Research Protocol

Title
A prospective study comparing the efficacy of intratympanic steroid and systemic
steroid in the treatment of idiopathic sudden sensorineural hearing loss.

Objective1
To evaluate the efficacy of intratympanic steroid injection as an alternative to oral
steroid to improve hearing in cases of idiopathic sudden sensorineural hearing loss

Investigators
Principal investigator: Dr. FUNG Tai Hang Thomas
Co- investigator/ Supervisor: Dr. CHOW Shun Kit

Introduction
Although various methods of management have been used in the literature for sudden
sensorineural hearing loss (SSNHL), spontaneous recovery is high (32%-65%) within
the first 2 week of onset. This makes comparison of these treatment methods difficult.
Trental (Pentoxifylline intravenous or oral) and oral steroid have been the
conventional treatment in our unit. Intratympanic steroid had been used as salvage
treatment for SSNHL that is refractory to systemic steroid therapy. Multiple studies
have shown that intratympanic steroids are safe without causing cochlear dysfunction.
Due to the differences in the definition of improvement, response rate was variable.
Moreover, the effect of intratympanic steroid as an alternative to systemic steroid at
initial presentation has not been well studied.

Effect of Steroid on Cochlear

Intratympanic steroids have been shown to increase cochlear blood flow, prevent
aminoglycoside toxicity, prevent drill- induced noise loss and improve homeostasis
necessary cochlear function. Its efficacy is also attributed to the anti- inflammatory
and immunosuppressive effect to the inner ear. Steroids delivered intratympanically
can achieve high concentrations in perilymph, higher than when administered by

1
either intravenous or oral routes.

Advantages of Intratympanic steroid

The injection procedure can be office- based and is relatively easy to perform. High
concentration of steroid can be directed to the affected ear. Its can be used in cases
when systemic steroid is contraindicated e.g. TB, DM, HIV.

Potential Adverse effects of intratympanic steroid injection

Potential hazards of intratympanic steroid include pain, tympanic membrane
perforation, acute and chronic otitis media, vertigo, dysgeusia and potential worsening
of hearing.

Literature

Usefulness of systemic steroid

Wilson et al showed that patients with idiopathic SSNHL treated with systemic
steroid had statistically significant improvement than patients not receiving any
therapy (78% vs 38%). Moskowitz et al also had similar finding using similar finding
(89% vs 44%)

In an 8- year prospective study Byl FM et al, 45% of cases of SSNHL achieved

complete recovery regardless of any treatment.

Usefulness of intratympanic steroid in those who failed initial systemic steroid

therapy

In a randomized controlled trial involving 37 cases of SSNHL, Xenellis et al showed

that intratympanic steroid administration after failed intravenous steroids is safe and
effective treatment in SSNL. 47% of the trial group showed improvement by more
than 10dB pure tone average. No improvement was noted in those who did not
receive intratympanic steroid.
Summary of trials regarding the use of intratympanic steroid after failed systemic
steroid therapy

Author Percent improvement Criteria

Silverstein 1996 25% 10dB- PTA and 15% SDS

Parmes 1999 46% 5 normal threshold

Kopke 2001 83% 10dB PTA and 15% SDS

Gianoli 2001 44% 10dbPTA

Gouveris 2003 33% Within 10dB of normal ear

Ho 2004 53% 30db PTA

Slattery 2005 55% 10dB PTA

Xenellis 2006 47% 10dB PTA

Dallen 2006 75% 15dB PTA

Usefulness of intratympanic steroid as primary treatment

Banarjee and Parnes reported successful hearing improvement in 50% (mean PTA
improvement was 27db) when intratympanic methylprednisolone was used

In a case controlled study by Kakehata et al, 10 DM patients showed hearing

improvement in 70% (mean improvement was 41dB) vs historical group of 21
patients that received IV dexamethasone - 67%, mean improvement was 25dB PTA.

Materials and Methods

Our conventional therapy for idiopathic SSNHL is oral Prednisolone 30mg bd and
Oral Trental 400mg bd for 1 week. We planned to use substitute oral steroid with
intratympanic steroid injection as primary treatment for SSNHL. A prospective,
controlled trial will be performed. The trial group is consisted of approximately 25
cases of idiopathic SSNHL over a period of approximately 1 year. Cases in this group
will receive intratympanic steroid injection. Historical data (the most recent 25 cases
of idiopathic SSNHL treated in our unit) will be used as the control group, i.e. those
receiving oral Trental and steroid.

All cases will have a pure tone audiogram with the pure tone average of the thresholds
at 0.5,1,2,4 kHz calculated to determine the treatment hearing level prior treatment, 1
week, 2 weeks, 4 weeks and 3 months after treatment.

Steroid injection protocol

All trial cases will receive 4 intratympanic steroid injections over a course of 2 weeks.
Steroid used is methylprednisolone (Depomedro) 4%. Approximately 0.3- 0.4mL will
be injected using a 21G syringe to the anteroinferior quadrant of the tympanic
membrane of the affected ear until whitish fluid is seen behind the entire tympanic
membrane. Patient will be asked to rest with head titled towards the healthy side for
15minutes and avoid swallowing to allow the medication to distribute to the inner ear.
Side effects and subjective symptoms will be recorded

Inclusion Criteria
1. Idiopathic sudden sensorineural hearing loss of at least 30dB in 3 contiguous
frequencies over a period of 3 days or less.
2. Time period from onset of heating loss to treatment administration of 14 days
or less
3. No specific cause for the Sudden hearing loss after standard evaluation to
exclude identifiable causes
4. Pure tone average worse than 30dB
5. All age, sex, ethnicity will be included

Exclusion Criteria
1. History of ear disease
2. History of acoustic trauma
3. Previous otological surgery
4. History of previous exposure to ototoxic medication or radiotherapy to the
head and neck
5. History of previous adverse reaction to intratympanic steroid
Definition of Improvement
Improvement is defined as 30dB improvement in pure tone average of the affected ear
or restoration to normal hearing defined as threshold <20dB
Age, Sex, Shape of audiometry, presence of vertigo and tinnitus will also be recorded
The magnitude of improvement will also be compared between the trial and control
group.

Standard Evaluation to exclude identifiable causes:

ENT examination: external ear, tympanic membrane, nasopharynx, and cranial
nerves.
Basic Audiometry
Blood tests: CBC, ESR, LRFT, Syphilis serology, RF, autoimmune markers
MRI-IAM

Endpoint of Study
This study will end when the intended number of recruited cases has been followed
up with pure tone audiogram 3 months after the initial treatment.

References

Xenellis J et al. Intratympanic steroid treatment in idiopathic sensorineural hearing

loss: A controlled study Otolaryngol Head & Neck Surg 2006 Vol 134(6) p940-5

Guillermo P et al. Intratympanic steroids for treatment of sudden hearing loss after
failure of intravenous therapy. Otolaryngol Head & neck Surg. 2006 Vol137(1) p74-8

Marzo SJ. Intratympanic steroid perfusion for sudden sensorineural hearing loss.
Arch. Otolaryngology head & Neck Surg. 2005. Vol131(8) p730-2.

Haynes D S. et al. Intratympanic Dexamethasone for Sudden Sensorineural Hearing

Loss after Failure of Systemic Therapy. The Laryngoscope 2007 Vol 117(1) p 3–15.