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. 2023 Feb 23;2023(2):CD015171. doi: 10.1002/14651858.CD015171.pub2

Park 2016.

Study characteristics
Methods Parallel‐group, open‐label RCT with 3 months duration of treatment and follow‐up
Participants Setting:
Multicentre trial conducted at 9 sites in Korea. Study dates were not reported. 
Sample size:

  • Number randomised: 220 participants

  • Number completed: 187 participants


Participant baseline characteristics

  • Age:

    • Reported for the entire study population: mean 52.39 years (SD 10.99)

  • Gender:

    • Reported for the entire study population: 91 (45%) male: 111 (55%) female

  • Probable/definite Ménière's disease:

    • All participants had definite disease (inclusion criterion)

  • Duration of disease:

    • Not reported

  • Attack frequency at baseline:

    • Isosorbide group: mean 5.14 attacks per 4 weeks (no SD reported)

    • Control group: mean 4.88 attacks per 4 weeks (no SD reported)

  • Hearing loss at baseline:

    • Not reported

  • Measure of tinnitus at baseline:

    • Not reported

  • Number of participants with bilateral disease:

    • Not reported


Inclusion criteria:
Definite Ménière's disease, according to the AAO‐HNS 1995 criteria. A history of vertigo that persists for more than 20 minutes, with 2 or more episodes during the last 3 months. A medical record of hearing loss from a hearing test and tinnitus or aural fullness. Aged between 20 and < 80 years. 
Exclusion criteria:
A history of intratympanic injection or surgical treatment within the last 6 months. Use of the study medication (betahistine or isosorbide) within the last 3 months as a treatment for Ménière's disease.
Diagnosis of Ménière's disease:
AAO‐HNS 1995 criteria for definite Ménière's disease
Interventions Intervention (n = 110 randomised, n = 90 completed)
90 mL isosorbide 3 times daily, after meals (total dose and concentration not stated). The dose could be reduced at the investigator's discretion. It is not reported whether this was necessary, and in how many participants. 
Comparator (n = 110 randomised, n = 97 completed)
No intervention
Background interventions administered to all participants
All participants received betahistine tablets 6 mg 3 times daily (total daily dose 18 mg)
Outcomes Primary outcomes relevant to this review:

  • Improvement in vertigo

    • Not reported

  • Change in vertigo

    • Change in frequency of vertigo was reported as the number of episodes in a 4‐week period

  • Serious adverse events

    • Not apparently systematically assessed or reported; narrative summary of adverse events only


Secondary outcomes relevant to this review:

  • Disease‐specific health‐related quality of life

    • Assessed with the Korean version of the DHI

  • Hearing

    • Assessed with pure tone audiometry at 4 frequencies 

  • Tinnitus 

    • Assessed with the Korean THI

  • Other adverse effects

    • Not apparently systematically assessed or reported; narrative summary of adverse events only


Other outcomes reported in the study:

  • Speech discrimination score

  • Electrocochleography

  • Korean Functional Level Scale

  • Change in frequency of vertigo at 4 weeks
Funding sources Not reported
Declarations of interest The authors declare that there are no potential conflicts of interest
Notes Research integrity checklist:

  • No retractions of expressions of concern were identified

  • No prospective trial registration was identified

  • Limited baseline characteristics were available to compare the 2 groups 

  • Some loss to follow‐up was noted 

  • The study is free from implausible results 

  • Identical numbers of participants were randomised to each group, with no description of blocked randomisation 
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk Comment: no information on random sequence generation was provided. 
Allocation concealment (selection bias) Unclear risk Comment: no information on allocation concealment was provided. 
Blinding of participants and personnel (performance bias)
All outcomes High risk Quote (translated): "We couldn’t conduct a double‐blind method using a placebo due to ethical issues and difficulties in making a placebo".
Comment: open‐label study, no blinding. 
Blinding of outcome assessment (detection bias)
All outcomes High risk Quote (translated): "We couldn’t conduct a double‐blind method using a placebo due to ethical issues and difficulties in making a placebo".
Comment: open‐label study, no blinding of outcome assessors. 
Incomplete outcome data (attrition bias)
All outcomes Low risk Comment: some differential loss to follow‐up (19% in intervention group, compared to 12% in control group) but unlikely to have made a considerable impact on the (continuous) outcome data.
Selective reporting (reporting bias) Unclear risk Comment: study protocol was registered with ClinicalTrials.gov, but we note that the registration took place retrospectively. 
Other bias Low risk Comment: no other concerns identified.