Alternative treatments of adult female urinary tract infection
| ISRCTN | ISRCTN43397016 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN43397016 |
| EudraCT/CTIS number | 2013-003327-11 |
| Secondary identifying numbers | 3623 |
- Submission date
- 11/02/2015
- Registration date
- 11/02/2015
- Last edited
- 29/01/2019
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English Summary
Background and study aims
Antibiotic resistance is rising and linked to prescribing in primary care (for example, by GPs). It is a national priority to try to reduce antibiotic prescribing where possible and resistance to antibiotics is a particular problem with cystitis (urinary tract infection). Cystitis in adult women is one of the most common conditions treated with antibiotics in primary care. Although the symptoms are distressing, symptoms usually settle without complications within a few days. Antibiotics do shorten the duration of symptoms and treatment is currently the norm. An alternative strategy to delay the prescription of antibiotics for a few days has been successful in respiratory (lung) infections. In cystitis this results in a modest reduction in antibiotic prescribing but slightly prolonged symptoms. It is unlikely however that the delayed prescribing strategy will be widely adopted unless an alternative approach for symptom relief is available. Two candidates for symptom relief have been identified: anti-inflammatory drugs (ibuprofen) and a herbal product (Arctostaphylos Uva ursi). This study aims to find out whether Uva ursi and/or advice to take ibuprofen would relieve the symptoms of cystitis during the period of delayed treatment. If so, the results would have the potential to change practice and to promote a delay in antibiotic prescribing in primary care, resulting in a reduction of antibiotics being prescribed.
Who can participate?
Women aged between 18 and 70, presenting to their GP with suspected cystitis
What does the study involve?
Participants are asked to accept a delayed prescription for antibiotics and then are randomly allocated into one of four groups: Group 1: Uva Ursi + advice to take ibuprofen; Group 2: Uva Ursi placebo (dummy drug) + advice to take ibuprofen; Group 3: Uva Ursi + no advice to take ibuprofen; or Group 4: Uva Ursi placebo + no advice to take ibuprofen. If their symptoms get worse or have not improved after 3-5 days participants start taking antibiotics. Severity of symptoms is recorded using a diary and the proportion of women using antibiotics in each group is measured.
What are the possible benefits and risks of participating?
It is not known whether the patients will have any personal benefit from taking part in this study. However, their participation may help to give important information about how best to treat people with cystitis in the future. Patients would, if required, normally start taking an antibiotic prescription immediately to relieve their symptoms. In this study participants have a 1 in 4 chance of receiving no symptom relief treatment. It is possible that the uncomfortable symptoms of urinary tract infection may last longer. A prescription for antibiotics will be available should the participant wish to start taking them. Very rarely untreated urinary infection can spread to the kidneys. If this happens the participant would become more unwell and develop back pain, high fever and vomiting. A kidney infection needs urgent treatment and participants will be advise to contact their doctor if any of these symptoms develop. Also it is not known to which group participants will be allocated so it will be necessary for them to avoid taking any additional anti-inflammatories, such as Nurofen, whilst they are taking the study medication.
Where is the study run from?
University of Southampton, Southampton Clinical Trials Unit (UK)
When is the study starting and how long is it expected to run for?
July 2012 to May 2017
Who is funding the study?
National Institute for Health Research (UK), School of Primary Care
Who is the main contact?
