BacteremiaBALANCENCT03005145
Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness
A study testing 7 days of adequate antibiotic treatment and 14 days of adequate antibiotic treatment. in people with Bacteremia and Intensive Care, run by Sunnybrook Health Sciences Centre at 68 sites in 7 countries.
Trial summary
The World Health Organization, U.S. Centers for Disease Control and Prevention, Association of Medical Microbiology and Infectious Diseases (AMMI) Canada, and Health Canada have all declared antimicrobial resistance a global threat to health, based on rapidly increasing resistance rates and declining new drug… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bacteremia, Intensive Care, Critically Ill
- What is being tested?
- 7 days of adequate antibiotic treatment and 14 days of adequate antibiotic treatment.
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3,622 participants
- Where
- 68 sitesin 7 countries
- Study dates
- 24 Feb 2017to 3 Aug 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient is in ICU or non-ICU ward at the time the blood culture is drawn or reported as positive.
- Patient has a positive blood culture with pathogenic bacteria.
Who cannot join
- Patient already enrolled in the trial
- Patient has severe immune system compromise, as defined by: absolute neutrophil count <0.5x109/L; or is receiving immunosuppressive treatment for solid organ or bone marrow or stem cell transplant
- Patient has a prosthetic heart valve or synthetic endovascular graft (post major vessel repair with synthetic material) (note: coronary artery stents are not an exclusion)
- Patient has documented or suspected syndrome with well-defined requirement for prolonged treatment:
- infective endocarditis; ii) osteomyelitis/septic arthritis; iii) undrainable/undrained abscess; iv) unremovable/unremoved prosthetic-associated infection (e.g. infected pacemaker, prosthetic joint infection, ventriculoperitoneal shunt infection etc.) (note: central venous catheters, including tunneled central intravenous catheter, and urinary catheters are not excluded unless the treating clinical team does not have equipoise for enrollment and randomization to either group)
- Patient has a single positive blood culture with a common contaminant organism according to Clinical Laboratory \& Standards Institute (CLSI) Guidelines: coagulase negative staphylococci; or Bacillus spp.; or Corynebacterium spp.; or Propionobacterium spp.; or Aerococcus spp.; or Micrococcus spp.
Show all 9Show fewer
- Patient has a positive blood culture with Staphylococcus aureus or Staphylococcus lugdunensis
- Patient has a positive blood culture with Candida spp. or other fungal species.
- Blood culture grows rare bacterial pathogens requiring prolonged treatment (e.g. Mycobacteria spp., Nocardia spp., Actinomyces spp., Brucella spp., Burkholderia pseudomallei)
Trial locations and contacts
68 sites in 7 countries.
68 sites in 7 countries
Canada37 sites
William Osler Health System
Brampton, Ontario
Foothills Hospital
Calgary, Alberta
Peter Lougheed Centre
Calgary, Alberta
University of Alberta Hospital
Edmonton, Alberta
Health Sciences North
Greater Sudbury, Ontario
Queen Elizabeth II Hospital
Halifax, Nova Scotia
Brantford General Hospital
Hamilton, Ontario
Hamilton General Hospital
Hamilton, Ontario
St. Joseph's Healthcare
Hamilton, Ontario
Kingston General Hospital
Kingston, Ontario
London Health Sciences Centre
London, Ontario
Trillium Health Partners
Mississauga, Ontario
Centre hospitalier de l'Université de Montréal (CHUM)
Montreal, Quebec
Hospital Maisonneuve-Rosemont
Montreal, Quebec
Hospitalier Régional de Trois-Rivières
Montreal, Quebec
Montreal General Hospital
Montreal, Quebec
The Ottawa Hospital
Ottawa, Ontario
Centre hospitalier affilié universitaire de Québec
Québec, Quebec
Institut universitaire de cardiologie et de pneumologie de Québec
