Gram-negative BacteremiaBALANCE+NCT06537609
A Platform Trial for Gram Negative Bloodstream Infections
A study testing De-escalation VS No De-escalation, Oral beta-lactams VS non beta-lactams and Central vascular catheter retention VS Central vascular catheter replacement in people with Gram-negative Bacteremia, run by Sunnybrook Health Sciences Centre at 39 sites in 5 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 0 to 130 years
- Conditions the study is for
- Gram-negative Bacteremia
- What is being tested?
- De-escalation VS No De-escalation, Oral beta-lactams VS non beta-lactams and Central vascular catheter retention VS Central vascular catheter replacement
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,500 participants
- Where
- 39 sitesin 5 countries
- Study dates
- 24 Apr 2024to Apr 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 to 130 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- included in BALANCE+ platform
- included in BALANCE+ platform
- initially treated with intravenous antibiotics, but clinical team transitioning patient to oral/enteral antibiotic within 7 days of starting treatment
- 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)
- included in BALANCE+ platform
Show all 9Show fewer
- 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
- included in BALANCE+ platform
Who cannot join
- 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
Show all 46Show fewer
- 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
- Beta-lactam versus non-beta-lactam oral/enteral treatment domain
- 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
- Central vascular catheter replacement domain
- 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)
- Low-risk AmpC domain
- 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
- Follow up blood culture domain
- 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
Trial locations and contacts
39 sites in 5 countries. Contact the study team or a site near you to ask about taking part.
39 sites in 5 countries
Canada28 sites, 28 recruiting
- Recruiting
Foothills Hospital
Calgary, Alberta
Ranjani Somayaji, MD
- Recruiting
Peter Lougheed Centre
Calgary, Alberta
Ranjani Somayaji, (403) 943-4555, rsomayaj@ucalgary.ca
Ranjani Somayaji
- Recruiting
Rockyview General Hospital
Calgary, Alberta
Ranjani Somayaji, (403) 943-3000, rsomayaj@ucalgary.ca;kmfiest@ucalgary.ca
Ranjani Somayaji
- Recruiting
South Health Campus
Calgary, Alberta
Ranjani Somayaji, (403) 956-1111, rsomayaj@ucalgary.ca
Ranjani Somayaji
- Recruiting
University of Alberta
Edmonton, Alberta
Wendy Sligl, (780) 492-3111, wsligl@ualberta.ca
Wendy Sligl
- Recruiting
Dr. Everett Chalmers Regional Hospital
Fredericton, New Brunswick
Rosa Rossana, (506) 452-5400, Rossana.Rosa@HorizonNB.ca
Rosa Rossana
- Recruiting
CHU de Québec - Université Laval
Laval, Quebec
Francois Lauzier, (418) 525-4444, francois.lauzier@fmed.ulaval.ca
Francois Lauzier
- Recruiting
Hôpital de la Cité de la Santé
Laval, Quebec
Marco Bergevin, 450- 668-1010, Marco-Andres.Bergevin.med@ssss.gouv.qc.ca
Marco Bergevin
- Recruiting
Trillium Health Partners - Mississauga Hospital
Mississauga, Ontario
Christopher Graham, (905) 848-7100, Christopher.Graham@thp.ca
Mobina Khurram
- Recruiting
Montreal General Hospital- McGill
Montreal, Quebec
Todd C Lee, (514) 934-1934, todd.lee@mcgill.ca
Emily Mcdonald
- Recruiting
Royal Victoria Hospital- McGill
Montreal, Quebec
Todd C Lee, (514) 934-1934, todd.lee@mcgill.ca
Emily McDonald
- Recruiting
Humber River Health system
North York, Ontario
Ian Brasg, (416) 242-1000, ibrasg@hrh.ca
Ian Brasg
- Recruiting
North York General Hospital
North York, Ontario
Pavani Das, (416) 756-6000, Pavani.Das@nygh.on.ca
