Intratympanic gentamicin treatment for Ménière’s disease: a randomized, double-blind, placebo-controlled trial on dose efficacy - results of a prematurely ended study

Abstract

BackgroundGentamicin is used as a therapeutic agent for Ménière’s disease because of its vestibulotoxicity causing chemo-ablation of the vestibular sensory epithelia. Its use has increased in recent years. However, there is still no consensus about the dose regimen of gentamicin in the treatment of Ménière’s disease. In this study two different dose regimen treatment protocols are compared in a placebo controlled study design. The primary objective is to quantify the treatment effect on dizziness, the secondary objective is hearing evaluation.MethodsWe performed a randomized, double-blind, placebo-controlled study in adults with unilateral Ménière’s disease according to the AAO-HNS guidelines resistant to conservative medication. Three groups received four injections, administered weekly (four intratympanic injections with 40 mg/mL gentamicin solution, two injections gentamicin solution and two injections of placebo in random order, or four injections with placebo). Outcome measures were the score on the Dizziness Handicap Inventory and pure tone audiometry (PTA). Intended follow-up was 2 years.ResultsDuring follow-up one patient exceeded the accepted amount of hearing loss. Further, enrollment was very slow (until 12 months between two patients) and new insights showed an apparent benefit of intratympanic gentamicin treatment (ITG). Therefore we performed an unscheduled interim analysis which showed that PTA threshold shifts reached the stopping criteria in two more patients. Because of this, this study was ended. Of the three patients with the significant PTA threshold shift two were enrolled in the gentamicin group.ConclusionNo conclusions can be drawn concerning doses regimens. Now that new publications have shown that ITG treatment can be an effective and safe treatment, a placebo-controlled randomized controlled trial may not pass the ethical committee because of these recent reports in literature. Still, a dose regimen study (without placebo) on ITG treatment needs to be performed.Trial registrationThis trial was registered in The University Medical Center Utrecht/ Gelre hospital Apeldoorn. Protocol ID: 07/343, EudraCT number 2006-005913-37.

Sustained and Transient Vestibular Systems: A Physiological Basis for Interpreting Vestibular Function

“…VOR gain measured in this way is a global measure of the whole response to a head turn, and as such, it cannot show the fine detail of the time series of the response which may reflect the way in which the sustained and transient systems are combined. Fortuitously, an answer about how these systems work may be provided by the therapeutic treatment of patients with Meniere’s disease by the use of intratympanic injections of gentamicin (ITG) (107–111). …”

Intratympanic therapy in Meniere's syndrome or disease: up to date evidence for clinical practice

“…Although Bremer et al . was excluded from our analysis, it is worth noting that even in a small sample size they highlighted hearing loss in three patients in the gentamicin group.…”

“…We excluded Bremer et al 10 from our analysis. The RCT was terminated prematurely and the authors acknowledge that their sample size was too small to draw any meaningful conclusions [n = 5, 4 and 5 in each arm].…”

Inner ear delivery: Challenges and opportunities

“…Intratympanic injection, which involves filling the middle ear with a drug and relying on diffusion into the inner ear, can attain higher inner ear drug concentrations . However, intratympanic injection suffers from unintentional clearance of the drug via the eustachian tube, inconsistent diffusion rate into the inner ear, and risk of damaging middle ear structures . Direct microinjection of drugs through a cochleostomy is an alternative method that reduces the variability associated with intratympanic injection but carries the risk of significant trauma to the inner ear .…”