BALANCE+ Vanguard Phase

NCT05893147 | Completed DMC

• 1 other identifier: 4369
• Study Type: interventional
• Target: 174
• Locations: 1 country
• Sites: 10

Brief Summary

The goal of the BALANCE+ clinical trial is to transform random care to randomized care for patients with Gram negative bloodstream infections to inform best treatment approaches and optimize outcomes. BALANCE+, a perpetual platform trial, will efficiently answer multiple questions that are important for hospitalized patients with Gram negative bloodstream infections.

Conditions

Gram-negative Bacteremia

Outcome Measures

Primary Outcomes (7)

• Recruitment rate (co-primary outcomes of BALANCE+ vanguard phase)

  Recruitment rate will be measured as the number of patients randomized to each study domain, overall, and by individual participating site. Investigators will target a minimum overall recruitment rate of 1 patient/site/month in the de-escalation domain, beta-lactam versus non-beta-lactam stepdown domain, and FUBC domain; and 0.25 patients/site/month in the line replacement domain.

  1 year

• Protocol adherence (co-primary outcomes of BALANCE+ vanguard phase)

  Protocol adherence will be calculated differently depending on the domain, but in each case will require adherence to the specific intervention arm and complete follow-up for the primary outcome. Investigators will target ≥90% adherence in each arm of each domain.

  1 year

• De-escalation versus no de-escalation domain

  * Patient-centered, ordinal Desirability of Outcome Ranking (DOOR) outcome: (dead at 90 days) \< (alive at 90 days with reinfection and readmission) \< (alive at 90 days with reinfection or readmission) \< (alive at 90 days with neither reinfection nor readmission) * Tie-breaker within ordinal levels: new antimicrobial resistance (AMR) colonization or infection from routine cultures

  90 days

• Oral beta-lactam versus non beta-lactam domain

  * Ordinal DOOR outcome: (dead at 90 days) \< (alive at 90 days with reinfection and readmission) \< (alive at 90 days with reinfection or readmission) \< (alive at 90 days with neither reinfection nor readmission) * Tie-breaker within ordinal levels: new AMR colonization or infection from routine cultures

  90 days

• Central vascular catheter retention versus replacement domain

  * Ordinal DOOR outcome: (dead at 90 days) \< (alive at 90 days with reinfection and readmission) \< (alive at 90 days with reinfection or readmission) \< (alive at 90 days with neither reinfection nor readmission) * No tie-breaker

  90 days

• Low-risk AmpC domain

  * Ordinal DOOR outcome: (dead at 90 days) \< (alive at 90 days with reinfection and readmission) \< (alive at 90 days with reinfection or readmission) \< (alive at 90 days with neither reinfection nor readmission) * Tie-breaker within ordinal levels: new AMR colonization or infection from routine cultures

  90 days

• Follow-up blood culture domain

  * Ordinal DOOR outcome: (dead at 90 days) \< (alive at 90 days with reinfection and readmission) \< (alive at 90 days with reinfection or readmission) \< (alive at 90 days with neither reinfection nor readmission) * No tie-breaker

  90 days

Secondary Outcomes (7)

• 90-day mortality

  90 days

• 90-day reinfection

  90 days

• 90-day all cause readmission

  90 days

• 90-day AMR colonization/infection

  90 days

• 90-day Clostridioides difficile infection (CDI)

  90 days

Study Arms (5)

De-escalation VS No De-escalation

ACTIVE COMPARATOR

Other: De-escalation VS No De-escalation

Oral beta-lactams VS Oral Non-beta-lactams

ACTIVE COMPARATOR

Other: Oral beta-lactams VS non beta-lactams

Central vascular catheter retention VS Central vascular catheter replacement

ACTIVE COMPARATOR

Other: Central vascular catheter retention VS Central vascular catheter replacement

Cephalosporin VS Carbapenem for low risk AmpC organisms

ACTIVE COMPARATOR

Other: Cephalosporin VS Carbapenem for low risk AmpC organisms

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

ACTIVE COMPARATOR

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

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 group: switched to narrower spectrum antibiotic.

