ReSET – Rechallenge Staphylococcus aureus Experimental nasal colonisation sTudy
Staphylococcus aureus nasal colonisation
This study is a two-stage, unblinded, strain-randomised Controlled Human Infection Model (CHIM). It is multicentre, starting in one location with sequential opening of UK locations as required. It is designed to develop and evaluate a safe method of establishing temporary nasal colonisation with Staphylococcus aureus in healthy adults aged 18 to 55 years. In stage I the aim is to find the best challenge dose of up to two strains of S. aureus in order to achieve colonisation in 50 to 70 percent of volunteers. Up to four strains of S. aureus will be trialled and the continuous reassessment method (CRM) will be used to identify the challenge dose. Up to 48 participants per strain will be enrolled. Participants will be screened up to 6 months in advance of enrolment. Screening will involve written consent, a urine test for pregnancy where appropriate, blood tests to check general markers of health, a physical examination and measurement of vital signs. A medical and medication history will be taken. Next of kin information will be requested and they will be provided with a household contact information sheet. Details will also be taken to allow registration on TOPS (trial over-volunteering prevention service) and to allow reimbursement for time and inconvenience. Once enrolled, participants will undergo a 5 day course of standardised decolonisation therapy (nasal antibiotic ointment and antiseptic hair and body wash) starting about 2 weeks before challenge. Participants will have a decolonisation e-diary to record adherence. They will be reviewed about 4 days before challenge for nose samples, body swabs and blood tests. At challenge they will receive a carefully measured dose of liquid containing the candidate strain by dripping it into the nose. The dose will be determined by the continuous reassessment method, which takes into account the proportion of participants colonised up to that point to ensure the best chance of achieving a colonisation rate in the target
1. Adults between 18 to 55 years old (inclusive) at the time of enrolment (defined by the start of first decolonisation therapy) 2. Medically healthy, such that according to investigator judgement, hospitalisation within the study period is not anticipated, and the participant appears likely to be able to remain a study participant through to the end of protocol-specified follow-up. Planned elective procedures for pre-existing conditions may be allowable if S. aureus colonisation is not deemed to put the participant at increased risk of harm and if the elective procedure does not routinely involve, and is not likely to involve, decolonisation and/or antibiotic therapy 3. Fluent spoken English – to ensure a comprehensive understanding of the research project and their proposed involvement 4. Capacity to provide written informed consent in English for participation in the study 5. Able to attend the scheduled visits and to comply with all study procedures, including internet access for the recording of electronic diaries after issue of decolonisation therapy and S. aureus challenge 6. Able to follow and adhere to hygiene advice as well as the decolonisation protocol which includes daily shower and hair wash 7. Willing and able to avoid planned, non-essential non-study antibiotics for the duration of the study 8. Willing and able to avoid intranasal and inhaled products (including nasal steroids) unless prescribed by the study team for the duration of the study 9. Able to adhere to standard hygiene advice at home 10. Willing to allow confirmation of past medical history either through provision of, or access to, a medical record summary or other medical documentation or to allow investigators to obtain a copy of their medical history via their GP practice or via electronic patient records 11. Willing to allow their GP and/or consultant, if appropriate, to be notified of participation in the study 12. Willing to provide their national insurance number or passport numb
1. Research participants 1.1. Participation in another research study in which procedures could compromise the integrity of this study (for example immune modulating or stimulating treatments) or the safety of the participant (for example significant volumes of blood taken), or planning to do so within the study period 2. Vaccination (self-reported with or without confirmation from GP questionnaire or medical records or summary if deemed necessary at clinician discretion) 2.1. Planned vaccination in the two months following final challenge 2.2. Live vaccination within the 4 weeks prior to first challenge 3. Allergy 3.1. Have an allergy or intolerance to beta-lactam antibiotics 3.2. Have an allergy or intolerance to more than one of doxycycline, co-trimoxazole, clindamycin and linezolid 3.3. Have an allergy or intolerance to any of the agents used for decolonisation 4. Specific health history (self-reported with or without confirmation from GP questionnaire or medical records or summary if deemed necessary at clinician discretion) 4.1. History of severe S. aureus infection, including PVL-associated disease 4.2. Atopic dermatitis 4.3. Psoriasis, eczema or other chronic skin condition requiring treatment in the last year 4.4. Compromised skin barrier function at the discretion of the investigator 4.5. Known structural heart issues at the discretion of the investigator, including but not limited to PFO, VSD and bicuspid AV 4.6. Implanted prosthetic material including but not limited to cochlear implants, orthopaedic implants, implantable cardiac devices, cardiac valves and neurological stimulators 4.7. Recurrent sinusitis 4.8. Previous sinus surgery 4.9. Planned surgical, dental, orthodontic, dental hygienist or pre-operative appointment over the study period 5. General health history (self-reported and or confirmed from GP questionnaire or medical records or summary if deemed