Condition category
Infections and Infestations
Date applied
11/02/2015
Date assigned
11/02/2015
Last edited
17/10/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

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

Trial website

http://www.southampton.ac.uk/ctu/trialportfolio/listoftrials/atafutitrial.page?

Contact information

Type

Scientific

Primary contact

Mrs Catherine Simpson

ORCID ID

Contact details

University of Southampton
Southampton Clinical Trials Unit
MailPoint 131
Tremona Road
Southampton
SO16 6YD
United Kingdom

Additional identifiers

EudraCT number

2013-003327-11

ClinicalTrials.gov number

Protocol/serial number

3623

Study information

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

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

14/SC/1143; First MREC approval date 22/09/2014

Study design

Randomised; Interventional and Observational; Design type: Treatment, Qualitative

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

GP practices

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details to request a patient information sheet

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

Phase

Phase III

Drug names

Primary outcome measures

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 trial start date

01/04/2015

Overall trial end date

31/05/2017

Reason abandoned

Eligibility

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 type

Patient

Age group

Adult

Gender

Female

Target number of participants

Planned Sample Size: 376; UK Sample Size: 376

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

United Kingdom

Trial participating centre

Abbeywell Surgery
SO51 8QN

Trial participating centre

The Adam Practice
BH15 4JQ

Trial participating centre

Bere Regis Surgery
BH20 7HB

Trial participating centre

Bosmere Medical Practice
PO9 1DQ

Trial participating centre

Cowplain Family Practice
PO8 8DL

Trial participating centre

Friarsgate Practice
SO22 6EL

Trial participating centre

Highcliffe Medical Centre
BH23 5ET

Trial participating centre

Liphook & Liss Surgery
GU32 2BL

Trial participating centre

Oaklands Practice
GU46 7LS

Trial participating centre

Portsdown Group Practice
PO4 0DY

Trial participating centre

Rowlands Castle Surgery
PO9 6BN

Trial participating centre

The Three Swans Surgery
SP1 1DX

Trial participating centre

Wareham Surgery
BH20 4PG

Trial participating centre

Woolston Lodge Surgery
SO19 9AL

Trial participating centre

Forest End Surgery
PO7 7AH

Trial participating centre

Swanage Medical Centre
BH19 1HB

Trial participating centre

Pioneer Medical Group
BS10 6SP

Trial participating centre

Brockway Medical Centre
BS48 1BZ

Trial participating centre

Churchdown Surgery
GL3 2DB

Trial participating centre

Coleridge Medical Centre
EX11 1EQ

Trial participating centre

Combe Down Surgery
BA2 5EG

Trial participating centre

Crown Medical Centre
TA2 8QY

Trial participating centre

Grange Road Surgery
BS13 8LD

Trial participating centre

Hawthorne Medical Centre
SN2 1UU

Trial participating centre

Kingswood Health Centre
BS15 4EJ

Trial participating centre

Mendip Vale Medical Practice
BS49 4ER

Trial participating centre

Nightingale Valley Practice
BS4 4HU

Trial participating centre

Portland Practice
GL50 4DP

Trial participating centre

Rame Group Practice
PL11 2TB

Trial participating centre

Rolle Medical Partnership
EX8 2JF

Trial participating centre

The Avenue Surgery
BA12 9AA

Trial participating centre

Vine Surgery
BA16 0ET

Trial participating centre

Wells City Practice
BA5 1XJ

Trial participating centre

The Wellspring Surgery
BS5 9QY

Trial participating centre

Westbury on Trym Primary Care Centre
BS9 3AA

Trial participating centre

The Boathouse Surgery
RG8 7DP

Trial participating centre

Bridge Street Medical Centre
CB2 3LS

Trial participating centre

Broadshires Health Centre
OX18 1JA

Trial participating centre

Brockwood Medical Practice
RH3 7NJ

Trial participating centre

Hightown Surgery
OX16 9DB

Trial participating centre

Hollow Way Medical Centre
OX4 2NB

Trial participating centre

The Ivers Practice
SL0 9NU

Trial participating centre

Kingswood Surgery,
HP13 7UN

Trial participating centre

Leighton Road Surgery
LU7 1LB

Trial participating centre

Montgomery House Surgery
OX26 6HT

Trial participating centre

St Clement’s Surgery
OX4 1JS

Trial participating centre

Temple Cowley Medical Group
OX4 2HL

Trial participating centre

Wymondham Medical Practice
NR18 0RF

Sponsor information

Organisation

University of Southampton

Sponsor details

Building 37
Highfield
Southampton
SO17 1BJ
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

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.

Intention to publish date

01/05/2017

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

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'.