De-escalation VS No De-escalation

Oral beta-lactams VS non beta-lactams OTHER

Beta-lactam antibiotic: This can be ciprofloxacin, moxifloxacin, levofloxacin or trimethoprim-sulfamethoxazole. Non beta-lactam antibiotic: This can be, but not limited to, amoxicillin, amoxicillin-clavulanate, cephalexin, cefadroxil, or cefixime.

Oral beta-lactams VS Oral Non-beta-lactams

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 no longer needed.

Central vascular catheter retention VS Central vascular catheter replacement

Cephalosporin VS Carbapenem for low risk AmpC organisms OTHER

Cephalosporin (ceftriaxone) at standard doses Carbapenem (like Meropenem, Ertapenem etc) at standard doses

Cephalosporin VS Carbapenem for low risk AmpC organisms

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

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

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• patient's goals of care are for palliation with no active treatment
• moribund patient, not expected to survive \> 72 hours
• (A) DE-ESCALATION VS. NO DE-ESCALATION DOMAIN
• \. included in BALANCE+ platform
• receiving an empiric antibiotic regimen at the time of blood culture finalization to which the GN pathogen(s) are not sensitive
• carbapenem-resistance (so that patients will not need to remain on reserve-use agents)
• no de-escalation option due to any or all of
• i. resistance ii. allergies iii. medical contraindications iv. drug-interaction risk v. other relevant reason
• patients with a suspected or proven polymicrobial source of infection
• (B) BETA-LACTAM VS. NON-BETA-LACTAM ORAL/ENTERAL TREATMENT DOMAIN
• included in BALANCE+ platform
• initially treated with intravenous antibiotics, but clinical team transitioning patient to oral/enteral antibiotic within 7 days of starting treatment
• enrolled in an arm of another BALANCE+ platform domain which limits the use of oral/enteral therapy
• \- no-de-escalation arm
• no non-beta-lactam options due to any or all of

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (10)

Foothills Hospital

Calgary, Alberta, Canada

Location

Peter Lougheed Centre

Calgary, Alberta, Canada

Location

Eastern Regional Health Authority

St. John's, Newfoundland and Labrador, Canada

Location

The Ottawa Hospital

Ottawa, Ontario, Canada

Location

Niagara Health System

St. Catharines, Ontario, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N3M5, Canada

Location

Michael Garron Hospital

Toronto, Ontario, Canada

Location

Mount Sinai Hospital

Toronto, Ontario, Canada

Location

North York General Hospital

Toronto, Ontario, Canada

Location

University Health Network

Toronto, Ontario, Canada

Location

Related Publications (1)

• Daneman N, Johnstone J, Lee TC, MacFadden DR, McDonald EG, Morpeth SC, Ong SWX, Paterson DL, Pinto RL, Rishu A, Rogers BA, Yahav D, Coburn B, Daley P, Das P, Fiest K, Findlater A, Fralick M, George M, Kandel C, Malavade A, Powis J, Somayaji R, Fowler R; BALANCE+ Investigators, and the Association of Medical Microbiology and Infectious Disease Canada Clinical Research Network and the Canadian Critical Care Trials Group. Assessing the feasibility of a platform trial for Gram negative bloodstream infections: results from the vanguard phase of BALANCE. BMJ Open. 2025 Dec 5;15(12):e101588. doi: 10.1136/bmjopen-2025-101588.

  PMID: 41360461 DERIVED

Study Officials

• Nick Daneman, MD

  Sunnybrook Health Sciences Centre

  PRINCIPAL INVESTIGATOR

• Rob Fowler, MD

  Sunnybrook Health Sciences Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 72 in the overall platform AND at least 12 in each domain.

Study Record Dates

• First Submitted: May 18, 2023
• First Posted: June 7, 2023
• Study Start: August 26, 2023
• Primary Completion: July 23, 2024
• Study Completion: August 10, 2024
• Last Updated: October 1, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

CA (10)