The Effecttiveness of Intratympanic Methylprednisolon Injections Compared to Placebo in the Treatment of Vertigo Attacks in Meniere's Disease

Официальное название

A Multicenter, Double-blinded, Randomized, Placebo-controlled Trial to Compare the Effectiveness of Intratympanic Injections methylPREDnisolon Versus Placebo in the Treatment of Vertigo Attacks in MENière's Disease (PREDMEN Trial).

Обзор

Ménière's disease is an inner ear disorder in which patients suffer from attacks of vertigo, tinnitus and hearing loss. To date, it is unclear what the best treatment for this condition is. Giving injections in the inner ear with the adrenal cortical hormone methylprednisolone is a treatment that is already widely used, but still there is insufficient evidence in the effectiveness of this treatment. This multicenter trial compares a patient group which receives injections of methylprednisolone to a patient group which receives placebo injections. Subsequently, dizziness, tinnitus, hearing loss and quality of life will be assed and compared for the above mentioned groups, over a period of one year.

Подробное описание

Meniere's disease is an inner ear disease characterized by recurrent episodes of vertigo, hearing loss, tinnitus and aural fullness. It is estimated that 15000 patients in de Netherlands suffer from this disease. Endolymfactic hydrops is thought to be the underlying pathophysiology of the symptoms. Salt restriction, oral medication (diuretics and betahistine), intratympanic gentamicin and steroids, ablative surgery, and endolymphatic sac surgery are some of the current therapy options. A probable effectiveness of the treatment with intratympanic gentamicin is found but this treatment is ototoxic and carries a risk of hearing loss. Methylprednisolone injections have been shown to be safer, however there is insufficient data to support the efficacy of this treatment. Therefore in this double-blinded, randomized, placebo-controlled trial, effectiveness of intratympanic injections with methylPREDnisolon versus placebo in the treatment of vertigo attacks in MENière's disease is compared.

The investigators aim to include 74 patients in each arm, based on a statistical power of 80 percent. Patients will be randomly randomized to one of the two treatment arms, receiving either a placebo injection or a methylprednisolone sodium succinate injection at a dose of 62.5 mg/ml. After 14 days, this injection will be given once more. A follow-up visit will be scheduled after six and twelve months and telephone follow-up calls will be scheduled after three and nine months. The primary objective will be the control of vertigo, with secondary outcomes including hearing loss, tinnitus, the frequency of escape interventions, quality of life, adverse events and cost effectiveness.

Вмешательства

• Препарат Methylprednisolon
  Intratympanal injection with Methylprednisolon 62.5 mg/ ml
• Препарат Placebo
  Intratympanal injection with saline, natriumchloride 0.9%

Первичные конечные точки

• Vertigo spells [Срок оценки: Daily, change from baseline to one year]

Вторичные конечные точки (11)

• Hearing loss [Срок оценки: At baseline, 6 months and 12 months]
• Tinnitus [Срок оценки: At baseline, 6 months and 12 months]
• health-related quality of life [Срок оценки: At baseline, 6 months and 12 months]
• health-related quality of life [Срок оценки: At baseline, 6 months and 12 months]
• Escape medication [Срок оценки: At baseline, 3 months, 6 months, 9 months, 12 months]
• Adverse events [Срок оценки: Daily, change from baseline to one year]
• Cost-effectiveness [Срок оценки: At baseline, 6 months and 12 months]
• Co-interventions [Срок оценки: Daily, change from baseline to one year]
• Overall function [Срок оценки: At baseline, 6 months and 12 months]
• Impact of Dizziness [Срок оценки: Change from baseline to 6 months to 12 months]
• Tinnitus severity [Срок оценки: At baseline, 6 months and 12 months]

Критерии участия

Критерии включения

• Unilateral, definite MD according to the diagnostic criteria derived from the American Academy Otolaryngology Head and Neck Surgery, Classification Committee of the Bárány Society, European Academy of Otology and Neurotology and International Classification of Vestibular Disorders published in 2015 \[7\] (see Appendix 1):

Definite MD Two or more spontaneous episodes of vertigo, each lasting 20 minutes to 12 hours, AND Audiometrically documented low- to medium-frequency sensorineural hearing loss in one ear, defining the affected ear on at least one occasion before, during or after one of the episodes of vertigo, AND Fluctuating aural symptoms (hearing, tinnitus, or fullness) in affected ear (not better accounted for by another vestibular diagnosis)

• age > 18 years at the start of the trial.
• ≥ 4 vertigo attacks over the last 6 months.
• willing to adhere to daily trial medications and the follow-up assessments.

Критерии исключения

A potential subject who meets any of the following criteria will be excluded:

• bilateral MD
• severe disability (e.g. neurological, orthopaedic, cardiovascular) or serious concurrent illness that might interfere with treatment or follow-up.
• active additional neuro-otologic disorders that may mimic MD (e.g. vestibular migraine, recurrent vestibulopathy, phobic postural vertigo, vertebro-basilar TIAs, acoustic neuroma).
• otitis media with effusion based on tympanogram results.
• history of intratympanic injections with corticosteroid less than 6 months ago.
• history of intratympanic injections with gentamicin or ear surgery for treating MD.
• pregnant women and nursing women.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Нидерланды · 1 центр

• Leiden University Medical Centre — Leiden

Публикации

• Boreel MME, van Esch B, Schermer TR, Mol BM, van Benthem PP, Bruintjes TD. The effectiveness of intratympanic injections with methylPREDnisolon versus placebo in the treatment of vertigo attacks in MENiere's disease (PREDMEN trial): a study protocol for a phase-3 multicentre, double-blinded, randomised, placebo-controlled trial. BMJ Open. 2024 Aug 29;14(8):e076872. doi: 10.1136/bmjopen-2023-076872 PMID 39209781

Идентификаторы

NCT: NCT05851508 · PREDMEN · 10140022110009

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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