A research study to find out whether steroids given by mouth, an injection through the ear drum, or a combination of both treatments is best at improving hearing after unexplained sudden hearing loss.
| ISRCTN | ISRCTN10535105 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN10535105 |
| EudraCT/CTIS number | 2022-000085-17 |
| IRAS number | 1004878 |
| Secondary identifying numbers | RG_21-145, IRAS 1004878, CPMS 53517 |
- Submission date
- 02/07/2022
- Registration date
- 02/12/2022
- Last edited
- 08/10/2024
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Ear, Nose and Throat
Plain English Summary
Background and study aims
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. 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). Sudden hearing loss is rare and we usually do not know why it happens. Steroids are the best treatment to try and improve hearing, but we do not know whether it is best to give them by mouth or by an injection through the ear drum.
Who can participate?
Adults aged 18 years or over with ISSNHL in the last 4 weeks.
What does the study involve?
People with sudden hearing loss of unknown cause will 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. 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 teaching 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.
What are the possible benefits and risks of participating?
Benefits:
This group have already been very successful if previous work at recruiting patients to research studies. 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. 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 at meetings and changing guidelines for the treatment of sudden hearing loss.
Risks:
Interventions:
- Both oral and injected steroid are commonly used treatments for ISSNHL in the UK with a good safety profile.
- Short-course high dose oral steroids have few risks if given according to the protocol. The most common side effects are altered mood or poor sleep, and these resolve when treatment finishes.
- Exclusion criteria ensure that patients at greater risk of side effects (e.g. pregnant women) are excluded.
- Intratympanic injection also has an established safety profile. It may be briefly uncomfortable, cause vertigo and occasionally infection and patients will be warned of these risks during the consent process and in specific patient information sheets for each treatment arm.
- Very rarely transtympanic injection could cause further permanent hearing loss, usually technique-related. Investigators performing injection will be required to review training material (written and video) and trainees/surgeons new to the technique will be supervised.
- Written instructions will be provided to participants regarding their allocated treatment, including information on side effects and who to contact in the event of a problem.
- GPs will be informed of the allocated treatment.
Research procedures:
- Additional research procedures include in-hospital speech hearing tests, questionnaires, and for some patients home hearing assessment.
- The main burden on participants is that slightly longer appointments will be required than those of standard of care. Follow up has been reduced to the minimum possible, and designed to coincide with standard care appointments.
- Although the questionnaires do not address sensitive issues, participants may find completing the questionnaires slightly distressing, or a burden on time. This risk will be explained during consent.
- Participants will be encouraged to perform online hearing tests weekly. Given potential time burdens or difficulty with internet access, these are optional. The tests are provided by an established developer of online hearing assessment tools and are designed to be simple to use with personal electronic devices and headphones.
Comprehension:
- Trial information will be made available in video and written format to maximise accessibility. The information sheet has been reviewed by patients to ensure accessibility.
Confidentiality:
- The trial is designed in accordance with the Birmingham Clinical Trials Unit (BCTU) Standard Operating Procedures.
- Site researchers will follow local NHS Trust policy on Data Protection.
- In correspondence, identifiers will be limited to Trial ID ± partial date of birth.
- Home hearing testing data will be associated with a code separate to the trial ID to ensure effective pseudo-anonymisation.
Where is the study run from?
University of Birmingham (UK)
When is the study starting and how long is it expected to run for?
June 2022 to May 2027
Who is funding the study?