Mrs Catherine Simpson
Contact information
Scientific
University of Southampton
Southampton Clinical Trials Unit
MailPoint 131
Tremona Road
Southampton
SO16 6YD
United Kingdom
Study information
| Study design | Randomised; Interventional and Observational; Design type: Treatment, Qualitative |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | GP practice |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a patient information sheet |
| Scientific title | Alternative Treatments of Adult Female Urinary Tract Infection: a double-blind, placebo-controlled, factorial randomised trial of Uva ursi and open pragmatic trial of ibuprofen |
| Study acronym | ATAFUTI |
| Study hypothesis | Current hypothesis as of 13/09/2016: Does Uva ursi (a herbal product) or advice to take a NSAID provide relief from urinary symptoms and reduce antibiotic use in adult women with suspected cystitis who accept the delayed prescription strategy. Previous hypothesis: ATAFUTI is a Phase III double blind, placebo controlled, factorial randomised trial investigating alternative treatments for adult female urinary tract infections (UTI). |
| Ethics approval(s) | 14/SC/1143; First MREC approval date 22/09/2014 |
| Condition | Topic: Primary Care; Subtopic: Infectious diseases and microbiology, Primary care; Disease: All Diseases |
| Intervention | Current interventions as of 13/09/2016: Participants are asked to accept a delayed prescription for antibiotics and then are randomly allocated into one of four groups: Group 1 – Uva Ursi 1200mg tds + advice to take ibuprofen Group 2 – placebo tds + advice to take ibuprofen Group 3 – Uva Ursi 1200mg tds + no advice to take ibuprofen Group 4 - placebo tds + no advice to take ibuprofen. If their symptoms get worse or have not improved after 3-5 days participants will start taking their antibiotics. Severity of symptoms is recorded using a diary and the proportion of women using antibiotics in each group measured. Follow Up Length: 3 month(s); Study Entry : Single Randomisation only Previous interventions: 1. Ibuprofen, 400mg tds 2. Placebo, tds 3. Uva ursi, 1200mg tds Follow Up Length: 3 month(s); Study Entry : Single Randomisation only |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | |
| Primary outcome measure | Symptom severity day 2-4 using validated diary data |
| Secondary outcome measures | Current secondary outcome measures as of 19/09/2016: 1. Use of antibiotics - participant records in their diary if they took the antibiotics prescribed at the time of their initial consultation. 2. Duration of moderately bad symptoms – patients record the severity of a range of urinary symptoms on a daily basis using a validated scoring system from the day of randomisation until all symptoms have resolved. The symptoms are: fever, pain in the side, blood in urine, smelly urine, burning (burning or pain when passing urine), urgency (having to go in a hurry), day time frequency (having to go more often than usual during the day), night time frequency (having to go more often than usual during the night), tummy pain (when not passing urine), restricted activities, unwell. The scoring system is: 0 = Normal/not affected, 1 = Very little problem, 2 = Slight problem, 3 = Moderately bad, 4 = Bad, 5 = Very bad, 6 = As bad as it could be 3. Total symptom burden derived from diary data 4. Re-consultation in 1 month with UTI from notes review 5. Re-consultation in 3 months with UTI from notes review Previous secondary outcome measures: 1. The use of antibiotics – whether the participant had to use the delayed prescription given to them by the GP at the time of their initial consultation when they were randomised to the trial. This will be recorded in their participant diary 2. Duration of moderately bad symptoms – patients record the severity of a range of urinary symptoms on a daily basis using a validated scoring system from the day of randomisation until all symptoms have resolved. The symptoms are: fever, pain in the side, blood in urine, smelly urine, burning (burning or pain when passing urine), urgency (having to go in a hurry), day time frequency (having to go more often than usual during the day), night time frequency (having to go more often than usual during the night), tummy pain (when not passing urine), restricted activities, unwell. The scoring system is: 0 = Normal/not affected, 1 = Very little problem, 2 = Slight problem, 3 = Moderately bad, 4 = Bad, 5 = Very bad, 6 = As bad as it could be 3. Re-consultation with UTI within the 3-month period following randomisation. This will be determined at the 3 months note review carried out by the GP 4. Exploratory Analysis: Differential effects on primary outcome depending on urinary culture results |
