone) at standard doses Carbapenem (Meropenem or Ertapenem) at standard doses

OTHER

Routine follow-up blood culture VS No routine follow-up blood culture

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

Sponsors & Collaborators

• Canadian Institutes of Health Research (CIHR)

  collaborator OTHER_GOV

• Clínica Universidad de La Sabana

  collaborator UNKNOWN

• Universidad de La Sabana, Colombia

  collaborator UNKNOWN

• Aotearoa Clinical Trials

  collaborator UNKNOWN

• Sunnybrook Health Sciences Centre

  lead OTHER

Principal Investigators

• Nick Daneman, MD · Sunnybrook Health Sciences Centre

• Rob Fowler, MD · Sunnybrook Health Sciences Centre

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

0 Years

Max Age

130 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-04-24

Primary Completion

2027-04-30

Completion

2028-04-30

Countries

• Australia
• Canada
• Colombia
• Israel
• New Zealand

Study Locations