National Institute for Health and Care Research (NIHR) (UK)
Who is the main contact?
starfish@trials.bham.ac.uk
Contact information
Public
University of Birmingham
Birmingham
B15 2TT
United Kingdom
| starfish@trials.bham.ac.uk |
Principal Investigator
Hills Road
Cambridge
CB2 0QQ
United Kingdom
 ORCID ID |
0000-0002-2483-8700 |
|---|---|
| Phone | +44 1223 256051 |
| jrt20@cam.ac.uk |
Principal Investigator
Hills Road`
Cambridge
CB2 0QQ
United Kingdom
| ORCID ID |
0000-0001-8147-1549 |
|---|---|
| mes39@cam.ac.uk |
Scientific
University of Birmingham
Birmingham
B15 2TT
United Kingdom
| ORCID ID |
0000-0001-7096-513X |
|---|---|
| S.MEHTA.1@bham.ac.uk |
Study information
| Study design | Interventional single-blind randomized parallel-group controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | 42015 STARFISH PIS v2.0 07Oct2022.pdf |
| Scientific title | A randomised controlled trial of STeroid Administration Routes For Idiopathic Sudden sensorineural Hearing loss: The STARFISH Trial |
| Study acronym | STARFISH |
| Study hypothesis | Primary objective: To establish the relative effects of oral, intratympanic, or combined oral and intratympanic steroids on hearing recovery in ISSNHL, when used as first line management. Other objectives: Hearing outcome To use participant submitted data to explore the rate of hearing recovery. Economic Aims and Objectives To establish the cost-effectiveness of oral, intratympanic or combined oral and intratympanic steroids as the first line of treatment for ISSNHL. Exploratory Objectives To improve the early identification and onward referral of ISSNHL in primary care. |
| Ethics approval(s) | Approved 07/11/2022, London - Harrow Research Ethics Committee (Level 3, Block B, Whitefriars, Lewins Mead, Bristol, BS1 2NT, UK; +44 207 104 8246; harrow.rec@hra.nhs.uk), ref: 22/LO/0532 |
| Condition | Idiopathic sudden sensorineural hearing loss |
| Intervention | Oral steroid (Prednisolone) 1mg/Kg/day up to 60mg/day for 7 days or Intratympanic steroid (Dexamethasone) three intratympanic injections 3.3mg/ml or 3.8mg/ml spaced 7±2 days apart or Combined oral (Prednisolone) and intratympanic (Dexamethasone) steroid as described above, with the first intratympanic injection occurring within four days of starting oral steroids |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Prednisolone, dexamethasone |
| Primary outcome measure | The absolute improvement in pure tone audiogram average (calculated at 0.5, 1.0, 2.0, 4.0 kHz) at 12 weeks after randomisation |
| Secondary outcome measures | At 6 and 12 weeks post randomisation: 1. Functional hearing 1.1. Hearing related to speech: using The Speech, Spatial and Qualities of hearing scale (SSQ). SSQ is a validated measure, in the form of a short questionnaire, known to provide a good representation of the functional relationship with speech in everyday life and has been used to assess the disability of unilateral hearing loss seen in ISSNHL, providing disability scores associated with different aspects of hearing. 1.2. The absolute improvement in pure tone audiogram average (calculated at 0.5, 1.0, 2.0, 4.0 kHz). 1.3. Actual hearing thresholds measured by pure tone audiogram average following treatment initiation (calculated at 0.5, 1.0, 2.0, 4.0 kHz). 1.4. High frequency hearing threshold measured by the absolute improvement in pure tone audiogram average across 4.0, 6.0 and 8.0 kHz. 1.5. Recovery of speech perception: using Arthur Boothroyd (AB) word lists scored by phoneme. 1.6. Extent of hearing recovery: using an established classification of recovery (complete/partial/none) based on pure tone audiogram and speech perception 1.7. Time to hearing recovery: using online digits-in-noise and pure tone tests (Optional and recommended weekly where done). 