| Overall study start date | 01/04/2015 |
| Overall study end date | 31/05/2017 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 70 Years |
| Sex | Female |
| Target number of participants | Planned Sample Size: 376; UK Sample Size: 376 |
| Participant inclusion criteria | 1. Adult women (18-70) presenting to primary care with suspected lower urinary tract infection i.e. with at least one of dysuria, urgency or frequency 2. Patient able to provide informed written consent 3. Women willing to accept a delayed prescription for antibiotics |
| Participant exclusion criteria | Current exclusion criteria as of 13/09/2016: 1. Known or suspected pregnancy or breast feeding. In women of child bearing age a urine pregnancy test will usually be performed unless not indicated (for instance prior hysterectomy) 2. Known immunodeficiency state, long term corticosteroids therapy or chemotherapy 3. Diabetes 4. Has any of the following known contraindications or cautions to Ibuprofen and any as listed in the current SmPC: 4.1. Asthmatics sensitive to NSAIDS/Ibuprofen or Aspirin 4.2. Severe heart failure and uncontrolled hypertension 4.3. Active gastrointestinal ulceration or bleeding 4.4. Crohn’s disease or ulcerative colitis 4.5. Documented poor renal function 4.6. Chronic Kidney disease (Grade 3-5) 5. Currently or within 7 days taken antibiotics 6. Using a NSAID or Uva Ursi preparation and unwilling to discontinue for the study period 7. Suspected upper urinary tract infection (back pain, high fever>38C, systemic illness) 8. Women whom immediate antibiotics are otherwise indicated frequent recurrent infection: >3 UTI episodes in past 12 months 9. Defect of the blood clotting system 10. Bladder surgery including cystoscopy in the last four weeks 11. Currently taking Warfarin 12. Recruited to another interventional trial in previous 6 weeks Previous exclusion criteria: 1. Known or suspected pregnancy or breast feeding. In women of child bearing age a urine pregnancy test will usually be performed unless not indicated (for instance prior hysterectomy) 2. Known immunodeficiency state, long term corticosteroids therapy or chemotherapy 3. Diabetes 4. Has any of the following known contraindications or cautions to Ibuprofen and any as listed in the current SmPC: 4.1. Asthmatics sensitive to NSAIDS/Ibuprofen or Aspirin 4.2. Severe heart failure and uncontrolled hypertension 4.3. Active gastrointestinal ulceration or bleeding 4.4. Crohn’s disease or ulcerative colitis 4.5. Documented poor renal function 4.6. Chronic Kidney disease 5. Currently or within 7 days taken antibiotics 6. Using a NSAID or Uva Ursi preparation and unwilling to discontinue for the study period 7. Suspected upper urinary tract infection (back pain, high fever>38C, systemic illness) 8. Women whom immediate antibiotics are otherwise indicated frequent recurrent infection: >3 UTI episodes in past 12 months 9. Defect of the blood clotting system 10. Bladder surgery including cystoscopy in the last four weeks. 11. Currently taking Warfarin 12. Recruited to another trial in previous 4 weeks. |
| Recruitment start date | 01/08/2015 |
| Recruitment end date | 21/10/2016 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
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Sponsor information
University/education
Building 37
Highfield
Southampton
SO17 1BJ
England
United Kingdom
"ROR" |
https://ror.org/01ryk1543 |
|---|
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/05/2017 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | It is intended that the results will be published in the following but there are no definite dates for this: 1. Peer-reviewed scientific journals 2. Internal report 3. Conference presentation 4. Publication on website |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 08/09/2017 | Yes | No | |
| Results article | results | 01/08/2019 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
29/01/2019: Publication reference added.
12/09/2017: Publication reference added.
17/10/2016: The recruitment end date was changed from 30/09/2016 to 21/10/2016.
13/09/2016: The following changes were made to the trial record:
1. The scientific title was changed from 'Alternative Treatments of Adult female Urinary Tract infection: a double-blind randomised controlled trial' to 'Alternative Treatments of Adult Female Urinary Tract Infection: a double blind, placebo controlled, factorial randomised trial of Uva ursi and open pragmatic trial of ibuprofen'.
2. The overall trial end date was changed from 31/12/2015 to 31/05/2017.
3. The target number of participants was changed from 'Planned Sample Size: 600; UK Sample Size: 600' to 'Planned Sample Size: 376; UK Sample Size: 376'.
