Title: Catheter Against Urinary Tract Infection Trial: a randomised trial of antimicrobial-impregnated urinary catheters for long-term indwelling urinary catheter users (CAUTI Trial)
Funder: Medical Research Council

Abstract: Background: People with conditions that affect the working of the bladder, such as spinal cord injury or multiple sclerosis, often need to use a catheter for long periods to empty their bladder. People using catheters have a high risk of ‘water infections’, also called a urinary tract infection (UTI). When this happens, people frequently need to have their catheter changed because it becomes blocked, and they often need to take antibiotic tablets. Antibiotics can have unpleasant side-effects such as diarrhoea, and there is a worldwide concern about the overuse of antibiotics and the development of antibiotic-resistant bacteria._x000D_ _x000D_ We have developed a new catheter with three different antibiotics embedded into it that is able to stop bacteria from growing inside it for up to 12 weeks. This should reduce the risk of a urinary tract infection and should also reduce blockages in the catheter. The new catheter might also mean fewer visits to hospital and fewer antibiotic treatments. Our previous small study showed that the catheter is both comfortable and acceptable to long-term catheter users._x000D_ _x000D_ Aims of the research: We will carry out a research study of the new catheter to compare it to a plain catheter, that is the same as the new catheter except that it doesn’t have any antibiotics embedded in it (this is called the ‘control’ catheter). We want to see if the new catheter can reduce urinary tract infections and blockages, as well as hospital visits and antibiotic use. We have consulted our Patient and Public Involvement group and patient support groups to help us plan this study._x000D_ _x000D_ Design and methods: People taking part in the trial will have a 50:50 chance of receiving either the new catheter or the plain one, and they will use these for a year. Each person’s catheter will be changed according to their usual schedule. 274 long-term catheter users will take part in the trial, recruited from eight hospitals in England. Monthly telephone calls to participants will collect information on urinary tract infections, catheter blockages, catheter changes and any side effects from all catheters. Questionnaires will be sent to each participant every three months to collect information on their quality of life and their use of healthcare services._x000D_ _x000D_ An extra small study will also be carried out in two of the hospitals, where the used catheters will be collected and analysed to find out whether they have any antibiotic-resistant bacteria growing inside. In another small study, blood samples will be taken from some people taking part in the study to find out how much of the embedded antibiotics from the new catheter have entered the bloodstream (although in our experience this is likely to be very small amounts). This is to see if the new catheter could affect the body’s normal bacteria._x000D_ _x000D_ Results: The study will find out whether the new catheter can reduce infections and catheter blockages in long-term catheter users. It will also look at the impact of the new catheter on the overall quality of life of those who take part in our study, and whether using the new catheter reduces the need for participants to require prescriptions for antibiotic treatment of urinary tract infections. We will also assess the new catheter for its value for money for the NHS.

Lay abstract: Research question: Does an antimicrobial urinary catheter (AMUC) impregnated with rifampicin, triclosan, and sparfloxacin reduce episodes of catheter-associated urinary tract infection (CAUTI) in long-term catheter users over one year?_x000D_ _x000D_ Background: Patients with long term indwelling urinary catheters are at high risk of repeated CAUTIs. Such infections result in repeated courses of antibiotics and their associated side effects, and there is potential for these infections to lead to additional health issues such as sepsis. Furthermore, all urinary catheters are susceptible to mineral encrustation and blockage, often caused by bacteria, leading to urgent treatment and additional catheterisations. An AMUC with antimicrobial activity for the lifetime of a urinary catheter (up to 12 weeks) has been developed which demonstrates long-term protection in clinically predictive models and fewer bacteria attached to the AMUC than standard catheters on removal in vivo._x000D_ _x000D_ Aims and objectives: We aim to investigate the efficacy, safety, tolerability, and cost effectiveness of the AMUC in reducing the number of CAUTIs over a one year period in long-term catheter users who have a history of recurrent CAUTI. We also aim to carry out two mechanistic sub studies to investigate whether the AMUC does not contribute to the development of antimicrobial resistance. _x000D_ _x000D_ Methods: We will conduct a multicentre, parallel group, randomised controlled trial. Long-term catheter users with a history of recurrent CAUTI (2 episodes of CAUTI in 6 months, or 3 episodes in 12 months) will be broadly eligible for the trial. 274 participants will be randomised to receive either the AMUC or a blinded control catheter, provided in identical packaging, for 12 months, changed according to that participant’s usual schedule. This will allow detection of a change in annual CAUTI rate of 1 per year with 90% power (5% significance level – 2 sided). Allocation will be on a 1:1 basis and conducted via a minimisation algorithm balancing on type of catheter, reason for catheterisation, sex and centre and will include a probabilistic element. Information on episodes of CAUTI, blockage, catheter changes and adverse events will be collected by monthly phone calls to participants. Participants will complete health resource use and quality of life questionnaires every three months._x000D_ _x000D_ One mechanistic sub-study will identify microorganisms attached to AMUCs and control catheters at routine removal and determine their resistance to the three antimicrobials. The other sub-study will analyse a blood sample taken 24 hours post initial catheterisation for the presence of the three antimicrobials by liquid chromatography–mass spectrometry._x000D_ _x000D_ Timelines: Months 1-8: trial set-up and approvals; Months 9-23: Participant recruitment; Month 18: Assessment of progression criteria; Month 35: Follow up for last participant; Months 36-44: data cleaning, data analysis, and dissemination of results._x000D_ _x000D_ Impact and dissemination: Anonymised results will be disseminated to trial participants, relevant patient groups, clinicians, and in academic journals. If the results are positive, we expect to generate patient benefit by reducing infection and associated concerns. This will translate into improved health and quality of life for patients and cost savings to the NHS. We expect to provide a cost effective product to the NHS, and commercialisation by the UK-based partner would contribute to UK economic growth.

Research activity codes: 6.3 MEDICAL DEVICES
Health categories: INFECTION;RENAL AND UROGENITAL