Pavani Das
- Recruiting
The Ottawa Hospital
Ottawa, Ontario
Derek McFadden, MD
- Recruiting
Université de Sherbrooke
Sherbrooke, Quebec
François Lamontagne, MD
- Recruiting
Niagara Health System
St. Catharines, Ontario
Aidan Findlater, MD
- Recruiting
Eastern Regional Health Authority
St. John's, Newfoundland and Labrador
Peter Daley, MD
- Recruiting
Surrey Memorial Hospital
Surrey, British Columbia
Kevin Afra, (604) 581-2211, Kevin.Afra@fraserhealth.ca
Kevin Afra
- Recruiting
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N3M5
Nick Daneman, MD, 4164806100 ext. 2791, nick.daneman@sunnybrook.ca
Archana Malavade, 416-480-6100 ext. 688153, archana.malavade@sri.utoronto.ca
- Recruiting
Michael Garron Hospital
Toronto, Ontario
Christopher Kandel, MD
- Recruiting
Mount Sinai Hospital
Toronto, Ontario
Michael Fralick, PhD
- Recruiting
St. Joseph's Health Centre
Toronto, Ontario
Kevin Schwartz, (416) 530-6000, Kevin.Schwartz@unityhealth.to
Kevin Schwartz
- Recruiting
University Health Network
Toronto, Ontario
Bryan Coburn, MD
- Recruiting
Centre hospitalier affilié universitaire régional (CHAUR)
Trois-Rivières, Quebec, G8Z 3R9
Jean-François Naud, (819) 697-3333, jean-francois.naud.med@ssss.gouv.qc.ca
Jean-François Naud
- Recruiting
Vancouver General Hospital
Vancouver, British Columbia
Jennifer Grant, (604) 875-4111, Jennifer.grant@bccdc.ca
Jennifer Grant
- Recruiting
Grace Hospital
Winnipeg, Manitoba
Gloria Vazquez-Grande, (204) 837-0111, Gloria.Vazquez-Grande@umanitoba.ca
Gloria Vazquez-Grande
- Recruiting
Health Sciences Centre
Winnipeg, Manitoba
Sylvain Lother, (204) 787-3661, Sylvain.Lother@umanitoba.ca
Sylvain Lother
- Recruiting
St. Boniface Hospital
Winnipeg, Manitoba
Terry Wuerz, (204) 233-8563, twuerz@hsc.mb.ca
Terry Wuerz
Australia8 sites, 8 recruiting
- Recruiting
Monash Medical Center
Clayton, Victoria
Ben Rogers, (03) 9594 6666, Ben.Rogers@monash.edu
Ben Rogers
- Recruiting
Royal Brisbane and Women's Hospital
Herston, Queensland, 4006
Patrick Harris, Infectious Disease Physician, +61 7 3646 8111, patrick.harris2@health.qld.gov.au
Patrick Harris, Infectious Disease Physician
- Recruiting
St George Hospital
Kogarah, New South Wales, 2217
Richard Sullivan, +61 2 9113 1111, richard.sullivan@health.nsw.gov.au
Rachael Roberts, Research Coordinator
- Recruiting
Fiona Stanley Hospital
Murdoch, Western Australia
Edward Raby, +61 8 6152 2222, Edward.Raby@health.wa.gov.au
Edward Raby
- Recruiting
St John of God
Murdoch, Western Australia
Adrian Regli, +61 8 9438 9000, adrian.regli@gmail.com
Adrian Regli
- Recruiting
John Hunter Hospital
New Lambton, New South Wales
Joshua Davis, Joshua.Davis@health.nsw.gov.au
+61 2 4921 3000
- Recruiting
Redcliffe Hospital
Redcliffe, Queensland
Kevin O'Callaghan, +61 7 3883 7777, Kevin.OCallaghan@health.qld.gov.au
Kevin O'Callaghan
- Recruiting
Sunshine Coast University Hospital
Sunshine Coast, Queensland
Gururaj Nagaraj, +61 7 5202 0000, gururaj.nagaraj@health.oqld.gov.au
Gururaj Nagaraj
Colombia1 site, 1 recruiting
- Recruiting
Universidad de La Sabana
Chía, Cundinamarca
Luis Felipe Reyes Velasco, +57 601 8615555, luis.reyes5@unisabana.edu.co
Luis Felipe Reyes Velasco
Israel1 site, 1 recruiting
- Recruiting
Sheba Medical Center
Ramat Gan, Tel Aviv
Dafna Yahav, +972 3-530-3030, dafna.yahav@gmail.com
Dafna Yahav
New Zealand1 site, 1 recruiting
- Recruiting
Middlemore Hospital
Auckland, Auckland, 2025
Susan Morpeth, Clinical Microbiologist, +64 9 2709758, Susan.Morpeth@middlemore.co.nz
Aotearoa Clinical Trials, +64 9 2709758, grants@aotearoatrials.nz
About this study
Official title: BALANCE+: A Platform Trial for Gram Negative Bloodstream Infections
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.