Québec, Quebec
Royal Victoria Hospital
Québec, Quebec
Université de Sherbrooke
Sherbrooke, Quebec
Niagara Health System
St. Catharines, Ontario
Eastern Regional Health Authority
St. John's, Newfoundland and Labrador
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N3M5
Michael Garron Hospital
Toronto, Ontario
Mount Sinai Hospital
Toronto, Ontario
North York General Hospital
Toronto, Ontario
St. Joseph's Health Centre
Toronto, Ontario
St. Michael's Hospital
Toronto, Ontario
Toronto General Hospital
Toronto, Ontario
Toronto Western Hospital
Toronto, Ontario
Lions Gate Hospital
Vancouver, British Columbia
Royal Columbian Hospital
Vancouver, British Columbia
St. Paul's Hospital
Vancouver, British Columbia
Vancouver General Hospital
Vancouver, British Columbia
Vancouver Island Health
Victoria, British Columbia
University of Manitoba
Winnipeg, Manitoba
Australia17 sites
Ballarat Hospital
Ballarat, Victoria
Bankstown Hospital
Bankstown, New South Wales
Bendigo Hospital
Bendigo, Victoria
Casey Hospital
Berwick, Victoria
Sunshine Coast University Hospital
Birtinya, Queensland
Monash Medical Centre
Clayton, Victoria
Dandenong Hospital- Monash Health
Dandenong, Victoria
St Vincent's Hospital
Darlinghurst, New South Wales
Frankston Hospital
Frankston, Victoria
St. George Hospital
Kogarah, New South Wales
Peninsula Private Hospital
Langwarrin, Victoria
Cabrini Health
Malvern, Victoria
Fiona Stanley Hospital
Murdoch, Western Australia
John Hunter Hospital
New Lambton Heights, New South Wales
St John of God Hospital
Subiaco, Western Australia
Westmead Hospital
Westmead, New South Wales
Wollongong Hospital ICU
Wollongong, New South Wales
New Zealand7 sites
Auckland City Hospital
Auckland
Middlemore Hospital
Auckland
Christchurch Hospital
Christchurch
Waikato Hospital
Hamilton
Taranaki Hospital
New Plymouth
Rotorua Hospital
Rotorua
Wellington Hospital
Wellington
United States2 sites
Cleveland Clinic
Cleveland, Ohio, 44195
NYU School of Medicine
New York, New York, 10016
Israel2 sites
Rabin Medical Center
Petah Tikva, Tel Aviv
Sheba Medical Center
Tel HaShomer, Tel Aviv
Saudi Arabia2 sites
King Faisal Specialist Hospital & Research Centre
Jeddah
King Abdulaziz Medical City
Riyadh
About this study
Official title: Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness: Randomized Controlled Trial
The World Health Organization, U.S. Centers for Disease Control and Prevention, Association of Medical Microbiology and Infectious Diseases (AMMI) Canada, and Health Canada have all declared antimicrobial resistance a global threat to health, based on rapidly increasing resistance rates and declining new drug development. Up to 30-50% of antibiotic use is inappropriate, and excessive durations of treatment are the greatest contributor to inappropriate use. Shorter duration treatment (≤7 days) has been shown in meta-analyses to be as effective as longer antibiotic treatment for a range of mild to moderate infections. A landmark trial in critically ill patients with ventilator-associated pneumonia showed that mortality and relapse rates were non-inferior in patients who received 8 vs 15 days of treatment. Similar adequately powered randomized trial evidence is lacking for the treatment of patients with bloodstream infections caused by a wide spectrum of organisms.
Read the detailed description
Bloodstream infections are a common and serious problem, increasing length of hospital stay by 2-3 weeks, adding $25,000-40,000 in excess hospital costs, and tripling the risk of death. At the same time, antibiotic overuse is also a common and serious problem, in that 30-50% of antibiotic use is unnecessary or inappropriate, and results in avoidable drug side effects such as kidney failure, Clostridioides difficile infection, increased costs, and spiralling antibiotic resistance rates. The greatest contributor to antibiotic overuse is excessive durations of treatment.
