Protocol for a multicentre randomised controlled trial of STeroid Administration Routes For Idiopathic Sudden sensorineural Hearing loss: The STARFISH trial

PLoS One. 2024 Feb 29;19(2):e0290480. doi: 10.1371/journal.pone.0290480. eCollection 2024.

Abstract

Idiopathic sudden sensorineural hearing loss (ISSNHL) is the rapid onset of reduced hearing due to loss of function of the inner ear or hearing nerve of unknown aetiology. Evidence supports improved hearing recovery with early steroid treatment, via oral, intravenous, intratympanic or a combination of routes. The STARFISH trial aims to identify the most clinically and cost-effective route of administration of steroids as first-line treatment for ISSNHL. STARFISH is a pragmatic, multicentre, assessor-blinded, three-arm intervention, superiority randomised controlled trial (1:1:1) with an internal pilot (ISRCTN10535105, IRAS 1004878). 525 participants with ISSNHL will be recruited from approximately 75 UK Ear, Nose and Throat units. STARFISH will recruit adults with sensorineural hearing loss averaging 30dBHL or greater across three contiguous frequencies (confirmed via pure tone audiogram), with onset over a ≤3-day period, within four weeks of randomisation. Participants will be randomised to 1) oral prednisolone 1mg/Kg/day up to 60mg/day for 7 days; 2) intratympanic dexamethasone: three intratympanic injections 3.3mg/ml or 3.8mg/ml spaced 7±2 days apart; or 3) combined oral and intratympanic steroids. The primary outcome will be absolute improvement in pure tone audiogram average at 12-weeks following randomisation (0.5, 1.0, 2.0 and 4.0kHz). Secondary outcomes at 6 and 12 weeks will include: Speech, Spatial and Qualities of hearing scale, high frequency pure tone average thresholds (4.0, 6.0 and 8.0kHz), Arthur Boothroyd speech test, Vestibular Rehabilitation Benefit Questionnaire, Tinnitus Functional Index, adverse events and optional weekly online speech and pure tone hearing tests. A health economic assessment will be performed, and presented in terms of incremental cost effectiveness ratios, and cost per quality-adjusted life-year. Primary analyses will be by intention-to-treat. Oral prednisolone will be the reference. For the primary outcome, the difference between group means and 97.5% confidence intervals at each time-point will be estimated via a repeated measures mixed-effects linear regression model.

Publication types

  • Clinical Trial Protocol

MeSH terms

  • Adult
  • Audiometry, Pure-Tone
  • Ear, Inner*
  • Hearing
  • Hearing Loss, Sensorineural* / drug therapy
  • Humans
  • Multicenter Studies as Topic
  • Prednisolone / therapeutic use
  • Randomized Controlled Trials as Topic

Substances

  • Prednisolone

Grants and funding

This work was funded by a grant from UK NIHR Health Technology Assessment, HTA Reference Number: NIHR131528. The grant was awarded to JRT and MES as joint lead applicants, with co-applicants CS, DV, DW, HJ, SM, RK, MB and TR: https://fundingawards.nihr.ac.uk/award/NIHR131528. The funder provided feedback on study design at an early stage, but has not had a role in protocol development or publication. The primary Sponsor for the study is the University of Birmingham, Edgbaston, Birmingham, B15 2TT. This research was supported by the NIHR Cambridge Biomedical Research Centre.