EVOLUTION Trial: EValuating a nOveL UTI dIagnOstic for aNtibiotic stewardship

Research question In adult women presenting to primary care with suspected urinary tract infection, does an assessment that includes testing with the Sysmex Astrego PA-100, compared to current usual care assessment alone reduce antibiotic prescriptions over 28 days (superiority) without negatively impacting recovery within 7 days (non-inferiority). Background Half of all women will experience a UTI in their lifetime. Current diagnostics are not fit for purpose in primary care, resulting in the majority of women receiving empirical antibiotics that account for 6 million prescriptions annually in the UK. A step change in our approach to antibiotic stewardship is urgently required if we are to preserve the usefulness of our antibiotics for ourselves and for future generations. Diagnostics that provide clinically actionable information at the point of care will be mission-critical. The revolutionary, first-in-class Sysmex Astrego PA-100 detects bacterial urinary tract infection within 15 minutes and determines whether the bacteria are sensitive to commonly prescribed antibiotics within 45 minutes, allowing clinicians and patients to use results to inform prescribing decisions within every-day general practice care pathways. We aim to: 1) Determine whether a clinical assessment process that includes the PA-100 compared to usual care assessment reduces antibiotic prescription without unduly prolonging symptoms in women presenting to primary care with suspected uncomplicated UTI 2) Understand the experiences of women and clinicians using the new diagnostic pathway 3) Assess cost-effectiveness of the new potential care pathway Methods An open-label, two-arm trial will individually randomise 984 women presenting with suspected UTI to either assessment informed by the PA-100 test or to follow the usual assessment for UTI. The trial is powered on co-primary outcomes of prescription of an antibiotic course for UTI within 28 days from randomisation (superiority), and recovery to only a slight problem or better on day 7 (non-inferiority). Secondary outcomes include: time to symptom resolution, treatment side-effects, antimicrobial resistance, test failures and discordance, adherence, and cost effectiveness. A process evaluation will understand how the test is used and experienced by clinicians and women and how this impacts on behaviour. Timelines for delivery Study duration will be 42 months; 12 months for study set up; pilot trial from month 13 and full trial begins at month 21 if pilot site set up and recruitment criteria are met; last participant in at month 36; with data cleaning, analysis and write-up completed by month 42. 30 General Practice sites will recruit. Anticipated impact and dissemination EVOLUTION will determine whether PA-100 diagnostic guided UTI management in adult women presenting to primary care can safely reduce antibiotic prescribing, which is the information NICE and health systems need to decide whether this potentially transformative technology should be commissioned and taken up into routine care. Findings will inform guidelines and practice in the NHS and world-wide. We will; report findings to the DHSC, NHS, and NICE; present at international conferences; publish findings in pre-prints if appropriate and in first-rank peer-reviewed journals. Patient representatives and charities will help us share our findings with patients, including engaging with the media to facilitate widespread dissemination.