An interventional study of De-escalation VS No De-escalation and Oral beta-lactams VS non beta-lactams in Gram-negative Bacteremia, sponsored by Sunnybrook Health Sciences Centre. Completed at 10 sites in Canada. Per ClinicalTrials.gov, last updated 2024-10-01.
Sponsored by Sunnybrook Health Sciences Centre · Not applicable, Interventional, and Other
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.
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.
Sunnybrook Health Sciences Centre is the lead sponsor of 582 studies on the registry; 133 are open to participants now.
Of its 6 completed or terminated interventional studies of FDA-regulated products, 2 (33%) have results posted.
Counted across the registry records on this site, refreshed daily.
PLATFORM INCLUSION CRITERIA
PLATFORM EXCLUSION CRITERIA
DOMAIN SPECIFIC INCLUSION AND EXCLUSION CRITERIA
(A) DE-ESCALATION VS. NO DE-ESCALATION DOMAIN
Inclusion Criteria
1. included in BALANCE+ platform
Exclusion Criteria
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
(B) BETA-LACTAM VS. NON-BETA-LACTAM ORAL/ENTERAL TREATMENT DOMAIN
Inclusion Criteria
Exclusion Criteria
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
i. resistance ii. allergies iii. medical contraindications iv. drug-interaction risk v. other relevant reason
no beta-lactam options due to any or all of
i. resistance ii. allergies iii. medical contraindications iv. drug-drug interaction risk v. other relevant reason
(C) CENTRAL VASCULAR CATHETER REPLACEMENT DOMAIN
Inclusion Criteria
Exclusion Criteria
patient has definite indication for central vascular catheter removal
(D) LOW-RISK AmpC DOMAIN
Inclusion Criteria
positive blood culture with GN bacterium, of the following species
Exclusion Criteria
(E) FOLLOW UP BLOOD CULTURE DOMAIN
Inclusion Criteria
1. included in BALANCE+ platform
Exclusion Criteria
definite indication for repeat blood culture testing
Other: De-escalation VS No De-escalation
Other: Oral beta-lactams VS non beta-lactams
Other: Central vascular catheter retention VS Central vascular catheter replacement
Other: Cephalosporin VS Carbapenem for low risk AmpC organisms
Other: Routine follow-up blood culture VS No routine follow-up blood culture
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.
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.
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.
Cephalosporin (ceftriaxone) at standard doses Carbapenem (like Meropenem, Ertapenem etc) at standard doses
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
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.
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 90 days
90-day mortality
Time frame: 90 days
90-day reinfection
Time frame: 90 days
90-day all cause readmission
Time frame: 90 days
90-day AMR colonization/infection
Time frame: 90 days
90-day Clostridioides difficile infection (CDI)
Time frame: 90 days
30-day mortality
Time frame: 30 days
60-day mortality
Time frame: 60 days
Plan to share: No
This study is completed, as verified in Sep 2024. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Sunnybrook Health Sciences Centre →