ALternatives To prophylactic Antibiotics for the treatment of Recurrent urinary tract infection in women (ALTAR): study protocol for a multicentre, pragmatic, patient-randomised, non-inferiority trial

At least half of all adult women will experience infective cystitis (urinary tract infection: UTI) at least once in their life and many suffer from repeated episodes. Recurrent urinary tract infection (rUTI) in adult women is usually treated with long-term, low-dose antibiotics and current national and international guidelines recommend this as the 'gold standard' preventative treatment. Although they are reasonably effective, long-term antibiotics can result in bacteria becoming resistant not only to the prescribed antibiotic but to other antimicrobial agents. The problem of antimicrobial resistance is recognised as a global threat and the recent drive for antibiotic stewardship has emphasised the need for careful consideration prior to prescribing antibiotics. This has led clinicians and patients alike to explore potential non-antibiotic options for recurrent UTI prevention.

This is a multicentre, pragmatic, patient-randomised, non-inferiority trial comparing a non-antibiotic preventative treatment for rUTI in women, methenamine hippurate, against the current standard of daily low-dose antibiotics. Women who require preventative treatment for rUTI are the target population. This group is comprised of those with a diagnosis of rUTI, defined as three episodes in 1 year or two episodes in 6 months, and those with a single severe infection requiring hospitalisation. Participants will be recruited from secondary care urology / urogynaecology departments in the UK following referral with rUTI. Participants will be followed up during a 12-month period of treatment and in the subsequent 6 months following completion of the prophylactic medication. Outcomes will be assessed from patient recorded symptoms, quality of life questionnaires and microbiological examination of urine and perineal swabs. The primary outcome is the incidence of symptomatic antibiotic-treated UTI self-reported by participants during the 12-month period of preventative treatment. Health economic outcomes will also be assessed to define the cost-effectiveness of both treatments. A qualitative study will be conducted in the first 8 months of the trial to explore with participants/non-participants' and recruiting clinicians' views on trial processes and identify potential barriers to recruitment, reasons for participating and non-participation and for dropping out of the study.

The study was commissioned and funded by the National Institute for Health Research (NIHR) and approved under the Medicines and Healthcare products Regulatory Agency (MHRA) notification scheme as a 'Type A' study.

International Standard Randomised Controlled Trial Number (ISRCTN), registry number: ISRCTN70219762 . Registered on 31 May 2016.

Trials. 2018 Nov 09*** epublish ***

Rebecca Forbes, Ased Ali, Alaa Abouhajar, Catherine Brennand, Heather Brown, Sonya Carnell, Thomas Chadwick, Ian Eardley, Jan Lecouturier, Helen Mossop, Ian Pearce, Robert Pickard, Nikesh Thiruchelvam, Katherine Walton, Jennifer Wilkinson, Chris Harding

Newcastle Clinical Trials Unit, Newcastle University, 1-4 Claremont Terrace, Newcastle upon Tyne, NE2 4AE, UK., Pinderfields Hospital, Wakefield, WF1 4EE, UK., Institute of Health and Society, Newcastle University, Newcastle upon Tyne, NE2 4AX, UK., St James's University Hospital, Leeds, LS9 7TF, UK., Manchester Royal Infirmary, Manchester, M13 9WL, UK., Institute of Cellular Medicine, William Leech Building, The Medical School, Newcastle upon Tyne, NE2 4HH,, UK., Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK., Department of Microbiology, Freeman Hospital, Newcastle upon Tyne, NE7 7DN, UK., Department of Urology, Freeman Hospital, Freeman Road, Newcastle upon Tyne, NE7 7DN, UK. .