Recruiting

Observational Study

Sponsor:

Sunnybrook Health Sciences Centre

Code:

NCT06537609

Conditions

Gram-negative Bacteremia

Eligibility Criteria

Sex: All

Age: 0 - 70+

Healthy Volunteers: Not accepted

Interventions

De-escalation VS No De-escalation

Oral beta-lactams VS non beta-lactams

Central vascular catheter retention VS Central vascular catheter replacement

Cephalosporin VS Carbapenem for low risk AmpC organisms

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

Study Details

Brief 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

Study ID

NCT06537609

Start date

Apr 24, 2024

Status verified date

Sep, 2026

Completion date

Apr, 2028

Anticipated

Primary completion date

Apr, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 0 - 70+

Healthy Volunteers: Not accepted

PLATFORM INCLUSION 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
  • previously enrolled in the platform trial
  • not eligible for any domain at the time of screening

DOMAIN SPECIFIC INCLUSION AND EXCLUSION CRITERIA

1. De-escalation versus no de-escalation domain

Inclusion Criteria

\- 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
  • arbapenem-non-susceptible
  • no de-escalation option due to any or all of:

  • antimicrobial resistance
  • allergies
  • medical contraindications
  • drug-drug interaction risk
  • other relevant reason
  • patients with a suspected or proven polymicrobial source of infection
  • > 24 hours since index blood culture susceptibility results finalization
2. Beta-lactam versus 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 (patients in the no de-escalation arm cannot be randomized into this domain unless they are ready for discharge home, in which case de-escalation is allowable to oral agents at discharge)
  • no non-beta-lactam options due to any or all of:

  • resistance
  • allergies
  • medical contraindications
  • drug-interaction risk
  • other relevant reason
  • no beta-lactam options due to any or all of:

  • resistance
  • allergies
  • medical contraindications
  • drug-interaction risk
  • other relevant reason
  • pregnancy
  • already received >24 hours of oral antibiotics after index blood culture finalization
3. Central vascular catheter replacement domain

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
  • ongoing septic shock with definite/probable line source

  • concomitant S. aureus bacteremia
  • concomitant candidemia
  • 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)
4. Low-risk AmpC domain

Inclusion Criteria
  • included in BALANCE+ platform
  • positive blood culture with GN bacterium, of the following species: i. Serratia spp. ii Morganella spp. iii Providencia spp. iv Proteus spp. other than P.mirabilis
  • organism is susceptible to ceftriaxone

Exclusion Criteria
  • severe allergy to beta-lactams (e.g., type 4 hypersensitivity reaction or DRESS)
  • baseline phenotypic non-susceptiblity to ceftriaxone
  • more than 1 calendar day beyond availability of susceptibility results
5. Follow up blood culture domain

Inclusion Criteria

\- included in BALANCE+ platform

Exclusion Criteria

  • patient died or discharged from hospital prior to day 4
  • blood culture already collected by the treating team at day 4±1
  • >5 days since index positive blood culture collection
  • definite indication for repeat blood culture testing

  • concomitant S. aureus bacteremia
  • concomitant Candidemia
  • clinical suspicion for infective endocarditis

Study Design

Enrollment

2500 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: De-escalation VS No De-escalation

active comparator: Oral beta-lactams VS Oral Non-beta-lactams

active comparator: Central vascular catheter retention VS Central vascular catheter replacement

active comparator: Cephalosporin VS Carbapenem for low risk AmpC organisms

active comparator: Routine follow-up blood culture VS No routine follow-up blood culture

Enrollment to the domain has been completed.

Interventions

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).

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.

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.

Cephalosporin VS Carbapenem for low risk AmpC organisms

Cephalosporin (ceftriaxone) at standard doses

Carbapenem (Meropenem or Ertapenem) at standard doses

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

Primary outcome measure

  • Desirability of Outcome Ranking (DOOR) Ordinal Scale which incorporates death, reinfection, readmission, and for some domains incorporates a tie-breaker of new antimicrobial resistance (AMR). [ Time Frame: 90 days ]

Central Contacts and Locations

Central contacts

Nick Daneman, MD

4164806100nick.daneman@sunnybrook.ca

Mithun Mohan George

416-480-6100mithun.george@sri.utoronto.ca

Locations

Foothills Hospital

Recruiting

Calgary, Alberta, Canada

Peter Lougheed Centre

Recruiting

Calgary, Alberta, Canada

Contacts

Ranjani Somayaji

(403) 943-4555rsomayaj@ucalgary.ca

Principal Investigator:

Ranjani Somayaji

Rockyview General Hospital

Recruiting

Calgary, Alberta, Canada

Contacts

Ranjani Somayaji

(403) 943-3000rsomayaj@ucalgary.ca;kmfiest@ucalgary.ca

Principal Investigator:

Ranjani Somayaji

South Health Campus

Recruiting

Calgary, Alberta, Canada

Contacts

Ranjani Somayaji

(403) 956-1111rsomayaj@ucalgary.ca

Principal Investigator:

Ranjani Somayaji

University of Alberta

Recruiting

Edmonton, Alberta, Canada

Contacts

Wendy Sligl

(780) 492-3111wsligl@ualberta.ca

Principal Investigator:

Wendy Sligl

Surrey Memorial Hospital

Recruiting

Surrey, British Columbia, Canada

Contacts

Kevin Afra

(604) 581-2211Kevin.Afra@fraserhealth.ca

Principal Investigator:

Kevin Afra

Vancouver General Hospital

Recruiting

Vancouver, British Columbia, Canada

Contacts

Jennifer Grant

(604) 875-4111Jennifer.grant@bccdc.ca

Principal Investigator:

Jennifer Grant

Grace Hospital

Recruiting

Winnipeg, Manitoba, Canada

Contacts

Gloria Vazquez-Grande

(204) 837-0111Gloria.Vazquez-Grande@umanitoba.ca

Principal Investigator:

Gloria Vazquez-Grande

Health Sciences Centre

Recruiting

Winnipeg, Manitoba, Canada

Contacts

Sylvain Lother

(204) 787-3661Sylvain.Lother@umanitoba.ca

Principal Investigator:

Sylvain Lother

St. Boniface Hospital

Recruiting

Winnipeg, Manitoba, Canada

Contacts

Terry Wuerz

(204) 233-8563twuerz@hsc.mb.ca

Principal Investigator:

Terry Wuerz

Dr. Everett Chalmers Regional Hospital

Recruiting

Fredericton, New Brunswick, Canada

Contacts

Rosa Rossana

(506) 452-5400Rossana.Rosa@HorizonNB.ca

Principal Investigator:

Rosa Rossana

Eastern Regional Health Authority

Recruiting

St. John's, Newfoundland and Labrador, Canada

Trillium Health Partners - Mississauga Hospital

Recruiting

Mississauga, Ontario, Canada

Contacts

Christopher Graham

(905) 848-7100Christopher.Graham@thp.ca

Principal Investigator:

Christopher Graham

Humber River Health system

Recruiting

North York, Ontario, Canada

Contacts

Ian Brasg

(416) 242-1000ibrasg@hrh.ca

Principal Investigator:

Ian Brasg

North York General Hospital

Recruiting

North York, Ontario, Canada

Contacts

Pavani Das

(416) 756-6000Pavani.Das@nygh.on.ca

Principal Investigator:

Pavani Das

The Ottawa Hospital

Recruiting

Ottawa, Ontario, Canada

Niagara Health System

Recruiting

St. Catharines, Ontario, Canada

Sunnybrook Health Sciences Centre

Recruiting

Toronto, Ontario, Canada, M4N3M5

Contacts

Nick Daneman, MD

4164806100nick.daneman@sunnybrook.ca

Archana Malavade

416-480-6100archana.malavade@sri.utoronto.ca

Principal Investigator:

Rob A Fowler, MD

Michael Garron Hospital

Recruiting

Toronto, Ontario, Canada

Mount Sinai Hospital

Recruiting

Toronto, Ontario, Canada

St. Joseph's Health Centre

Recruiting

Toronto, Ontario, Canada

Contacts

Kevin Schwartz

(416) 530-6000Kevin.Schwartz@unityhealth.to

Principal Investigator:

Kevin Schwartz

University Health Network

Recruiting

Toronto, Ontario, Canada

CHU de Québec - Université Laval

Recruiting

Laval, Quebec, Canada

Contacts

Francois Lauzier

(418) 525-4444francois.lauzier@fmed.ulaval.ca

Principal Investigator:

Francois Lauzier

Hôpital de la Cité de la Santé

Recruiting

Laval, Quebec, Canada

Contacts

Marco Bergevin

450- 668-1010Marco-Andres.Bergevin.med@ssss.gouv.qc.ca

Principal Investigator:

Marco Bergevin

Montreal General Hospital- McGill

Recruiting

Montreal, Quebec, Canada

Contacts

Todd C Lee

(514) 934-1934todd.lee@mcgill.ca

Principal Investigator:

Emily Mcdonald

Royal Victoria Hospital- McGill

Recruiting

Montreal, Quebec, Canada

Contacts

Todd C Lee

(514) 934-1934todd.lee@mcgill.ca

Principal Investigator:

Emily McDonald

Université de Sherbrooke

Recruiting

Sherbrooke, Quebec, Canada

Centre hospitalier affilié universitaire régional (CHAUR)

Recruiting

Trois-Rivières, Quebec, Canada, G8Z 3R9

Contacts

Jean-François Naud

(819) 697-3333jean-francois.naud.med@ssss.gouv.qc.ca

Principal Investigator:

Jean-François Naud

More Information

Sponsor

Sunnybrook Health Sciences Centre

Last update posted

Sep 4, 2026

Last verified

Sep, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Sunnybrook Health Sciences Centre on 2026-09-04.