Extensive research has demonstrated that shorter duration antibiotic treatment (less or equal to 7 days) is as effective as longer duration treatment for a variety of infectious diseases, but this question has not been directly studied in the setting of bloodstream infection. BALANCE team's systematic review of the medical literature, national survey of Canadian infectious diseases and critical care physicians, multicentre retrospective study and BALANCE pilot RCT, all support the need for a randomized controlled trial comparing shorter (7 days) versus longer (14 days) antibiotic therapy for bloodstream infections. Prior to performing the main trial, Investigators completed a pilot trial in ICU patients to establish the feasibility of the research design, and to optimize the definitive trial. Investigators also completed a pilot trial of non-ICUs patients to test the feasibility, compare the patient population in two settings and to assess the reasonableness of expanding the main BALANCE Trial to non-ICU wards. The overall recruitment rate of the non-ICU ward pilot RCT exceeded the recruitment rate in the BALANCE ICU pilot RCT with a protocol adherence of 90%. The results of this pilot were used to estimate the necessary sample size recalculation, after merging the BALANCE ward trial with the BALANCE main trial, with the principle of maintaining an equal to smaller non-inferiority margin by the trial's completion. With the completion of this pilot RCT, the eligibility criteria for the BALANCE trial are also modified to broaden the inclusion of all bacteremic patients admitted to hospital. By defining the duration of treatment for bloodstream infections, BALANCE research program will help maximize the clinical cure of individual patients, while minimizing their risk of drug side effects, C. difficile, and antibiotic resistance. Since this intervention would require no new technology, and would reduce (rather than increase) health care costs, it would offer immediate benefits to patients and the healthcare system.
The BALANCE RCT will randomize hospitalized patients with bloodstream infection to 7 versus 14 days of adequate antibiotic treatment; the antibiotic drugs, doses, routes and interval will be left to the discretion of the treating team. Although placebo controls are not feasible, prolonged allocation concealment to day 7 will be used to mitigate selection bias. The primary analysis will assess whether 7 days is associated with non-inferior 90 day survival as compared to 14 days of treatment. Participants from the vanguard BALANCE pilot RCTs will be included in the BALANCE main RCT, and participating Canadian sites will continue to enrol patients. BALANCE international collaborators include New Zealand, Australia, Saudi Arabia, the United States, Israel and Switzerland.
- Conditions
- Bacteremia, Intensive Care, Critically Ill, Sepsis, Mortality, Antimicrobial
- Being tested
- 7 days of adequate antibiotic treatment, 14 days of adequate antibiotic treatment.
- Medical subject headings
- Bacteremia, Critical Illness, Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
7 days of adequate antibiotic treatmentOther
The choice of treatment including type, dose, route and interval of antibiotic will be left at the discretion of treating team as long as it is appropriate for the bacteremia
14 days of adequate antibiotic treatment.Other
The choice of treatment including type, dose, route and interval of antibiotic will be left at the discretion of treating team as long as it is appropriate for the bacteremia
| Study group | Role | What they receive |
|---|---|---|
| Short duration (7 days) | Active comparator | Patients in 7 day arm will receive adequate antibiotics until the end of day 7 only Receives: Other: 7 days of adequate antibiotic treatment |
| Long duration (14 days) | Active comparator | Patients in 14 day arm will receive adequate antibiotics until the end of day 14 only Receives: Other: 14 days of adequate antibiotic treatment. |
What is being measured
The primary outcome is the main question the study is designed to answer.
90 day survival
Survival at 90-days recorded as alive or dead at day 90 following index positive blood culture
Measured: 90 days from index blood culture
Secondary outcomes (10)
Hospital mortality
Recorded as alive or dead at hospital discharge following index positive blood culture
Measured: Expected average of 4 weeks assessed upto one year
ICU mortality
Recorded as alive or dead at ICU discharge following index positive blood culture
Measured: Expected average of 2 weeks assessed upto one year
Relapse rates of bacteremia with the same organism
Defined as the recurrence of bacteremia due to original infecting organism (same Genus and species) after documentation of negative blood cultures or clinical improvement and within 30 days after completing course of adequate antimicrobial therapy.
Measured: Upto 30 days after adequate antibiotic treatment
Antibiotic allergy and adverse events
Effect of medication on body that produces the allergic reaction to a medication like:
- Hives
- Itching of the skin or eyes
- Skin rash
- Swelling of the lips, tongue, or face
- Wheezing
- Organ toxicity
Measured: Upto 30 days from start of antibiotic treatment
Rates of C. difficile infection in hospital
Defined as a positive PCR or ELISA test for Clostridium difficile toxin in the context of diarrhea within hospital of bacteremia diagnosis.