Read the detailed description
BALANCE+ is an adaptive platform trial evaluating multiple treatment options in patients admitted to the hospital due to Gram negative bloodstream infections (BSIs). It focuses on both cross-cutting and subgroup-specific questions, using an open-label, pragmatic design embedded in routine care.
BALANCE+ addresses the significant health concern of BSIs, which have high morbidity and mortality rates, exacerbated by the global public health threat of antimicrobial resistance (AMR). With rising resistance rates and limited new drug development, effective treatment strategies for BSIs remain under-researched.
BALANCE+ follows the BALANCE trial, which evaluated duration of antibiotic treatment, and aims to further investigate critical questions in managing Gram-negative BSIs. This platform trial will explore various aspects of BSI treatment, including antibiotic de-escalation, oral antibiotic choices, central line management, treatment of specific pathogens, and the necessity of follow-up blood cultures.
BALANCE+ is using Bayesian methods without a fixed sample size. Interim analyses will occur after every 1000th patient in each domain, and then for every 200th patient thereafter. The trial will stop if futility or superiority thresholds are met, or if a domain reaches its ceiling sample size (2500 patients for most domains and 4000 for the beta-lactam versus non-beta-lactam domain) without meeting a stopping threshold.
A vanguard pilot trial involving over 150 patients at 9 hospitals across Canada confirmed the feasibility of the BALANCE+ trial. The main trial will include patients from the vanguard pilot phase since there has been no major change in the overall study design and domains. The adaptive design allows for interim analyses and adjustments by adding or removing domains as per the statistical analysis plan, enhancing the trial's efficiency and relevance.
- Conditions
- Gram-negative Bacteremia
- Being tested
- 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
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
De-escalation VS No De-escalationOther
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-lactamsOther
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 replacementOther
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 organismsOther
Cephalosporin (ceftriaxone) at standard doses
Carbapenem (Meropenem or Ertapenem) at standard doses
Routine follow-up blood culture VS No routine follow-up blood cultureOther
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
| Study group | Role | What they receive |
|---|---|---|
| De-escalation VS No De-escalation | Active comparator | Not described Receives: Other: De-escalation VS No De-escalation |
| Oral beta-lactams VS Oral Non-beta-lactams | Active comparator | Not described Receives: Other: Oral beta-lactams VS non beta-lactams |
| Central vascular catheter retention VS Central vascular catheter replacement | Active comparator | Not described Receives: Other: Central vascular catheter retention VS Central vascular catheter replacement |
| Cephalosporin VS Carbapenem for low risk AmpC organisms | Active comparator | Not described Receives: Other: Cephalosporin VS Carbapenem for low risk AmpC organisms |
| Routine follow-up blood culture VS No routine follow-up blood culture | Active comparator | Enrollment to the domain has been completed. Receives: Other: Routine follow-up blood culture VS No routine follow-up blood culture |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
The primary outcome for each domain will use a Desirability of Outcome Ranking (DOOR) ordinal scale in which patients are categorized into the following mutually exclusive categories, ranked from best to worst status:
- Alive with no reinfection or readmission.
