Title: NAIROS - Nasal AIRway Obstruction Study
Funder: Department of Health and Social Care

Abstract: Design: A mixed methods study, informed by an already executed feasibility phase, incorporating: Fast-track Start-up; Internal Pilot; multicentre trial with qualitative process and economic evaluation, randomising patients to immediate septoplasty versus non-surgical management. NAIROS is powered to detect a clinically meaningful difference at 6 months and maps outcomes to baseline severity [Nasal Obstruction Symptom Evaluation (NOSE) Scale]. Treatment allocation by random permuted blocks, stratified by gender and severity Setting: 16 Ear Nose and Throat outpatient clinics, district and teaching hospital in Scotland and England Target Population: 378 adults referred to secondary care with reduced nasal airway and a deviated nasal septum at nasendoscopy. Health Technologies Assessed: Closed septoplasty, within 2 months, +/- reduction of the inferior turbinate on concave side. Conservative management. Aligned with patient preference, and preparatory work with both patients and Primary Care clinicians, NAIROS standardised medical therapy is a twice daily dose of each of a saline spray and fluorinated steroid spray, for 6 months. Our mixed method process evaluation will identify, describe, understand and address: a) Factors influencing trial participation including willingness to randomise and be randomised b) Experiences of study interventions and process c) Factors likely to influence wider implementation of study findings. Measurement of costs and outcomes Internal pilot N screened, n randomised in 6 months, extent and causes of ineligibility/ non-consent Distributions of eligible and participating patients across baseline severity spectrum Main trial Primary outcome SNOT-22 score, recorded at 6 & 12 months post randomisation mapped to baseline severity, stratified by gender Secondary outcomes recorded at baseline, 6 and 12 months SNOT-22 subscales; NOSE scale; Quality of life – SF-36 Rhinospirometry - right and left nasal airflow plus Nasal Partitioning Ratio (NPR); Double Ordinal Airway Subjective Scale. Adverse events, serious adverse events and need for additional interventions (primary and secondary care) Economic outcomes – Incremental cost per 1. Change in SNOT-22 2. QALY gained 3. Adverse event avoided Costs to NHS and patients at 12 months Longer term economic model Overall Final outcome - Generation of NHS Guidance NAIROS models clinical and economic outcome against baseline severity on the NOSE scale, taking account of gender and concomitant turbinate reduction, hence generates the best possible NHS evidence-based guidance. Sample size: Recruitment target = 378 patients, allowing 20% attrition, 90% power to show a minimum clinically important (9-point) difference in 6-month primary outcome between randomised treatment groups, allowing p=0.05, effect size 0.38 Project Timeline (Months) -3 to 3 Fast-track start-up; MACRO database construction; www.NAIROS.co.uk populated; first DMC and Launch month 4 10 site initiation visits (including Newcastle). Trial Launch Meeting. 5-9 internal pilot. 2 months to recruit 2 patients at each site; 3 months at full recruitment rate 2 / month = 8/ site X 10 sites = 80 total pilot phase recruits 10- 24 main trial recruitment, 16 sites total 20 per month x15 months; n = 300 25- 30 final interventions 30- 36 follow-up completed 37- 42 statistical/economic analysis, HTA report

Lay abstract: Septoplasty is surgery to straighten the part of the nose that divides the two nostrils (the septum). About 19000 septoplasty operations are carried out in the NHS each year. Ideally, the septum runs down the centre of the nose. If it is not straight, perhaps because of injury, it may narrow one side of the nose and obstruct airflow. On the sidewalls of the nose are “turbinates”, tissues which are full of blood vessels and glands. Often when the septum narrows one side of the nose, it creates a larger space on the other side, into which the turbinate on that side expands. When surgery to straighten the septum is carried out, some surgeons also reduce the turbinate tissue. Septoplasty is done in the hope of improving symptoms such as a blocked nose, snoring and sleep disturbance. Like any operation, there is a risk of complications. Most patients need to take at least 5 days off work or usual activities after the operation. Some patients seem not much better after the surgery. Practice varies around the country, and there is no good evidence about this operation or its alternatives, or about who might benefit most from treatment, to inform help patients and doctors decide when it should be carried out. NAIROS aims to provide this evidence by randomising patients to either septoplasty or non-surgical care (medical management). The medical management is a 6 months course of two nasal sprays – neither of which the patient is likely to have used before. Surgeons in the 16 NAIROS centres will continue to vary in their turbinate surgery, according to how they see individual patient needs. Operations involving any other procedure are excluded. Patients fill in symptom scores; Quality of life scores and have airflow measures carried out at the start, then at 6 and 12 months. We plan to look at the changes after surgery and medical treatment according to how bad their symptoms were in the first place, and if they are men or women. This will help us work out at the end of the study – who are the people who stand to gain most from a septoplasty operation. Patients we consulted told us they would prefer to be randomised to “deferred” rather than “never” surgery so patients will be seen at 6 months to measure the main outcome (22 item nasal symptom score) and give face to face feedback about how they are getting on, and so that we can measure nasal airflow again. Our health economic analysis looks at the NHS costs of nasal blockage and also looking at money spent by patients buying over the counter medicines, and time off work. We shall look at the frequency of complications. Because we know that randomising patients between surgical and non-surgical arms can be difficult, we will check in the first part of the trial that we are able to recruit patients (an internal pilot). Alongside the trial we will carry out interviews with patients and clinical staff. These interviews will help us understand a) why patients do or do not wish to take part in the trial b) patients’ experiences of septoplasty and the non-surgical arm c) how to put the findings of the trial into practice. The trial represents good value for money, since about £18 million of NHS money is spent on septoplasty operations each year, despite the fact that no one really know what the benefits are. Care Pathways in comparative or randomised trials Recruitment usually from dedicated research clinics. Patient information sheet sent with appointment to allow 'cooling off' hence recruit on Visit 1 if eligible and consenting. Patient information DVD will be shown prior to randomisation, unless patient has already accessed this on www.NAIROS.co.uk. Baseline measures - self report, demography and rhinospirometry recorded. Baseline recording will also be made of 3 core features - the side of the convexity; the site of deflection - whether anterior, posterior or both; whether the extent of the airway block by the septum is less than or greater than 50%. Brief NOSE questionnaire used at baseline to stratify patients into three severity categories against which outcome can ultimately be mapped. Once consented - random allocation to: Surgery – closed septoplasty, sutured, not packed, day case where possible, postoperative regime twice daily saline douche plus Naseptin cream (or, if patient peanut allergic, Bactroban ointment). Recommend 5 days off work – or 10 days if very dusty environment. Inferior turbinate submucosal tissue reduction to be carried out on the concave side, principally in the anterior portion of the turbinate where the nose is narrowest,according to clinician judgement of individual patient requirements. Intention to reduce turbinate will be recorded at recruitment. Surgery will be carried out within 6 to 8 weeks of randomisation by experienced (not trainee) surgeons to minimise incidence of technical failure OR Medical management - NAIROS participants in the medical management arm will be issued with a 6 months’ supply of ‘Sterimar’ saline nasal spray and mometasone 100mcg, each twice daily. Review - there are two review points at 6 and 12 months. Measures Objective - rhinospirometry, Subjective - SNOT-22 subscales; NOSE scale; Number and characteristics of any adverse events and surgical complication/ failure and re-intervention. Quality of life as measured by SF-36

Research activity codes: 6.4 SURGERY
Health categories: RESPIRATORY