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Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness (BALANCE) randomised clinical trial: study protocol
  1. Nick Daneman1,
  2. Asgar H Rishu2,
  3. Ruxandra L Pinto3,
  4. Yaseen M Arabi4,
  5. Deborah J Cook5,
  6. Richard Hall6,
  7. Shay McGuinness7,
  8. John Muscedere8,
  9. Rachael Parke9,
  10. Steven Reynolds10,
  11. Benjamin Rogers11,
  12. Yahya Shehabi12,
  13. Robert A Fowler13
  14. On behalf of the Canadian Critical Care Trials Group
  1. 1Division of Infectious Diseases & Clinical Epidemiology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
  2. 2Institute for Clinical Evaluative Sciences, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
  3. 3Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
  4. 4Intensive Care Department, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
  5. 5McMaster University, Hamilton, Ontario, Canada
  6. 6Departments of Critical Care Medicine and Anesthesiology, Pain Management and Perioperative Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
  7. 7Auckland City Hospital, Auckland, New Zealand
  8. 8Kingston General Hospital, Kingston, Ontario, Canada
  9. 9The University of Auckland, Auckland, New Zealand
  10. 10Royal Columbian Hospital, New Westminster, British Columbia, Canada
  11. 11Centre for Inflammatory Diseases, Monash University School of Clinical Sciences, Melborne, Victoria, Australia
  12. 12Critical Care and Perioperative Medicine, School of Clinical Sciences, Monash University and Monash Health, Melbourne, Victoria, Australia
  13. 13Departments of Medicine and Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
  1. Correspondence to Dr Nick Daneman; Nick.Daneman{at}sunnybrook.ca

Abstract

Introduction Bloodstream infections are a leading cause of mortality and morbidity; the duration of treatment for these infections is understudied.

Methods and analysis We will conduct an international, multicentre randomised clinical trial of shorter (7 days) versus longer (14 days) antibiotic treatment among hospitalised patients with bloodstream infections. The trial will include 3626 patients across 60 hospitals and 6 countries. We will include patients with blood cultures confirming a pathogenic bacterium after hospital admission. Exclusion criteria will include patient factors (severe immunosuppression), infection site factors (endocarditis, osteomyelitis, undrained abscesses, infected prosthetic material) and pathogen factors (Staphylococcus aureus, Staphylococcus lugdunensis, Candida and contaminant organisms). We will leave the selection of specific antibiotics, doses and route of delivery to the discretion of treating physicians; no placebo control will be used given the diversity of pathogens and sources of bacteraemia. The intervention will be assignment of treatment duration to be 7 versus 14 days. We will minimise selection bias via central randomisation with variable block sizes, with concealed allocation until day 7 of adequate antibiotic treatment. The primary outcome is 90-day survival; we will test whether 7 days is non-inferior to 14 days of treatment, with a non-inferiority margin of 4% absolute mortality. Secondary outcomes include hospital and intensive care unit (ICU) mortality, relapse rates of bacteraemia, hospital and ICU length of stay, mechanical ventilation and vasopressor duration, antibiotic-free days, Clostridium difficile infection, antibiotic allergy and adverse events and colonisation/infection with antibiotic-resistant organisms.

Ethics and dissemination The study has been approved by the ethics review board at each participating site. Sunnybrook Health Sciences Centre is the central ethics committee. We will disseminate study results via the Canadian Critical Care Trials Group and other collaborating networks to set the global paradigm for antibiotic treatment duration for non-staphylococcal Gram-positive, Gram-negative and anaerobic bacteraemia, among patients admitted to hospital.

Trial registration number The BALANCE (Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness) trial was registered at www.clinicaltrials.gov (registration number: NCT03005145).

  • adult intensive & critical care
  • infectious diseases
  • bacteriology
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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Footnotes

  • Contributors ND and RAF conceived the research question. ND and RAF designed the study, with crucial inputs from AHR, RP, YMA, DJC, RH, SPM, JM, RP, SR, BR and YS. ND and RAF drafted the manuscript with important revisions provided by AHR, RP, YMA, DJC, RH, SPM, JM, RP, SR, BR and YS.

  • Funding The BALANCE RCT is supported by a Project Grant from the Canadian Institutes of Health Research (CIHR), as well as grants from the New Zealand Health Research Council, and the Australian National Medical Health Research Council. BALANCE preparatory work and substudies have also received support from CIHR as well as Physicians Services Incorporated, the Canadian Frailty Network and The Ontario Ministry of Health and Long Term Care (MOHLTC) Alternate Funding Plan Innovation Fund Award.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were involved in the design, conduct, reporting or dissemination plans of this research. Refer to the Methods and analysis section for further details.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; peer reviewed for ethical and funding approval prior to submission.

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