- Alive with reinfection OR readmission.
- Alive with reinfection AND readmission.
- Dead
For the 3 antibiotic-related domains (the de-escalation versus no de-escalation domain, the beta-lactam versus non-beta-lactam domain, and the low risk AmpC domain) there will be an additional tie-breaker within ordinal levels 1, 2 and 3 based on whether there was new detection of antimicrobial resistance (AMR).
Measured: 90 days
Secondary outcomes (8)
90-day mortality
Measured: 90 days
90-day re-infection
Measured: 90 days
90-day all cause readmission
Measured: 90 days
90-day AMR colonization/infection
Measured: 90 days
90-day Clostridioides difficile infection (CDI)
Measured: 90 days
30-day mortality
Measured: 30 days
60-day mortality
Measured: 60 days
Additional Secondary Outcomes for Individual Domains
(i) De-escalation versus no de-escalation
- change in total microbiome diversity between the day of randomization and discharge (or day 30 if earlier)
- net change in resistome AMR burden between the day of randomization and discharge (or day 30 if earlier). (ii) Beta-lactam versus non-beta-lactam
- antibiotic-related allergic reaction
- antibiotic-related adverse event (iii) Central vascular catheter replacement versus retention
- pneumothorax or thoracotomy tube insertion related to vascular catheter
- clinically important bleeding
- line associated thrombus
- persistent bacteremia >5d from initial index culture
- secondary bloodstream infection with new bacterial or fungal organism (iv) Low-risk AmpC
- isolation of ESBL producing organism or third generation cephalosporin resistant Gram negative organism
- isolation of a carbapenem-resistant organism (v) Follow up blood culture domain
- total duration of antibiotic therapy
- hospital length of stay
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2024
- Study start24 Apr 2024
- Primary completionApr 2027 (estimated)
- Study completionApr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gram-negative BacteremiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2,500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sunnybrook Health Sciences Centre
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Clínica Universidad de La Sabana, Universidad de La Sabana, Colombia, Aotearoa Clinical Trials
- Responsible party
- Principal investigator, Dr. Nick Daneman, Sunnybrook Health Sciences Centre
- Investigators
- Nick Daneman, MD, Principal investigator, Sunnybrook Health Sciences CentreRob Fowler, MD, Principal investigator, Sunnybrook Health Sciences Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06537609
- Sponsor's protocol ID
- 4369-1
- Acronym
- BALANCE+
- Status last verified
- Sep 2026
- First submitted
- 25 Jul 2024
- Last updated
- 4 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- BALANCE+: A Platform Trial for Gram Negative Bloodstream Infections
- ClinicalTrials.gov ID
- NCT06537609
- Acronym / sponsor ID
- BALANCE+ / 4369-1
- Conditions
- Gram-negative Bacteremia
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 2,500 participants (estimated)
- Lead sponsor
- Sunnybrook Health Sciences CentreUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Clínica Universidad de La Sabana, Universidad de La Sabana, Colombia, Aotearoa Clinical Trials
- Study start
- 24 Apr 2024 (actual)
- Primary completion
- Apr 2027 (estimated)
- Study completion
- Apr 2028 (estimated)
- First posted
- 5 Aug 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
BALANCE+ is an adaptive platform trial evaluating multiple treatment options in patients admitted to the hospital due to Gram negative bloodstream infections (BSIs). It focuses on both cross-cutting and subgroup-specific questions, using an open-label, pragmatic design embedded in routine care.
