BALANCE+ Vanguard Phase | NCT05893147

NCT05893147

Status Module

Name	Class
Canadian Institutes of Health Research (CIHR)	OTHER_GOV

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
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.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

Measure	Description	Time Frame
90-day mortality		90 days
90-day reinfection		90 days
90-day all cause readmission

Eligibility Module

Eligibility Criteria

PLATFORM INCLUSION CRITERIA

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

PLATFORM EXCLUSION CRITERIA

patient's goals of care are for palliation with no active treatment
moribund patient, not expected to survive > 72 hours

DOMAIN SPECIFIC INCLUSION AND EXCLUSION CRITERIA

(A) DE-ESCALATION VS. NO DE-ESCALATION DOMAIN

Inclusion Criteria

1. included in BALANCE+ platform

Exclusion Criteria

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

Inclusion Criteria

included in BALANCE+ platform
initially treated with intravenous antibiotics, but clinical team transitioning patient to oral/enteral antibiotic within 7 days of starting treatment

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

Inclusion Criteria

included in BALANCE+ platform
has an indwelling central vascular catheter that was already in place within the 48-hour period before the onset of bloodstream infection (i.e. is not a new catheter placed within 48 hours of the onset of infection)

Exclusion Criteria

patient has no ongoing need for a central vascular catheter
patient has definite indication for central vascular catheter removal
1. ongoing septic shock with definite/probable line source
2. concomitant S. aureus bacteremia
3. concomitant candidemia
4. local suppurative signs (severe redness, warmth, pain, swelling or fluctuance/collection) necessitating catheter removal, or other clinical evidence of infected line (e.g. imaging/echocardiographic findings)
5. definite alternative source of GN BSI

(D) LOW-RISK AmpC DOMAIN

Inclusion Criteria

included in BALANCE+ platform
positive blood culture with GN bacterium, of the following species
1. Serratia spp.
2. Morganella spp.
3. Providencia spp.
4. Proteus spp. other than P.mirabilis
5. organism is sensitive to ceftriaxone

Exclusion Criteria

severe allergy to beta-lactams (eg, type 4 hypersensitivity reaction or DRESS)
baseline phenotypic resistance to ceftriaxone

(E) FOLLOW UP BLOOD CULTURE DOMAIN

Inclusion Criteria

1. included in BALANCE+ platform

Exclusion Criteria

patient already discharged home prior to day 4
definite indication for repeat blood culture testing
1. concomitant Staph. aureus bacteremia
2. concomitant Candidemia
3. clinical suspicion for infective endocarditis (e.g., presence of prosthetic valve, implantable cardiac device)

Name	Affiliation	Role
Nick Daneman, MD	Sunnybrook Health Sciences Centre	Principal Investigator
Rob Fowler, MD	Sunnybrook Health Sciences Centre	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Foothills Hospital		Calgary	Alberta		Canada
Peter Lougheed Centre