2. Associated Symptoms 2.1. Dizziness: using the Vestibular Rehabilitation Benefit Questionnaire (VRBQ). 2.2. Tinnitus: using the Tinnitus Functional Index (TFI). 3. Adverse Events (AEs) 3.1. Adverse events relevant to the interventions 4. Health Economic Assessment 4.1. Two tools will be used to assess health economics: the Health Utilities Index 3 (HUI3), a participant reported assessment of health-related quality of life suited to hearing loss, and ICEpop CAPability measure for Adults (ICECAP-A), a participant reported measure of capability for the adult population 4.2. Resource usage |
| Overall study start date | 01/12/2021 |
| Overall study end date | 31/05/2027 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 525 |
| Participant inclusion criteria | 1. Adults aged 18 years or over 2. Diagnosis of new-onset ISSNHL- sensorineural hearing loss of 30 decibels (dBHL) or greater occurring within a 3-day period and including 3 contiguous pure-tone frequencies (out of 0.5, 1.0, 2.0, 4.0 kilohertz (kHz)) confirmed with a pure tone audiogram occurring within a 3-day period (based on participant reported history) 3. Onset of hearing loss within 4 weeks prior to randomisation 4. English spoken as a first or second language |
| Participant exclusion criteria | 1. Identified cause for hearing loss (not idiopathic) 2. Bilateral ISSNHL 3. Received prior steroid treatment for the same episode of ISSNHL 4. Medical contraindication to high dose systemic steroids 5. Previous history of psychosis 6. On oral steroid therapy for another condition 7. Known adrenocortical insufficiency other than exogenous corticosteroid therapy 8. Hypersensitivity to the active substance or to any of the excipients 9. Has a systemic infection unless specific anti-infective therapy is employed 10. Has ocular herpes simplex 11. Has ipsilateral acute or chronic active middle ear disease (including acute otitis media, chronic suppurative otitis media and cholesteatoma, excluding dry perforation) 12. Does not have the capacity to provide written informed consent |
| Recruitment start date | 01/02/2023 |
| Recruitment end date | 30/11/2026 |
Locations
Countries of recruitment
- England
- Northern Ireland
- Scotland
- United Kingdom
- Wales
Study participating centres
Aberdeen
AB25 2ZN
United Kingdom
Hills Road
Cambridge
CB2 0QQ
United Kingdom
Broomfield
Chelmsford
CM1 7ET
United Kingdom
London
W6 8RF
United Kingdom
Charter Way
Turner Road
Colchester
CO4 5JL
United Kingdom
Liverpool Road
Chester
CH2 1UL
United Kingdom
High Heaton
Newcastle upon Tyne
NE7 7DN
United Kingdom
Dalton Lane
Barrow-in-furness
LA14 4LF
United Kingdom
Carmarthen
SA31 2AF
United Kingdom
Glasgow
G4 0SF
United Kingdom
Gloucester
GL1 3NN
United Kingdom
Marlborough Road
Swindon
SN3 6BB
United Kingdom
Huntingdon
PE29 6NT
United Kingdom
Middlesbrough
TS4 3BW
United Kingdom
Gorleston
Great Yarmouth
NR31 6LA
United Kingdom
Headington
Oxford
OX3 9DU
United Kingdom
Rothwell Road
Kettering
NN16 8UZ
United Kingdom
Kingston upon Thames
KT2 7QB
United Kingdom
Leicester
LE1 5WW
United Kingdom
Leeds
LS1 3EX
United Kingdom
Lincoln
LN2 5QY
United Kingdom
Stevenage
SG1 4AB
United Kingdom
Prescot Street
Liverpool
L7 8XP
United Kingdom
Oxford Road
Manchester
M13 9WL
United Kingdom
Cwmrhydyceirw
Swansea
SA6 6NL
United Kingdom
Taunton
TA1 5DA
United Kingdom
Dundee
DD1 9SY
United Kingdom
Watford Road
Harrow
HA1 3UJ
United Kingdom
Bretton Gate
Bretton
Peterborough
PE3 9GZ
United Kingdom
Longfleet Road
Poole
BH15 2JB
United Kingdom
Grainger Drive
Apley
Telford
TF1 6TF
United Kingdom
Edgbaston
Birmingham
B15 2TH
United Kingdom
Cosham
Portsmouth
PO6 3LY
United Kingdom
Glasgow
G51 4TF
United Kingdom
Burton-on-trent
DE13 0RB
United Kingdom
Derby Road
Nottingham
NG7 2UH
United Kingdom
London Road
Reading
RG1 5AN
United Kingdom
Blackburn
BB2 3HH
United Kingdom
