The STARFISH Trial: A randomised controlled trial of STeroid Administration Routes For Idiopathic Sudden sensorineural Hearing loss

Background Sudden sensorineural hearing loss (SSNHL) is the rapid onset of reduced hearing due to loss of function of the inner ear or hearing nerve. Often the cause is unknown, a condition known as idiopathic sudden sensorineural hearing loss (ISSNHL). ISSNHL is usually unilateral and can result in permanent and complete hearing loss, profoundly impacting a patient’s quality of life. Evidence supports improved hearing recovery with early steroid treatment, via oral, intravenous or intratympanic routes(1, 2). Identification of the most clinically and cost-effective route of administration of steroids as first-line treatment for ISSNHL is a high-priority research recommendation from NICE(3). Research question What is the best route of administration of steroid in ISSNHL: Oral, intratympanic or both combined? Objectives Primary objectives are: a) To establish and compare the effects of first-line oral, intratympanic, or oral and intratympanic steroids on functional hearing recovery in ISSNHL. b) To improve the early identification of ISSNHL in primary care. Secondary objectives are: a) To complete a health economic assessment of different routes of steroid administration. b) To measure the trajectory to hearing recovery. Methods Study population: Adults with new-onset ISSNHL, defined as sensorineural hearing loss of >30 dBHL over 3 contiguous pure-tone frequencies occurring within a 3-day period. Interventions: 525 participants will be randomised to one of the following interventions in a 1:1:1 ratio (175 per arm): 1) Oral steroid. Prednisolone 1mg/kg/day up to 60mg/day for 7 days (standard UK care) 2) Intratympanic steroid. dexamethasone 3.8mg/ml as 3 intratympanic injections (unless full recovery is reached), 7±2 days apart. 3) Combined oral and intratympanic steroid using the above regimens. 75 UK sites will be recruited working with INTEGRATE the UK ENT Trainee Research Network. Recruitment will be optimised through GP training and working with a national GP research network to enhance referral of cases, and social media to target patients. Primary outcome: Absolute improvement in pure tone audiogram average at 3 months following treatment initiation (calculated at 0.5, 1.0, 2.0, 4.0 kHz) (2), assessed by an audiologist blinded to the treatment. Secondary outcomes measuring the functional recovery of hearing and other effects on daily life will be assessed at 6 and 12 weeks. The Speech, Spatial, and Qualities of Hearing Scale will be used to provide disability scores associated with different aspects of hearing loss. This is a key measure of functional impact, particularly with asymmetric hearing loss(4,5). We will also measure: - Adverse events - Speech scores using Arthur Boothroyd word lists - Extent of hearing recovery (complete / partial / none) using an established classification - Dizziness (Vestibular Rehabilitation Benefit Questionnaire) - Tinnitus (Tinnitus Functional Index) - Time to hearing recovery measured in some participants via online hearing testing. Timelines for delivery Commencing December 2021, total study duration will be 41 months(m): 6m set up, 9m internal pilot, 16m further recruitment, 3m follow up and 7m analysis and dissemination. Anticipated impact and dissemination Update to UK clinical guidance on the management of ISSNHL, increased patient awareness via social media and charities, and awareness of professionals via Ear Nose and Throat, Audiology and GP journals and conferences.