Measured: Upto 30 days after index blood culture collection date
Rates of secondary nosocomial infection/colonization with antimicrobial resistant organisms in hospital
Colonized or infected with at least one highly-resistant microorganism during their hospital stay
Measured: Upto 30 days after index blood culture collection date
ICU length of stay
Defined as the duration between index blood culture and discharge from the ICU for a consecutive 48-hour period
Measured: Expected for an average of 30 days assessed up to 1 year
Hospital length of stay
Defined as the duration between index blood culture and discharge date from hospital
Measured: Expected for an average of 30 days assessed up to 1 year
Mechanical ventilation duration
Defined as the number of consecutive days receiving invasive (via an endotracheal tube or tracheostomy), or non-invasive (via a facemask, nasal mask, or helmet) ventilation
Measured: Expected for an average of 30 days
Antibiotic free days
Defined as the number of days during the 28 days after the start of adequate antibiotics in which patients did not receive any antibiotics.
Measured: Upto 30 days after adequate antibiotic treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Dec 2016 (estimated)
- Study start24 Feb 2017
- Primary completion5 May 2023
- Study completion3 Aug 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for 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
- 3,622 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sunnybrook Health Sciences Centre
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nick Daneman, MD, Principal investigator, Sunnybrook Health Sciences Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03005145
- Sponsor's protocol ID
- 0796
- Acronym
- BALANCE
- Status last verified
- Nov 2023
- First submitted
- 20 Dec 2016
- Last updated
- 29 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ong SWX, Pinto R, Rishu A, Tong SYC, Commons RJ, Conly JM, Evans GA, Fralick M, Kandel C, Lagace-Wiens PRS, Lee TC, Lother SA, MacFadden DR, Marshall JC, Martel-Laferriere V, Mayette M, McDonald EG, Neary JD, Prazak J, Raby E, Regli A, Rogers BA, Smith S, Taggart LR, Wang HT, Wuerz T, Yahav D, Young PJ, Fowler RA, Daneman N; BALANCE trial consortium. Identifying heterogeneity of treatment effect for antibiotic duration in bloodstream infection: an exploratory post-hoc analysis of the BALANCE randomised clinical trial. EClinicalMedicine. 2025 Apr 10;83:103195. doi: 10.1016/j.eclinm.2025.103195. eCollection 2025 May.
PubMed 40256773BALANCE Investigators, for the Canadian Critical Care Trials Group, the Association of Medical Microbiology and Infectious Disease Canada Clinical Research Network, the Australian and New Zealand Intensive Care Society Clinical Trials Group, and the Australasian Society for Infectious Diseases Clinical Research Network; Daneman N, Rishu A, Pinto R, Rogers BA, Shehabi Y, Parke R, Cook D, Arabi Y, Muscedere J, Reynolds S, Hall R, Dwivedi DB, McArthur C, McGuinness S, Yahav D, Coburn B, Geagea A, Das P, Shin P, Detsky M, Morris A, Fralick M, Powis JE, Kandel C, Sligl W, Bagshaw SM, Singhal N, Belley-Cote E, Whitlock R, Khwaja K, Morpeth S, Kazemi A, Williams A, MacFadden DR, McIntyre L, Tsang J, Lamontagne F, Carignan A, Marshall J, Friedrich JO, Cirone R, Downing M, Graham C, Davis J, Duan E, Neary J, Evans G, Alraddadi B, Al Johani S, Martin C, Elsayed S, Ball I, Lauzier F, Turgeon A, Stelfox HT, Conly J, McDonald EG, Lee TC, Sullivan R, Grant J, Kagan I, Young P, Lawrence C, O'Callaghan K, Eustace M, Choong K, Aslanian P, Buehner U, Havey T, Binnie A, Prazak J, Reeve B, Litton E, Lother S, Kumar A, Zarychanski R, Hoffman T, Paterson D, Daley P, Commons RJ, Charbonney E, Naud JF, Roberts S, Tiruvoipati R, Gupta S, Wood G, Shum O, Miyakis S, Dodek P, Kwok C, Fowler RA; The BALANCE Investigators, for the Canadian Critical Care Trials Group, the Association of Medical Microbiology and Infectious Disease Canada Clinical Research Network, the Australian and New Zealand Intensive Care Society Clinical Trials Group, and the Australasian Society for Infectious Diseases Clinical Research Network. Antibiotic Treatment for 7 versus 14 Days in Patients with Bloodstream Infections. N Engl J Med. 2025 Mar 13;392(11):1065-1078. doi: 10.1056/NEJMoa2404991. Epub 2024 Nov 20.
