Urinary tract infections (UTI), cystitis, pyelonephritis Urological and Genital Diseases
Conditions
Interventions
Cystitis interventions: participants will be randomised to nitrofurantoin or pivmecillinam (1:1), and subsequently randomised to one of five antibiotic durations: one, two, three, four or five days (1
Sponsors
University of Oxford
Eligibility
Sex/Gender
Female
Inclusion criteria
Inclusion criteria: 1. Female, aged 18 years or above 2. Participant is willing and able to give informed consent for participation in the trial. 3. Urine sample for culture has been/can be obtained prior to starting antibiotics 4. For pyelonephritis sub trial (primary and secondary care): 4.1. Presenting with acute pyelonephritis symptoms for which the responsible clinician considers antibiotic treatment is either indicated or for whom an antibiotic has already been started within the previous 48 hours. 4.2. Temperature of >38.0oC measured at presentation AND loin/flank pain or costovertebral angle tenderness AND =1 symptom of acute UTI (frequency, dysuria, urgency, nocturia, change in urine smell or appearance (e.g. cloudy or bloody urine), suprapubic pain). 4.3. If recruited in secondary care, willing to allow their General Practitioner, to be notified of participation in the trial 5. For the cystitis sub trial (primary care only): 5.1. Presenting with acute cystitis symptoms for which the responsible clinician consider antibiotic treatment is indicated 5.2. =two of the following symptoms of acute UTI (frequency, dysuria, urgency, nocturia, change in urine smell or appearance (e.g. cloudy or bloody urine), suprapubic pain). 6. English speaking
Exclusion criteria
Exclusion criteria: 1. Antibiotics for the prevention or treatment of UTI within the previous month (n.b. Pyelonephritis patients that have started antibiotics within 48 hours are included). 2. Previous participation in the DURATION UTI Trial 3. Indwelling catheter 4. Inclusion in the trial is inappropriate in the judgement of the responsible clinician 5. Known anatomical abnormality of the urinary tract 6. Neurogenic bladder 7. Known pregnancy (pregnancy test not required for participation) 8. Unable to comply with study procedures 9. All antibiotic agents available to the participant in the trial are precluded in the view of the responsible clinician for example by: 9.1. patient factors (such as allergy, degree of renal impairment) 9.2. antibiotic susceptibility results (e.g. known carrier of antibiotic resistant organisms or resistance profile of the current infection if known at randomisation).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of participants in each arm experiencing sustained clinical cure without medically attended symptomatic recurrence through to day 42. Defined as no contact with a healthcare provider for UTI symptoms between randomisation and day 42. For patients recruited during a hospital admission for UTI, healthcare contacts will only be included in this definition if they are for new or worsening symptoms of UTI. Measured using records review and patient report. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Daily through to day 42 measured using patient reported seven-point symptom severity scale, ranging from 0 (no problem) to 6 (as bad as it could be), participants will record the severity of several common presenting symptoms of urinary tract infection. 1.1. At day 42 measured using patient reported seven-point symptom severity scaleDuration of moderately bad (symptom severity score 3) and/or worse symptoms (symptom severity score 4-6) - measured using a patient-reported seven-point symptom severity score ranging from: 0 (no problem), 3 (moderately bad), 6 (as bad as it could be). 1.2. Total duration of symptoms – using the symptom severity scale described above, we will define the first day on which all symptoms are scored 0 as the day of complete symptom resolution. 1.3. Worsening or progression of symptoms 2.1. Number of symptomatic recurrences – defined as per our primary outcome definition; 2.2. Number of hospitalisations/prolonged hospitalisation/readmission for the treatment of urinary tract infection, urosepsis or a drug-related adverse event measured using records review and patient report at day 42 3. Frequency of adverse antibiotic effects (diarrhoea, nausea/loss of appetite, skin rash) measured using symptom diary, and records review at day 42 4. Total quantity of antibiotic use for the treatment of UTI including any non-NHS prescription usage measured using records review and patient report at day 42 4.1. Courses 4.2. days of treatment 4.3. total defined daily doses 5. Number of microbiological treatment failures 2 days after end of treatment measured through culture of a urine sample provided by all study participants 6. Resistance profile of urine culture isolates obtained from participants who experience treatment failure through to day 42 compared with baseline samples measured though culture of urine samples provided by participants alongside any urine samples they submit for clinical purposes during follow up period. 7. Measured and reported | — |
Countries
United Kingdom
Outcome results
None listed