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

Abstract

Introduction: The BALANCE study is a randomised clinical trial (3626 participants) designed to assess the non-inferiority of 7 days (short-course) antibiotic therapy compared with 14 days of therapy for bacteraemia using the pragmatic endpoint of 90-day survival. Based on pilot study data, approximately 30% of enrolees will have a urinary tract infection (UTI) as the source of bacteraemia.

Methods and analysis: We aim to assess the non-inferiority of short-course antibiotic therapy for patients with bacteraemia UTIs.Participating sites in four countries will be invited to join this substudy. All participants of this substudy will be enrolled in the main BALANCE study. The intervention will be assigned and treatment administered as specified in the main protocol.We will include participants in this substudy if the probable source of their infection is a UTI, as judged by the site principal investigator, and they have a urine microscopy and culture indicative of a UTI. Participants will be excluded if they have an ileal loop, vesicoureteric reflux or suspected or confirmed prostatitis.The primary outcome is the absence of a positive culture on a test-of-cure urine sample collected 6-12 days after cessation of antimicrobials, with a non-inferiority margin of 15%. Secondary outcomes include the clinical resolution of infection symptoms at test-of-cure.

Ethics and dissemination: The study has been approved in conjunction with the main BALANCE study through the relevant ethics review process at each participating site. We will disseminate the results through the Australasian Society for Infectious Diseases, Canadian Critical Care Trials Group, the Association for Medical Microbiology and Infectious Diseases Canada Clinical Research Network (AMMI Canada CRN) and other collaborators.

Universal trial number: U1111-1256-0874.

Main balance trial registration: NCT03005145.

Trial registration number: Australian Clinical Trial Register: ACTRN12620001108909.

Keywords: clinical trials; infectious diseases; intensive & critical care; urinary tract infections.