PubMed 39565030Rogers BA, Fowler R, Harris PNA, Davis JS, Pinto RL, Bhatia Dwivedi D, Rishu A, Shehabi Y, Daneman N. Non-inferiority trial of a shorter (7 days) compared with a longer (14 days) duration of antimicrobial therapy for the treatment of bacteraemic urinary sepsis, measured by microbiological success after the completion of therapy: a substudy protocol for the Bacteraemia Antibiotic Length Actually Needed for Clinical Effectiveness (BALANCE) multicentre randomised controlled trial. BMJ Open. 2023 Jun 26;13(6):e069708. doi: 10.1136/bmjopen-2022-069708.
PubMed 37369422Daneman N, Rishu AH, Pinto RL, Arabi YM, Cook DJ, Hall R, McGuinness S, Muscedere J, Parke R, Reynolds S, Rogers B, Shehabi Y, Fowler RA; Canadian Critical Care Trials Group. Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness (BALANCE) randomised clinical trial: study protocol. BMJ Open. 2020 May 11;10(5):e038300. doi: 10.1136/bmjopen-2020-038300.
PubMed 32398341
Study at a glance
From the registry record, last updated by the sponsor on 29 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness: Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT03005145
- Acronym / sponsor ID
- BALANCE / 0796
- Conditions
- Bacteremia, Intensive Care, Critically Ill, Sepsis, Mortality, Antimicrobial
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3,622 participants (actual)
- Lead sponsor
- Sunnybrook Health Sciences CentreUniversity, hospital or other
- Study start
- 24 Feb 2017 (actual)
- Primary completion
- 5 May 2023 (actual)
- Study completion
- 3 Aug 2023 (actual)
- First posted
- 29 Dec 2016 (estimated)
- 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.
The World Health Organization, U.S. Centers for Disease Control and Prevention, Association of Medical Microbiology and Infectious Diseases (AMMI) Canada, and Health Canada have all declared antimicrobial resistance a global threat to health, based on rapidly increasing resistance rates and declining new drug development. Up to 30-50% of antibiotic use is inappropriate, and excessive durations of treatment are the greatest contributor to inappropriate use. Shorter duration treatment (≤7 days) has been shown in meta-analyses to be as effective as longer antibiotic treatment for a range of mild to moderate infections. A landmark trial in critically ill patients with ventilator-associated pneumonia showed that mortality and relapse rates were non-inferior in patients who received 8 vs 15 days of treatment. Similar adequately powered randomized trial evidence is lacking for the treatment of patients with bloodstream infections caused by a wide spectrum of organisms.
Detailed description
Bloodstream infections are a common and serious problem, increasing length of hospital stay by 2-3 weeks, adding $25,000-40,000 in excess hospital costs, and tripling the risk of death. At the same time, antibiotic overuse is also a common and serious problem, in that 30-50% of antibiotic use is unnecessary or inappropriate, and results in avoidable drug side effects such as kidney failure, Clostridioides difficile infection, increased costs, and spiralling antibiotic resistance rates. The greatest contributor to antibiotic overuse is excessive durations of treatment.
Extensive research has demonstrated that shorter duration antibiotic treatment (less or equal to 7 days) is as effective as longer duration treatment for a variety of infectious diseases, but this question has not been directly studied in the setting of bloodstream infection. BALANCE team's systematic review of the medical literature, national survey of Canadian infectious diseases and critical care physicians, multicentre retrospective study and BALANCE pilot RCT, all support the need for a randomized controlled trial comparing shorter (7 days) versus longer (14 days) antibiotic therapy for bloodstream infections. Prior to performing the main trial, Investigators completed a pilot trial in ICU patients to establish the feasibility of the research design, and to optimize the definitive trial. Investigators also completed a pilot trial of non-ICUs patients to test the feasibility, compare the patient population in two settings and to assess the reasonableness of expanding the main BALANCE Trial to non-ICU wards. The overall recruitment rate of the non-ICU ward pilot RCT exceeded the recruitment rate in the BALANCE ICU pilot RCT with a protocol adherence of 90%. The results of this pilot were used to estimate the necessary sample size recalculation, after merging the BALANCE ward trial with the BALANCE main trial, with the principle of maintaining an equal to smaller non-inferiority margin by the trial's completion. With the completion of this pilot RCT, the eligibility criteria for the BALANCE trial are also modified to broaden the inclusion of all bacteremic patients admitted to hospital. By defining the duration of treatment for bloodstream infections, BALANCE research program will help maximize the clinical cure of individual patients, while minimizing their risk of drug side effects, C. difficile, and antibiotic resistance. Since this intervention would require no new technology, and would reduce (rather than increase) health care costs, it would offer immediate benefits to patients and the healthcare system.
