Efficacy and Safety of Intranasal Betahistine in the Treatment of Surgery-Induced Acute Vestibular Syndrome: A Double-Blind, Randomized, Placebo-Controlled Phase 2 Study.

OBJECTIVE

To evaluate the safety and efficacy of AM-125 nasal spray (intranasal betahistine) in the treatment of surgery-induced acute vestibular syndrome (AVS).

STUDY

DESIGN

Prospective, double-blind, randomized, placebo-controlled exploratory phase 2 study with dose escalation (part A) followed by parallel dose testing (part B); open-label oral treatment for reference.

SETTING

Twelve European study sites (tertiary referral centers).

PATIENTS: One hundred and twenty-four patients 18 to 70 years old undergoing surgery for vestibular schwannoma resection, labyrinthectomy or vestibular neurectomy with confirmed bilateral vestibular function presurgery and acute peripheral vertigo postsurgery.

INTERVENTIONS: AM-125 (1, 10, or 20 mg) or placebo or betahistine 16 mg p.o. t.i.d. for 4 weeks, starting 3 days postsurgery; standardized vestibular rehabilitation.

MAIN OUTCOME MEASURES: Tandem Romberg test (TRT) for primary efficacy, standing on foam, tandem gait, subjective visual vertical and spontaneous nystagmus for secondary efficacy, Vestibular Rehabilitation Benefit Questionnaire (VRBQ) for exploratory efficacy; nasal symptoms and adverse events for safety.

RESULTS

At treatment period end, mean TRT improvement was 10.9 seconds for the 20-mg group versus 7.4 seconds for the placebo group (mixed model repeated measures, 90% confidence interval = 0.2 to 6.7 s; p = 0.08). This was corroborated by nominally higher frequency of complete spontaneous nystagmus resolution (34.5% vs. 20.0% of patients) and improvement in the VRBQ; the other secondary endpoints showed no treatment effect. The study drug was well tolerated and safe.

CONCLUSIONS

Intranasal betahistine may help accelerate vestibular compensation and alleviate signs and symptoms of vestibular dysfunction in surgery-induced AVS. Further evaluation in a confirmatory manner appears warranted.