Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness

NCT03005145 | Completed DMC

• 1 other identifier: 0796
• Study Type: interventional
• Target: 3,622
• Locations: 7 countries
• Sites: 68

Brief 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 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.

Conditions

Bacteremia; Intensive Care; Critically Ill; Sepsis; Mortality; Antimicrobial

Outcome Measures

Primary Outcomes (1)

• 90 day survival

  Survival at 90-days recorded as alive or dead at day 90 following index positive blood culture

  90 days from index blood culture

Secondary Outcomes (10)

• Hospital mortality

  Expected average of 4 weeks assessed upto one year

• ICU mortality

  Expected average of 2 weeks assessed upto one year

• Relapse rates of bacteremia with the same organism

  Upto 30 days after adequate antibiotic treatment

• Antibiotic allergy and adverse events

  Upto 30 days from start of antibiotic treatment

• Rates of C. difficile infection in hospital

  Upto 30 days after index blood culture collection date

Study Arms (2)

Short duration (7 days)

ACTIVE COMPARATOR

Patients in 7 day arm will receive adequate antibiotics until the end of day 7 only

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

Other: 14 days of adequate antibiotic treatment.

Interventions

7 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

Short duration (7 days)

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

Long duration (14 days)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 documented or suspected syndrome with well-defined requirement for prolonged treatment:
• i) 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.
• 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)

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead

Study Sites (68)

NYU School of Medicine

New York, New York, 10016, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Bankstown Hospital

Bankstown, New South Wales, Australia

Location

St Vincent's Hospital

Darlinghurst, New South Wales, Australia

Location

St. George Hospital

Kogarah, New South Wales, Australia

Location

John Hunter Hospital

New Lambton Heights, New South Wales, Australia

Location

Westmead Hospital

Westmead, New South Wales, Australia

Location

Wollongong Hospital ICU

Wollongong, New South Wales, Australia

Location

Sunshine Coast University Hospital

Birtinya, Queensland, Australia

Location

Ballarat Hospital

Ballarat, Victoria, Australia

Location

Bendigo Hospital

Bendigo, Victoria, Australia

Location

Casey Hospital

Berwick, Victoria, Australia

Location

Monash Medical Centre

Clayton, Victoria, Australia

Location

Dandenong Hospital- Monash Health

Dandenong, Victoria, Australia

Location

Frankston Hospital

Frankston, Victoria, Australia

Location

Peninsula Private Hospital

Langwarrin, Victoria, Australia

Location

Cabrini Health

Malvern, Victoria, Australia

Location

Fiona Stanley Hospital

Murdoch, Western Australia, Australia

Location

St John of God Hospital

Subiaco, Western Australia, Australia

Location

Foothills Hospital

Calgary, Alberta, Canada

Location

Peter Lougheed Centre

Calgary, Alberta, Canada

Location

University of Alberta Hospital

Edmonton, Alberta, Canada

Location

Lions Gate Hospital

Vancouver, British Columbia, Canada

Location

Royal Columbian Hospital

Vancouver, British Columbia, Canada

Location

St. Paul's Hospital

Vancouver, British Columbia, Canada

Location

Vancouver General Hospital

Vancouver, British Columbia, Canada

Location

Vancouver Island Health

Victoria, British Columbia, Canada

Location

University of Manitoba

Winnipeg, Manitoba, Canada

Location

Eastern Regional Health Authority

St. John's, Newfoundland and Labrador, Canada

Location

Queen Elizabeth II Hospital

Halifax, Nova Scotia, Canada

Location

William Osler Health System

Brampton, Ontario, Canada

Location

Health Sciences North

Greater Sudbury, Ontario, Canada

Location

Brantford General Hospital

Hamilton, Ontario, Canada

Location

Hamilton General Hospital

Hamilton, Ontario, Canada

Location

St. Joseph's Healthcare

Hamilton, Ontario, Canada

Location

Kingston General Hospital

Kingston, Ontario, Canada

Location

London Health Sciences Centre

London, Ontario, Canada

Location

Trillium Health Partners

Mississauga, Ontario, Canada

Location

The Ottawa Hospital

Ottawa, Ontario, Canada

Location

Niagara Health System

St. Catharines, Ontario, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N3M5, Canada

Location

Michael Garron Hospital

Toronto, Ontario, Canada

Location

Mount Sinai Hospital

Toronto, Ontario, Canada

Location

North York General Hospital

Toronto, Ontario, Canada

Location

St. Joseph's Health Centre

Toronto, Ontario, Canada

Location

St. Michael's Hospital

Toronto, Ontario, Canada

Location

Toronto General Hospital

Toronto, Ontario, Canada

Location

Toronto Western Hospital

Toronto, Ontario, Canada

Location

Centre hospitalier de l'Université de Montréal (CHUM)

Montreal, Quebec, Canada

Location

Hospital Maisonneuve-Rosemont

Montreal, Quebec, Canada

Location

Hospitalier Régional de Trois-Rivières

Montreal, Quebec, Canada

Location

Montreal General Hospital

Montreal, Quebec, Canada

Location

Centre hospitalier affilié universitaire de Québec

Québec, Quebec, Canada

Location

Institut universitaire de cardiologie et de pneumologie de Québec

Québec, Quebec, Canada

Location

Royal Victoria Hospital

Québec, Quebec, Canada

Location

Université de Sherbrooke

Sherbrooke, Quebec, Canada

Location

Rabin Medical Center

Petah Tikva, Tel Aviv, Israel

Location

Sheba Medical Center

Tel Litwinsky, Tel Aviv, Israel

Location

Auckland City Hospital

Auckland, New Zealand

Location

Middlemore Hospital

Auckland, New Zealand

Location

Christchurch Hospital

Christchurch, New Zealand

Location

Waikato Hospital

Hamilton, New Zealand

Location

Taranaki Hospital

New Plymouth, New Zealand

Location

Rotorua Hospital

Rotorua, New Zealand

Location

Wellington Hospital

Wellington, New Zealand

Location

King Faisal Specialist Hospital & Research Centre

Jeddah, Saudi Arabia

Location

King Abdulaziz Medical City

Riyadh, Saudi Arabia

Location

University hospital Bern

Bern, Switzerland

Location

Related Publications (4)

• 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.

  PMID: 40256773 DERIVED

• 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; 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.

  PMID: 39565030 DERIVED

• Rogers 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.

  PMID: 37369422 DERIVED

• Daneman 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.

  PMID: 32398341 DERIVED

MeSH Terms

Conditions

Bacteremia; Critical Illness; Sepsis

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Study Officials

• Nick Daneman, MD

  Sunnybrook Health Sciences Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2016
• First Posted: December 29, 2016
• Study Start: February 24, 2017
• Primary Completion: May 5, 2023
• Study Completion: August 3, 2023
• Last Updated: February 29, 2024

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

AU (17); NZ (7); US (2); IL (2); SA (2); CA (37); CH (1)