The BALANCE RCT will randomize hospitalized patients with bloodstream infection to 7 versus 14 days of adequate antibiotic treatment; the antibiotic drugs, doses, routes and interval will be left to the discretion of the treating team. Although placebo controls are not feasible, prolonged allocation concealment to day 7 will be used to mitigate selection bias. The primary analysis will assess whether 7 days is associated with non-inferior 90 day survival as compared to 14 days of treatment. Participants from the vanguard BALANCE pilot RCTs will be included in the BALANCE main RCT, and participating Canadian sites will continue to enrol patients. BALANCE international collaborators include New Zealand, Australia, Saudi Arabia, the United States, Israel and Switzerland.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Short duration (7 days) | Active comparator | Other: 7 days of adequate antibiotic treatmentPatients in 7 day arm will receive adequate antibiotics until the end of day 7 only |
| Long duration (14 days) | Active comparator | Other: 14 days of adequate antibiotic treatment.Patients in 14 day arm will receive adequate antibiotics until the end of day 14 only |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patient is in ICU or non-ICU ward at the time the blood culture is drawn or reported as positive.
- Patient has a positive blood culture with pathogenic bacteria.
Key exclusion criteria (9 listed)
- Patient already enrolled in the trial
- Patient has severe immune system compromise, as defined by: absolute neutrophil count <0.5x109/L; or is receiving immunosuppressive treatment for solid organ or bone marrow or stem cell transplant
- Patient has a prosthetic heart valve or synthetic endovascular graft (post major vessel repair with synthetic material) (note: coronary artery stents are not an exclusion)
- Patient has documented or suspected syndrome with well-defined requirement for prolonged treatment:
- Patient has a single positive blood culture with a common contaminant organism according to Clinical Laboratory \& Standards Institute (CLSI) Guidelines: coagulase negative staphylococci; or Bacillus spp.; or Corynebacterium spp.; or Propionobacterium spp.; or Aerococcus spp.; or Micrococcus spp.
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 |
|---|---|---|
| 7 days of adequate antibiotic treatmentThe choice of treatment including type, dose, route and interval of antibiotic will be left at the discretion of treating team as long as it is appropriate for the bacteremia | Other | Short duration (7 days) |
| 14 days of adequate antibiotic treatment.The choice of treatment including type, dose, route and interval of antibiotic will be left at the discretion of treating team as long as it is appropriate for the bacteremia | Other | Long duration (14 days) |
Primary outcome
90 day survival
Time frame: 90 days from index blood culture
Survival at 90-days recorded as alive or dead at day 90 following index positive blood culture
10 secondary outcomes
Hospital mortality
Time frame: Expected average of 4 weeks assessed upto one year
ICU mortality
Time frame: Expected average of 2 weeks assessed upto one year
Relapse rates of bacteremia with the same organism
Time frame: Upto 30 days after adequate antibiotic treatment
Antibiotic allergy and adverse events
Time frame: Upto 30 days from start of antibiotic treatment
Rates of C. difficile infection in hospital
Time frame: Upto 30 days after index blood culture collection date
Rates of secondary nosocomial infection/colonization with antimicrobial resistant organisms in hospital
Time frame: Upto 30 days after index blood culture collection date
ICU length of stay
Time frame: Expected for an average of 30 days assessed up to 1 year
Hospital length of stay
Time frame: Expected for an average of 30 days assessed up to 1 year
Mechanical ventilation duration
Time frame: Expected for an average of 30 days
Antibiotic free days
Time frame: Upto 30 days after adequate antibiotic treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Feb 2024.
- Derived from this study: PubMed 40256773Ong SWX, Pinto R, Rishu A, Tong SYC, Commons RJ, Conly JM, Evans GA, Fralick M, Kandel C, Lagace-Wiens PRS, Lee TC, Lother SA, MacFadden DR, Marshall JC, Martel-Laferriere V, Mayette M, McDonald EG, Neary JD, Prazak J, Raby E, Regli A, Rogers BA, Smith S, Taggart LR, Wang HT, Wuerz T, Yahav D, Young PJ, Fowler RA, Daneman N; BALANCE trial consortium. Identifying heterogeneity of treatment effect for antibiotic duration in bloodstream infection: an exploratory post-hoc analysis of the BALANCE randomised clinical trial. EClinicalMedicine. 2025 Apr 10;83:103195. doi: 10.1016/j.eclinm.2025.103195. eCollection 2025 May.
