POETIC: Point Of carE Testing for urinary tract Infection in primary Care:
Study Stages 3 & 4: Randomised controlled trial and post-RCT observational study

POETIC is a 4 stage study. This protocol details with stage 3 and 4.

Fifteen percent of community antibiotic prescriptions are for uncomplicated
(lower) urinary tract infections (UTI*s). Optimal diagnostic and management
strategies for these infections remain unclear. The diagnostic accuracy, of
clinical assessment is sub-optimal and as a result many patients are over- or
under- managed.

Primary care clinicians are more likely to treat uncomplicated UTI empirically
(with an antibiotic agent), without additional testing, if women have symptoms
of dysuria and/or frequency. However, 34%- 60% of patients treated with an
antibiotic do not have a microbiologically proven UTI and 25% of those with a
positive culture are not prescribed antibiotics. This is important in terms of
improving outcomes for women with symptoms of UTI. In addition, prescribing
without confirmation of a diagnosis contributes to the growing problem of
antimicrobial resistance.

The overall aim of our study is to evaluate the management of suspected
uncomplicated UTI in women presenting in primary care through use of a novel
point of care test (POCT, Flexicult). This study is being carried out in 4
European networks: Wales, England, Netherlands and Spain and requires a 4 stage
approach. This protocol details with stage 3 and 4.

Within approximately 24 hours the results of this new test will confirm whether
or not there is a bacterial infection, the species involved and its resistance
profile. If there is an infection the GP will be able to prescribe antibiotics
which are most likely to be effective. If no infection is confirmed, the GP can
explain the patient why antibiotics are not indicated. Using this new test is
expected to improve diagnostic accuracy resulting in less under or over of
prescription of antibiotics .

POETIC Stage 3: Randomised controlled Trial
The RCT aims to quantify the effects and costs of an optimised POCT guided
diagnostic and treatment strategy for symptoms of uncomplicated UTI on use of
appropriate antibiotics. 540 adult female patients from the 4 primary care
research networks will be randomised to either the POCT arm or the standard
care (SC) arm. Urine and stool samples will be obtained at presentation
(baseline) and two weeks later. The primary outcome will be appropriate
antibiotic use on day 3 (with day 1 being the day that the patient consulted
with their primary care clinician). Presenting features and management
strategies will be recorded on a case report form by participating clinicians.
Urine samples and stool samples (optional) will be collected from all patients,
and follow-up will be assessed through the use of a patient symptom diary.



POETIC Stage 4: Post- RCT observational phase
There are important questions that require addressing about the uptake of POCTs
in primary care. To answer these a non-randomised pragmatic implementation
study will be performed to evaluate the impact of the optimised POCT diagnostic
strategy in community practice.
Clinicians from approximately 10 general practices per Network (approximately
half of whom participated in the stage 3 RCT) will have the POCT optimised
management strategy available for use at their discretion and will audit their
use of the POCT by recording anonymised data on patients with suspected UTI,
whether or not they used the POCT, and the reasons. A selection of these
clinicians and patients will be interviewed to explore expectations and
experiences regarding POCT use and barriers and opportunities to uptake of the
POCT into routine care.

Participants in stage 3 will be randomised (ratio 1:1) to receive the POCT
management strategy or the standard care (SC) treatment.
Participants randomised to the intervention arm will have their treatment
guided by the Flexicult* POCT. This strategy will be based upon guidelines on
the management of uncomplicated UTI in primary care in participating countries,
and use of a POCT to guide antibiotic management.
The POCT uses a culture-based approach and involves fresh urine being placed on
a special agar plate. The plate is then placed in a simple desktop incubator
within the practice, and read approximately 24 hours later. The plate is
divided into five segments with different antibiotics and special chromatogenic
agar in each segment. This allows for easy assessment of bacterial growth,
evaluation of the species present, enumeration, and assessment of resistance to
a range of antibiotics.
The new Flexicult* plates that will be used have been developed by the
manufacturer (Statens Serum Institut, SSI) and include the antibiotics that are
most commonly used in the 4 European networks: Wales, England, Netherlands or
Spain.
Patients randomised to the control arm will receive standard care.

If patients are assigned to the POCT group (new test), the GP can decide to
follow a symptomatic treatment approach (e.g. to give the patient advice to
take painkillers) until the results of the POCT are known 24 hours later. If
this approach is chosen there is a potential risk the symptoms do not abate
over the 24 hours waiting period or get worse. However, in case the symptoms
get worse or severe symptoms at consultation the GP can advise to start
antibiotics immediately. When the test results become available the GP can
contact the patient to advice whether to continue the treatment, to change
antibiotics or to stop taking the antibiotics .

After patients have given informed consent, some additional information on
symptoms and medical history will be collected. The patient will also be asked
to complete a daily symptom and medication use diary for 2 weeks and send an
additional urine sample* after two weeks. Therefor participation in the study
will take up some additional time.

If patients are randomly assigned to the POCT group (new test), they may be
more likely to receive treatment that is likely to benefit them. In addition,
by participating in this study they are helping to improve the diagnosis and
management of urinary infections, and this may benefit women in the future.

* Patients will also be asked to provide (by post) two stool samples (baseline
& after 2 weeks) to determine the effect of antibiotics on the normal bacteria
found in the gut. Providing these samples is optional.