Title: The STARFISH Trial: A randomised controlled trial of STeroid Administration Routes For Idiopathic Sudden sensorineural Hearing loss
Funder: Department of Health and Social Care

Abstract: Hearing loss is a common and disabling condition that may result from problems with the cochlea, the inner ear structure that senses sound and sends information to the brain. Loss of hearing due to damage to the cochlea can occur suddenly and without an obvious cause, a condition described as sudden sensorineural hearing loss (SSNHL). SSNHL can range from a mild hearing loss to a completely deaf ear, which can make it difficult to understand people talking on the affected side. Recovery of hearing following SSNHL may be helped by urgent treatment with steroids, but crucially we do not know if these work best given as tablets or by an injection through the ear drum. _x000D_ _x000D_ If SSNHL is identified more than a few weeks after it occurs, steroids may have little effect. A major problem is that patients with SSNHL may not be referred to Ear, Nose and Throat (ENT) surgeons in time to benefit from steroid treatment (within four weeks), due to delays in the hearing loss being recognised or referred by general practitioners (GPs). _x000D_ _x000D_ Sudden hearing loss is rare and we usually do not know why it happens. Steroids are the best treatment to try and improve the hearing, but we do not know whether it is best to give them by mouth or by an injection through the ear drum. We aim to find out by asking people with sudden hearing loss of unknown cause to be randomly chosen to have steroid treatment by mouth, injection into their ear, or both together. They will have a hearing test and fill in questionnaires before treatment and then six weeks and three months later to see how well their hearing recovers, as well as measure their dizziness and ringing in their ears._x000D_ _x000D_ One of the main problems with a trial like this is reaching patients with sudden hearing loss to encourage them to see their GP, and making sure their GPs refer them quickly to their local Ear Nose and Throat department for treatment. We will use a Facebook campaign to reach people with sudden hearing loss and encourage them to see their GP. We will use attaching sessions to remind GPs to refer straight away to their local hospital ENT department. As these patients are usually seen by junior ENT doctors, we will use a national group of junior ENT doctors to let patients know about the trial – this group have already been very successful if previous work at recruiting patients to research studies. _x000D_ _x000D_ We have worked with a group of patients who had sudden hearing loss to make sure that this research study is designed well and measures the issues that they felt were important. They thought that it would be a good idea to be able to test their hearing at home during the study as well as coming into the hospital for their hearing tests. We therefore included some hearing tests that can be performed on a smartphone, tablet or desktop computer at home for those patients who have one of these devices.._x000D_ _x000D_ The results of the research study will be shared with the public through our Facebook group, a website and newsletters as well as GPs, emergency doctors and ENT doctors through talks as meetings and changing guidelines for the treatment of sudden hearing loss.

Lay abstract: Background_x000D_ 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). _x000D_ _x000D_ Research question _x000D_ What is the best route of administration of steroid in ISSNHL: Oral, intratympanic or both combined?_x000D_ _x000D_ Objectives_x000D_ Primary objectives are:_x000D_ a) To establish and compare the effects of first-line oral, intratympanic, or oral and intratympanic steroids on functional hearing recovery in ISSNHL. _x000D_ b) To improve the early identification of ISSNHL in primary care._x000D_ Secondary objectives are:_x000D_ a) To complete a health economic assessment of different routes of steroid administration. _x000D_ b) To measure the trajectory to hearing recovery._x000D_ _x000D_ Methods_x000D_ 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._x000D_ Interventions: 525 participants will be randomised to one of the following interventions in a 1:1:1 ratio (175 per arm):_x000D_ 1) Oral steroid. Prednisolone 1mg/kg/day up to 60mg/day for 7 days (standard UK care)_x000D_ 2) Intratympanic steroid. dexamethasone 3.8mg/ml as 3 intratympanic injections (unless full recovery is reached), 7±2 days apart._x000D_ 3) Combined oral and intratympanic steroid using the above regimens._x000D_ 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._x000D_ _x000D_ 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._x000D_ 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:_x000D_ - Adverse events_x000D_ - Speech scores using Arthur Boothroyd word lists_x000D_ - Extent of hearing recovery (complete / partial / none) using an established classification_x000D_ - Dizziness (Vestibular Rehabilitation Benefit Questionnaire)_x000D_ - Tinnitus (Tinnitus Functional Index)_x000D_ - Time to hearing recovery measured in some participants via online hearing testing. _x000D_ _x000D_ Timelines for delivery_x000D_ 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._x000D_ _x000D_ Anticipated impact and dissemination_x000D_ 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.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: EAR