Defining best Management in Adult Chronic RhinOsinusitis (MACRO): a randomised controlled trial
Rhinosinusitis
The MACRO Trial will investigate three different treatment options for patients with CRS. All participants who join the MACRO Trial will be asked to use standard care (intranasal medications), which are considered the current best practice for management of CRS. This intranasal medication includes nasal steroid drops/sprays and saline rinses. The trial incorporates an internal pilot recruitment phase (first 6 months at 6 sites) with an embedded MACRO Conversation Study, before progressing to the full trial phase (a further ~11 sites). INTERNAL RECRUITMENT PILOT PHASE (INCLUDING MACRO CONVERSATION STUDY) The aim of the internal recruitment pilot phase is to randomise 72 participants at 6 pilot sites within 6 months. At least 3 sites should be open for the 6 month internal recruitment pilot phase to begin. Recruitment will be deemed successful if ≥75% of expected, i.e. 54 patients are recruited. A MACRO Conversation Study will be conducted as part of the pilot phase to identify any challenges to recruitment so that suggestions can be made to change aspects of design or conduct, recruitment strategies can be implemented and any training can be delivered to aid improvements in recruitment for the main trial phase. If recruitment is less than expected, we will propose a plan to increase recruitment based on the findings from the MACRO Conversation Study and communicate regularly with the funder. MAIN TRIAL PHASE On the basis of the pilot phase being successful, a further pre-identified 11 sites will be opened, and all 17 sites will recruit the remaining participants required to achieve a sample size of 600 within the funded timescale of the MACRO trial (estimated total trial duration is 52 months). RECRUITMENT OF PATIENTS The research nurse (RN) at each site will screen referral letters for adult patients with suspected CRS, coming from either primary care clinicians or secondary care colleagues. Where possible, these patients will be booked into MACRO outpatient
Current inclusion criteria as of 13/09/2022: 1. Adults aged 18 and over with a diagnosis of CRS according to European guidelines: A minimum of 12 weeks history of inflammation of the nose and paranasal sinuses characterised by two or more symptoms, one of which should be either nasal blockage/obstruction/ congestion or nasal discharge (anterior/posterior nasal drip): ± facial pain/pressure ± reduction or loss of smell 2. Nasal endoscopy (within last 3 months) to determine CRS diagnosis and phenotype (CRSwNPs or CRSsNPs) 3. Non-contrast CT scan (within last 18 months) to determine Lund-Mackay score and confirm suitability for ESS 4. Moderate/severe symptoms; SNOT-22 score ≥ 20 (within last 3 months) 5. Symptom control not achieved following previous Appropriate Medical Therapy (AMT), as deemed by the local Principal Investigator (PI) or Co-Investigator (Co-I), and therefore considered eligible for ESS 6. An understanding of the English language sufficient to understand written and verbal information about the trial, its consent process and the study questionnaires Previous inclusion criteria: 1. Adults aged 18 and over with a diagnosis of CRS according to European guidelines: 1.1. A minimum of 12 weeks history of inflammation of the nose and paranasal sinuses characterised by two or more symptoms, one of which should be either nasal blockage/obstruction/ congestion or nasal discharge (anterior/posterior nasal drip): 1.1.1. ± Facial pain/pressure 1.1.2. ± Reduction or loss of smell 2. Nasal endoscopy (within last 3 months) to determine CRS diagnosis and phenotype (CRSwNPs or CRSsNPs) 3. Non-contrast CT scan (within last 12 months) to determine Lund-Mackay score and confirm suitability for ESS 4. Moderate/severe symptoms; SNOT-22 score ≥ 20 within last 3 months 5. Symptom control not achieved following previous AMT, as deemed by the local Principal Investigator (PI) or Co-Investigator (Co-I), and therefore considered eligible for ESS 6. An understanding of the Englis
Current exclusion criteria as of 13/09/2022: 1. Lund-Mackay non-contrast CT scan score <4 2. Macrolide antibiotic treatment for >3 continuous weeks’ duration within the last 12 months 3. ESS in the previous 6 months or visible fronto-ethmoidal, open sinus cavities (including Draf III/modified Lothrop) from previous surgery 4. Oral/IV/Depot steroids within one month of baseline visit 5. Active treatment with biologic therapies which may modulate disease severity in CRS 6. Rare/complex sinus conditions: 6.1. CRS secondary to systemic disease - cystic fibrosis, granulomatous diseases 6.2. Suspected malignancy 7. Allergic fungal rhinosinusitis confirmed or suspected on CT imaging (expansion and mixed density opacification) necessitating immediate surgery 8. Severe asthma (high doses of inhaled steroids i.e. >1.5 mg per day) 9. Females who are pregnant or breastfeeding, females of reproductive potential not prepared to use a reliable means of contraception (e.g. hormonal contraceptive patch, intrauterine device, physical barrier or abstinence, if preferred and usual lifestyle of the patient) at trial entry or those females wanting to start a family during the initial 3 months of the trial 10. Known immunodeficiency states including HIV and selective and multiple antibody deficiency states 11. Severe septal deviation preventing endoscopic examination 12. Contraindications to surgery (significant medical co-morbidity) 13. Any absolute contraindications to clarithromycin (risk factors to be assessed at screening include a history of ischaemic heart disease, prolonged Q-T interval on ECG, or any medications known to interact with clarithromycin unless these can be discontinued during the 3 months of clarithromycin/placebo treatment, see appendix 5) 14. Known allergies to the IMP and excipients of IMP and placebo 15. Inability to give consent (significant cognitive impairment or language issues) or to understand and comply with trial instructions 16. Participation in another