BALANCE+ Vanguard Phase

Not Applicable

Completed

• Conditions: Gram-negative Bacteremia
• Interventions: Other: De-escalation VS No De-escalation; Other: Oral beta-lactams VS non beta-lactams; Other: Routine follow-up blood culture VS No routine follow-up blood culture; Other: Central vascular catheter retention VS Central vascular catheter replacement; Other: Cephalosporin VS Carbapenem for low risk AmpC organisms

• Registration Number: NCT05893147
• Lead Sponsor: Sunnybrook Health Sciences Centre

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.

Detailed Description

Bloodstream infections (BSIs) are common and lethal, ranking among the top 7 causes of death, with 600,000 cases and 90,000 deaths per year in North America, and 1.2 Million cases and 150,000 deaths per year in Europe. Despite being a leading cause of death worldwide, bloodstream infections remain understudied. Treatment approaches are complicated by rising rates of antimicrobial resistance and declining new drug development.

BALANCE+ provides a platform upon which to answer multiple pressing cross-cutting questions for patients with Gram negative bloodstream infections, including the concept of de-escalating antibiotic spectrum, optimal transition to oral antibiotics, and the role for routine follow up blood culture testing. The trial will also include a syndrome-specific question of whether to remove or retain a central vascular catheter, and a pathogen-specific question of whether cephalosporins are sufficient for patients with low-risk AmpC organisms. As each question is answered, optimal therapies will be adopted into usual care, and new questions will be introduced into the platform of the trial. The evidence generated by BALANCE+ will improve cure for this vulnerable patient population.

Study Timeline

• Study First Submitted: 2023-05-18
• Study First Submitted QC: 2023-05-30
• Study First Posted: 2023-06-07
• Study Start: 2023-08-26
• Primary Completion: 2024-07-23
• Study Completion: 2024-08-10
• Status Verified: 2024-09
• Last Update Submitted: 2024-09-26
• Last Update Posted: 2024-09-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 174

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
De-escalation VS No De-escalation	De-escalation VS No De-escalation	-
Oral beta-lactams VS Oral Non-beta-lactams	Oral beta-lactams VS non beta-lactams	-
Routine follow-up blood culture VS No routine follow-up blood culture	Routine follow-up blood culture VS No routine follow-up blood culture	-
Central vascular catheter retention VS Central vascular catheter replacement	Central vascular catheter retention VS Central vascular catheter replacement	-
Cephalosporin VS Carbapenem for low risk AmpC organisms	Cephalosporin VS Carbapenem for low risk AmpC organisms	-

Primary Outcome Measures

Name	Time	Method
Recruitment rate (co-primary outcomes of BALANCE+ vanguard phase)	1 year	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.
De-escalation versus no de-escalation domain	90 days	* 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
Oral beta-lactam versus non beta-lactam domain	90 days	* 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
Central vascular catheter retention versus replacement domain	90 days	* 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
Low-risk AmpC domain	90 days	* 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
Protocol adherence (co-primary outcomes of BALANCE+ vanguard phase)	1 year	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.
Follow-up blood culture domain	90 days	* 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

Secondary Outcome Measures

Name	Time	Method
60-day mortality	60 days
90-day reinfection	90 days
90-day Clostridioides difficile infection (CDI)	90 days
30-day mortality	30 days
90-day AMR colonization/infection	90 days
90-day mortality	90 days
90-day all cause readmission	90 days

Trial Locations

Locations (10)

Foothills Hospital; 🇨🇦 Calgary, Alberta, Canada

Peter Lougheed Centre; 🇨🇦 Calgary, Alberta, Canada

Eastern Regional Health Authority; 🇨🇦 Saint John's, Newfoundland and Labrador, Canada

The Ottawa Hospital; 🇨🇦 Ottawa, Ontario, Canada

Niagara Health System; 🇨🇦 St. Catharines, Ontario, Canada

Sunnybrook Health Sciences Centre; 🇨🇦 Toronto, Ontario, Canada

Michael Garron Hospital; 🇨🇦 Toronto, Ontario, Canada

Mount Sinai Hospital; 🇨🇦 Toronto, Ontario, Canada

North York General Hospital; 🇨🇦 Toronto, Ontario, Canada

University Health Network; 🇨🇦 Toronto, Ontario, Canada