- Derived from this study: PubMed 39565030BALANCE Investigators, for the Canadian Critical Care Trials Group, the Association of Medical Microbiology and Infectious Disease Canada Clinical Research Network, the Australian and New Zealand Intensive Care Society Clinical Trials Group, and the Australasian Society for Infectious Diseases Clinical Research Network; Daneman N, Rishu A, Pinto R, Rogers BA, Shehabi Y, Parke R, Cook D, Arabi Y, Muscedere J, Reynolds S, Hall R, Dwivedi DB, McArthur C, McGuinness S, Yahav D, Coburn B, Geagea A, Das P, Shin P, Detsky M, Morris A, Fralick M, Powis JE, Kandel C, Sligl W, Bagshaw SM, Singhal N, Belley-Cote E, Whitlock R, Khwaja K, Morpeth S, Kazemi A, Williams A, MacFadden DR, McIntyre L, Tsang J, Lamontagne F, Carignan A, Marshall J, Friedrich JO, Cirone R, Downing M, Graham C, Davis J, Duan E, Neary J, Evans G, Alraddadi B, Al Johani S, Martin C, Elsayed S, Ball I, Lauzier F, Turgeon A, Stelfox HT, Conly J, McDonald EG, Lee TC, Sullivan R, Grant J, Kagan I, Young P, Lawrence C, O'Callaghan K, Eustace M, Choong K, Aslanian P, Buehner U, Havey T, Binnie A, Prazak J, Reeve B, Litton E, Lother S, Kumar A, Zarychanski R, Hoffman T, Paterson D, Daley P, Commons RJ, Charbonney E, Naud JF, Roberts S, Tiruvoipati R, Gupta S, Wood G, Shum O, Miyakis S, Dodek P, Kwok C, Fowler RA; The BALANCE Investigators, for the Canadian Critical Care Trials Group, the Association of Medical Microbiology and Infectious Disease Canada Clinical Research Network, the Australian and New Zealand Intensive Care Society Clinical Trials Group, and the Australasian Society for Infectious Diseases Clinical Research Network. Antibiotic Treatment for 7 versus 14 Days in Patients with Bloodstream Infections. N Engl J Med. 2025 Mar 13;392(11):1065-1078. doi: 10.1056/NEJMoa2404991. Epub 2024 Nov 20.
- Derived from this study: PubMed 37369422Rogers BA, Fowler R, Harris PNA, Davis JS, Pinto RL, Bhatia Dwivedi D, Rishu A, Shehabi Y, Daneman N. Non-inferiority trial of a shorter (7 days) compared with a longer (14 days) duration of antimicrobial therapy for the treatment of bacteraemic urinary sepsis, measured by microbiological success after the completion of therapy: a substudy protocol for the Bacteraemia Antibiotic Length Actually Needed for Clinical Effectiveness (BALANCE) multicentre randomised controlled trial. BMJ Open. 2023 Jun 26;13(6):e069708. doi: 10.1136/bmjopen-2022-069708.
- Derived from this study: PubMed 32398341Daneman N, Rishu AH, Pinto RL, Arabi YM, Cook DJ, Hall R, McGuinness S, Muscedere J, Parke R, Reynolds S, Rogers B, Shehabi Y, Fowler RA; Canadian Critical Care Trials Group. Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness (BALANCE) randomised clinical trial: study protocol. BMJ Open. 2020 May 11;10(5):e038300. doi: 10.1136/bmjopen-2020-038300.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Nick Daneman, MD principal investigator
Sunnybrook Health Sciences Centre
68 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 7 days of adequate antibiotic treatment and 14 days of adequate antibiotic treatment. in people with Bacteremia and Intensive Care, run by Sunnybrook Health Sciences Centre at 68 sites in 7 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 2 inclusion and 9 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: finished, as of the sponsor's last update on 29 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 68 sites in Canada, Australia, New Zealand, United States, Israel and 2 more countries. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
90 day survival (time frame: 90 days from index blood culture). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03005145, which also lists 4 linked publications.
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 29 Feb 2024.