A randomized double-blind, placebo-controlled, cross-over trial (Vestparoxy) of the treatment of vestibular paroxysmia with oxcarbazepine

Journal of Neurology, Nov 2017

Objective Vestibular paroxysmia (VP) is characterized by short, often oligosymptomatic attacks of vertigo which occur spontaneously or are sometimes provoked by turning the head. Despite the description of the disease almost 40 years ago (first termed “disabling positional vertigo”), no controlled treatment trial has been published to date. The Vestparoxy trial was designed as a randomized, placebo-controlled, double-blind cross-over trial to examine the therapeutic effect of oxcarbazepine (OXA) in patients with definite or probable VP. Methods Patients were recruited from August 2005 to December 2011 in the outpatient Dizziness Unit of the Department of Neurology of the Munich University Hospital, and randomized to receive OXA (first week: 300 mg once per day, second week: 300 mg b.i.d., third week: 300 mg t.i.d. until the end of the third month), followed by placebo or vice versa with a 1-month wash-out period in between. The primary endpoint was the number of days with one or more attacks. Secondary endpoints were the number of attacks during the observed days, and the median (for each day) duration of attacks. All these endpoints were assessed using standardized diaries collected at the end of each treatment phase. Results Forty-three patients were randomized, 18 patients provided usable data (2525 patient days) for at least one treatment phase and were included in the main (intention-to-treat) analysis. The most common reasons for discontinuation documented were adverse events. The risk of experiencing a day with at least one attack was 0.41 under OXA, and 0.62 under placebo treatment, yielding a relative risk of 0.67 (95% CI 0.47–0.95, p = 0.025). The number of attacks during the observed days ratio was 0.53 (95% CI 0.42–0.68, p < 0.001) under OXA compared to placebo. Median attack duration was 4 s (Q25: 2 s, Q75: 120 s) under OXA, and 3 s (Q25: 2 s, Q75: 60 s) under placebo treatment. When days with no attacks, i.e., duration = 0, were included in the analysis, these figures changed to 0 (Q25: 0, Q75: 3 s), and 2 (Q25: 0, Q75: 6 s). No serious adverse events or new safety findings were identified during the trial. Conclusions The Vestparoxy trial showed a significant reduction of VP attacks under OXA compared to placebo treatment, confirming the known and revealing no new side effects.

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A randomized double-blind, placebo-controlled, cross-over trial (Vestparoxy) of the treatment of vestibular paroxysmia with oxcarbazepine

Journal of Neurology https://doi.org/10.1007/s00415 A randomized double‑blind, placebo‑controlled, cross‑over trial (Vestparoxy) of the treatment of vestibular paroxysmia with oxcarbazepine Otmar Bayer 0 1 Tatiana Brémová 0 1 Michael Strupp 0 1 Katharina Hüfner 0 1 Otmar Bayer 0 1 Michael Strupp 0 1 0 Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital of Psychiatry II, Medical University Innsbruck , Innsbruck , Austria 1 Department of Neurology, Munich University Hospital , Munich , Germany 2 Tatiana Brémová Objective Vestibular paroxysmia (VP) is characterized by short, often oligosymptomatic attacks of vertigo which occur spontaneously or are sometimes provoked by turning the head. Despite the description of the disease almost 40 years ago (first termed “disabling positional vertigo”), no controlled treatment trial has been published to date. The Vestparoxy trial was designed as a randomized, placebo-controlled, double-blind cross-over trial to examine the therapeutic effect of oxcarbazepine (OXA) in patients with definite or probable VP. Methods Patients were recruited from August 2005 to December 2011 in the outpatient Dizziness Unit of the Department of Neurology of the Munich University Hospital, and randomized to receive OXA (first week: 300 mg once per day, second week: 300 mg b.i.d., third week: 300 mg t.i.d. until the end of the third month), followed by placebo or vice versa with a 1-month wash-out period in between. The primary endpoint was the number of days with one or more attacks. Secondary endpoints were the number of attacks during the observed days, and the median (for each day) duration of attacks. All these endpoints were assessed using standardized diaries collected at the end of each treatment phase. Results Forty-three patients were randomized, 18 patients provided usable data (2525 patient days) for at least one treatment phase and were included in the main (intention-to-treat) analysis. The most common reasons for discontinuation documented were adverse events. The risk of experiencing a day with at least one attack was 0.41 under OXA, and 0.62 under placebo treatment, yielding a relative risk of 0.67 (95% CI 0.47-0.95, p = 0.025). The number of attacks during the observed days ratio was 0.53 (95% CI 0.42-0.68, p < 0.001) under OXA compared to placebo. Median attack duration was 4 s (Q25: 2 s, Q75: 120 s) under OXA, and 3 s (Q25: 2 s, Q75: 60 s) under placebo treatment. When days with no attacks, i.e., duration = 0, were included in the analysis, these figures changed to 0 (Q25: 0, Q75: 3 s), and 2 (Q25: 0, Q75: 6 s). No serious adverse events or new safety findings were identified during the trial. Conclusions The Vestparoxy trial showed a significant reduction of VP attacks under OXA compared to placebo treatment, confirming the known and revealing no new side effects. Vertigo; Randomized controlled trial; Cross-over studies; Class II Level of evidence; Vestibular paroxysmia; Neuro-vascular cross compression; Oxcarbazepine - Otmar Bayer, Tatiana Brémová and Katharina Hüfner have contributed equally to the research. Abbreviations AEs Adverse events AICA Anterior inferior cerebellar artery 1 German Center for Vertigo and Balance Disorders, Campus Großhadern, Munich University Hospital, Marchioninistrasse 15, 81377 Munich, Germany ATD Vestibular paroxysmia (VP) is characterized by recurrent, brief, mono- or oligosymptomatic attacks of vertigo which occur spontaneously or are rarely triggered by a provoking factor, most commonly a head or body turn [ 1, 2 ]. The condition was first described in 1975 along the lines of trigeminal neuralgia and hemifacial spasm, and was termed “disabling positional vertigo” [ 3, 4 ]. The initial nomenclature reflects the fact that affected patients are often severely disabled and cannot work or participate in daily activities. Since then some case reports and case series on the condition have been published, e.g., [ 5, 6 ], but no randomized controlled trials have been carried out. The clinical diagnostic criteria of VP were first provided by Brandt and Dieterich [ 6 ] and then refined by Hüfner [ 1 ]. Although the disease is recognized as a diagnosis in most major dizziness centers (see [ 1, 7 ] for details) the absence of a gold standard diagnostic test has evidently hindered treatment studies on the topic. Most available clinical studies focus on the ancillary investigations, namely imaging data [ 1, 8 ]. It is now widely accepted that neuro-vascular cross compression (NVCC) of the eighth nerve leading to demyelination with ephaptic depolarization is the most probable underlying pathomechanism [ 9 ], although the finding of asymptomatic NVCC has been reported [ 10 ]. NVCC of the eighth nerve could be detected in all VP patients, resulting in a sensitivity of 100% and a specificity of 65% for the diagnosis of VP by MRI [ 8 ]. The vessels are mainly arteries, most often the anterior inferior (...truncated)


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Otmar Bayer, Tatiana Brémová, Michael Strupp, Katharina Hüfner. A randomized double-blind, placebo-controlled, cross-over trial (Vestparoxy) of the treatment of vestibular paroxysmia with oxcarbazepine, Journal of Neurology, 2017, pp. 1-8, DOI: 10.1007/s00415-017-8682-x