title: Intratympanic gentamicin treatment for Ménière's disease: a randomized, double-blind, placebo-controlled trial on dose efficacy - results of a prematurely ended study.
abstract: BACKGROUND
  Gentamicin 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.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  During 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.
  
  
  CONCLUSIONS
  No 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.
  
  
  BACKGROUND
  This trial was registered in The University Medical Center Utrecht/ Gelre hospital Apeldoorn. Protocol ID: 07/343, EudraCT number 2006-005913-37.
authors.affiliation: Department of Otorhinolaryngology, University Medical Center Utrecht, Heidelberglaan 100, Room G,02,531, Utrecht 3584 CX, The Netherlands. ent-research@umcutrecht.nl.
authors.forename: Hendrik G
authors.initials: HG
authors.lastname: Bremer
authors.forename: Ingrid
authors.initials: I
authors.lastname: van Rooy
authors.forename: Bas
authors.initials: B
authors.lastname: Pullens
authors.forename: Carla
authors.initials: C
authors.lastname: Colijn
authors.forename: Inge
authors.initials: I
authors.lastname: Stegeman
authors.forename: Hester J
authors.initials: HJ
authors.lastname: van der Zaag-Loonen
authors.forename: Peter Paul
authors.initials: PP
authors.lastname: van Benthem
authors.forename: Sjaak F L
authors.initials: SF
authors.lastname: Klis
authors.forename: Wilko
authors.initials: W
authors.lastname: Grolman
authors.forename: Tjasse D
authors.initials: TD
authors.lastname: Bruintjes
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D001301:Audiometry, Pure-Tone; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004432:Ear, Middle; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage* / Q000009:adverse effects; D034381:Hearing Loss / Q000139:chemically induced; D006801:Humans; D008297:Male; D008575:Meniere Disease / Q000188:drug therapy*; D008875:Middle Aged; D010919:Placebos
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins; D010919:Placebos