BALANCE+ addresses the significant health concern of BSIs, which have high morbidity and mortality rates, exacerbated by the global public health threat of antimicrobial resistance (AMR). With rising resistance rates and limited new drug development, effective treatment strategies for BSIs remain under-researched.
BALANCE+ follows the BALANCE trial, which evaluated duration of antibiotic treatment, and aims to further investigate critical questions in managing Gram-negative BSIs. This platform trial will explore various aspects of BSI treatment, including antibiotic de-escalation, oral antibiotic choices, central line management, treatment of specific pathogens, and the necessity of follow-up blood cultures.
BALANCE+ is using Bayesian methods without a fixed sample size. Interim analyses will occur after every 1000th patient in each domain, and then for every 200th patient thereafter. The trial will stop if futility or superiority thresholds are met, or if a domain reaches its ceiling sample size (2500 patients for most domains and 4000 for the beta-lactam versus non-beta-lactam domain) without meeting a stopping threshold.
A vanguard pilot trial involving over 150 patients at 9 hospitals across Canada confirmed the feasibility of the BALANCE+ trial. The main trial will include patients from the vanguard pilot phase since there has been no major change in the overall study design and domains. The adaptive design allows for interim analyses and adjustments by adding or removing domains as per the statistical analysis plan, enhancing the trial's efficiency and relevance.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| 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 cultureEnrollment to the domain has been completed. |
Who may qualify
- Ages
- 0 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- included in BALANCE+ platform
Key exclusion criteria (46 listed)
- Beta-lactam versus non-beta-lactam oral/enteral treatment domain
- Central vascular catheter replacement domain
- Low-risk AmpC domain
- Follow up blood culture domain
- patient died or discharged from hospital prior to day 4
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| De-escalation VS No De-escalationNo 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). | Other | De-escalation VS No De-escalation |
| Oral beta-lactams VS non beta-lactamsBeta-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. | Other | Oral beta-lactams VS Oral Non-beta-lactams |
| Central vascular catheter retention VS Central vascular catheter replacementCentral 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. | Other | Central vascular catheter retention VS Central vascular catheter replacement |
| Cephalosporin VS Carbapenem for low risk AmpC organismsCephalosporin (ceftriaxone) at standard doses Carbapenem (Meropenem or Ertapenem) at standard doses | Other | Cephalosporin VS Carbapenem for low risk AmpC organisms |
| Routine follow-up blood culture VS No routine follow-up blood cultureRoutine 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 | Other | Routine follow-up blood culture VS No routine follow-up blood culture |
Primary outcome
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
The primary outcome for each domain will use a Desirability of Outcome Ranking (DOOR) ordinal scale in which patients are categorized into the following mutually exclusive categories, ranked from best to worst status: 1. Alive with no reinfection or readmission. 2. Alive with reinfection OR readmission. 3. Alive with reinfection AND readmission. 4. Dead For the 3 antibiotic-related domains (the de-escalation versus no de-escalation domain, the beta-lactam versus non-beta-lactam domain, and the low risk AmpC domain) there will be an additional tie-breaker within ordinal levels 1, 2 and 3 based on whether there was new detection of antimicrobial resistance (AMR).
8 secondary outcomes
90-day mortality
Time frame: 90 days
90-day re-infection
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
Additional Secondary Outcomes for Individual Domains
Time frame: 90 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Nick Daneman, MD principal investigator
Sunnybrook Health Sciences Centre
Rob Fowler, MD principal investigator
Sunnybrook Health Sciences Centre
39 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing De-escalation VS No De-escalation, Oral beta-lactams VS non beta-lactams and Central vascular catheter retention VS Central vascular catheter replacement in people with Gram-negative Bacteremia, run by Sunnybrook Health Sciences Centre at 39 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 46 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 4 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 39 sites in Canada, Australia, Colombia, Israel, New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Nick Daneman, MD (4164806100 ext. 3862, nick.daneman@sunnybrook.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Sep 2026.