Farnworth
Bolton
BL4 0JR
United Kingdom
Derby
DE22 3NE
United Kingdom
Barrack Road
Exeter
EX2 5DW
United Kingdom
Pond Street
London
NW3 2QG
United Kingdom
Sheffield
S10 2JF
United Kingdom
Lancaster
LA1 4RP
United Kingdom
Stoke-on-trent
ST4 6QG
United Kingdom
Bath
BA1 3NG
United Kingdom
Belfast
BT12 6BA
United Kingdom
Eccles
Salford
M6 8HD
United Kingdom
West Bromwich
B71 4HJ
United Kingdom
Prittlewell Chase
Westcliff-on-sea
SS0 0RY
United Kingdom
Livingston
EH54 6PP
United Kingdom
Hazel Grove
Stockport
SK2 7JE
United Kingdom
Ashton-under-lyne
OL6 9RW
United Kingdom
Wigan
WN1 1RU
United Kingdom
Torquay
TQ2 7AA
United Kingdom
London
NW1 2PG
United Kingdom
Walsgrave
Coventry
CV2 2DX
United Kingdom
Airdrie
ML6 0JS
United Kingdom
Cardiff
CF14 4XW
United Kingdom
Wexham
Slough
SL2 4HL
United Kingdom
Wrexham Technology Park
Wrexham
LL13 7TD
United Kingdom
Wythenshawe
Manchester
M23 9LT
United Kingdom
Penrhosgarnedd
Bangor
LL57 2PW
United Kingdom
Sponsor information
University/education
Aston Webb Building, Room 117n
Edgbaston
Birmingham
B15 2TT
England
United Kingdom
| Phone | +44 121 4058011 |
|---|---|
| researchgovernance@contacts.bham.ac.uk | |
| Website | http://www.birmingham.ac.uk/index.aspx |
"ROR" |
https://ror.org/03angcq70 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/07/2027 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Peer reviewed scientific journals Internal report Conference presentation Publication on website Other Data sharing of individual patient data will be via submission of a request to the Trial Management Group. |
| IPD sharing plan | The final dataset will be available to members of the TMG and co-applicant group who need access to the data to undertake the final analyses. Any request for data generated in this trial will be considered by BCTU. Data will typically be available 6 months after the primary publication unless it is not possible to share the data (for example: the trial results are to be used as part of a regulatory submission, the release of the data is subject to the approval of a third party who withholds their consent, or BCTU is not the controller of the data). Only scientifically sound proposals from appropriately qualified Research Groups will be considered for data sharing. The request will be reviewed by BCTU Data Sharing Committee in discussion with the CI and deputy CI and, where appropriate (or in the absence of the CI and deputy CI) any of the following: the trial sponsor, TMG and independent TSC. A formal Data Sharing Agreement (DSA) may be required between respective organisations once release of the data is approved and before data can be released. The data will be fully de-identified (anonymised) unless the DSA covers transfer of participant identifiable information. Any data transfer will use a secure and encrypted method. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | version 2.0 | 07/10/2022 | 15/11/2022 | No | Yes |
| Protocol file | version 3.0 | 10/10/2022 | 15/11/2022 | No | No |
| Study website | 15/11/2022 | No | No | ||
| Study website | INTEGRATE link | 15/11/2022 | No | No | |
| Protocol (other) | 01/12/2022 | No | No | ||
| HRA research summary | 26/07/2023 | No | No | ||
| Protocol article | 29/02/2024 | 01/03/2024 | Yes | No |
Additional files
Editorial Notes
08/10/2024: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/10/2024 to 30/11/2026.
2. The overall end date was changed from 30/04/2025 to 31/05/2027.
3. The intention to publish date was changed from 30/04/2026 to 31/07/2027.
4. The plain English summary was updated to reflect these changes.
01/03/2024: Publication reference added.
15/03/2023: The recruitment start date has been changed from 01/01/2023 to 01/02/2023.
16/01/2023: Internal review.
04/07/2022: Trial's existence confirmed by NHS HRA.
