Title: A multi-centre randomised controlled non-inferiority and cost effectiveness trial comparing Polyhexanide and Chlorhexidine with Neomycin to Mupiricon for nasal meticillin-resistant Staphylococcus aureus (MRSA) decolonisation amongst adult hospital in-patients
Funder: Department of Health and Social Care

Abstract: Bacteria such as Staphylococcus aureus (S. aureus) live on and around us without causing harm. But patients coming into hospital who carry S. aureus in the nose and skin are at increased risk of developing infections if the bacteria get access to areas such as the site of surgery or a drip to give fluid or drugs. These infections are difficult to treat when a resistance to penicillin has built up, known as meticillin-resistant Staphylococcus aureus (MRSA). To reduce the risk of getting an infection while in hospital, many patients are routinely “decolonised” of the S. aureus bacteria. This usually involves the patient applying a nasal ointment, mupirocin (a type of antibiotic), three times daily for five days and using a body wash._x000D_ _x000D_ However, there are growing concerns that some S. aureus is also resistant to mupirocin, so it is not good to be relying on a single treatment. In this study we will look at two alternatives to find out if they are as effective as mupirocin. Adult hospital inpatients who are found to carry MRSA following a routine screening swab on hospital admission will be invited to take part in the study. Patients who consent to take part will be put in one of three groups. One group will be given the usual treatment of nasal mupirocin, the second will use nasal polyhexanide gel (an antiseptic) and the third group, nasal neomycin cream (an antibiotic). This will be a randomised study and neither the patient nor the clinician will choose the group to ensure a fair comparison between the treatments. All three groups will also be given chlorhexidine for washing/showering for five days. We will then collect the results from a repeat nasal swab taken 48 hours after they finish treatment. Our measure of whether the proposed alternative treatments work as well as mupirocin will be the number of successful nasal decolonisations._x000D_ _x000D_ The study will take place in NHS hospitals. We aim to recruit 3,000 participants. The different treatments are already used in the NHS but how well they work for nasal decolonisation of MRSA is not clear. Patients will be recruited from those whose swabs are positive for MRSA when taken for routine screening of in-patients on admission. MRSA swabs will be taken 48 hours after treatment has finished. Patients will be rescreened 4 weeks later._x000D_ _x000D_ We have consulted with our Patient and Public Involvement (PPI) co-applicant, from MRSA Action UK, and as an advisor for the project, she will help us get a wider public perspective through members of MRSA Action UK and development of a project specific panel. We have been told that the research team need to be aware during recruitment that patients may already be confused and frightened at being told they are colonised with MRSA. MRSA Action UK have experience producing patient and carer information for their website and will contribute to patient-facing materials such as recruitment materials. We plan to include participants who are unable to give consent for themselves, for example people with dementia. This is a vulnerable group, but it will be really important to ensure they are included as they make up a large proportion of those at risk. We have included costs for PPI involvement in our budget._x000D_ _x000D_ The results will be shared throughout the NHS, charities and those who write guidelines for doctors. We will write a summary of the results for patients, families, carers and all those who help deliver the trial in NHS hospitals.

Lay abstract: Background_x000D_ Staphylococcus aureus (S. aureus) is a leading cause of hospital-acquired infections. These infections are difficult to treat when there is evolved resistance to penicillin, known as meticillin-resistant Staphylococcus aureus (MRSA). Patients who carry S. aureus in the nose and skin are prone to developing infections and many patients admitted to hospital are routinely “decolonised" to reduce this risk. The current standard treatment for nasal decolonisation is the antibiotic nasal mupirocin. There are concerns about over-reliance on a single treatment and the risk of mupirocin resistant MRSA. Robust evidence for alternatives to mupirocin is required._x000D_ _x000D_ Aims and objectives_x000D_ We aim to investigate whether there are effective and cost-effective alternatives to mupirocin for early nasal decolonisation of MRSA amongst adult hospital in-patients._x000D_ _x000D_ The objectives are to undertake:_x000D_ (i) A multi-centre, three-arm parallel group, non-inferiority randomised controlled trial to determine whether nasal polyhexanide gel (an antiseptic) or chlorhexidine with neomycin cream (an antibiotic) plus chlorhexidine body wash is not inferior to nasal mupirocin ointment plus chlorhexidine body wash for early nasal decolonisation of MRSA amongst adult hospital in-patients._x000D_ (ii) A 9-month internal pilot to confirm trial feasibility_x000D_ (iii) An analysis of secondary outcomes_x000D_ (iv) A cost-effectiveness analysis of the three interventions from the NHS perspective_x000D_ _x000D_ Methods_x000D_ Adult hospital in-patients identified as being colonised with MRSA on routine hospital admission screening will be eligible for inclusion. The primary outcome is successful early nasal decolonisation defined as a negative nasal swab 48 hours following completion of decolonisation treatment. Secondary outcomes include treatment acceptability and adverse events at the primary follow-up point and successful late nasal decolonisation, mortality, MRSA infections and length of stay at 4 weeks following treatment completion. Decolonisation of MRSA not fully susceptible to mupirocin and resistance to mupirocin and other antimicrobials of post-colonisation isolates will be assessed. The cost-effectiveness analysis will follow a modelling approach, developing a comprehensive model that brings together all available evidence using a lifetime time horizon._x000D_ _x000D_ A 9-month internal pilot will assess assumptions about site set up, participant recruitment and completeness of follow-up. 3,000 patients will be recruited to provide 90% statistical power to establish non-inferiority of each intervention compared with mupirocin within a margin of 6% in successful early nasal decolonisation, assuming 10% attrition at follow-up 48 hours following completion of decolonisation treatment._x000D_ _x000D_ Timelines for delivery_x000D_ The study will be 39 months’ duration: study set-up 8 months; internal pilot 9 months; recruitment for main trial 15 months; final follow-up 1 month; statistical analysis and write-up 6 months. _x000D_ _x000D_ Anticipated impact and dissemination_x000D_ Depending on the results, the study has the potential to widen the recommended treatment options for nasal decolonisation of MRSA and reduce reliance on mupirocin. Targets for dissemination include NICE, hospital infection prevention specialists and hospital pharmacists. The study protocol and results will be presented orally and published in journals and results will be made available in plain English for patient-focused dissemination.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: INFECTION