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Journal Reading

Clinical Study :
Treatment of Vertigo : A Randomized, Double-Blind
Trial Comparing Efficacy and Safety of Ginkgo Biloba Extract
EGb 761 and Betahistine

Consulants:
dr. Bambang Agus Susanto, Sp. THT-KL

Muhammad Iqbal Oktakusuma


(30101307005)
Almira Pratiwi
(30101407128)
ABSTRACT

Objective : EGb 761


Compare the efficacy and safety Patients with vertigo
Betahistine

EGb 761 (240 Outcome


Methode : mg/day) Double-blind measures:
• multicenter study treatment - NAS
- CGIS
• 160 patients Betahistine (32 (12 weeks) - VSS-SF
• randomization mg/day) - SDS
ABSTRACT
• Both treatment groups were comparable at baseline. There was no significant difference in
outcome improvement on both group.
• Numerically EGb 761 has better outcome (76%) .

Result : • Clinical global impression  “very much improved” or “much improved”


• 79% of patients in EGb 761 group
• 70% receiving in betahistine group
• EGb761  27 adverse events in 19 patients, showed better tolerability
• Betahistine39 adverse events in 31 patients.

In conclusion,the two drugs were similarly effective in the treatment of


Conclusion: vertigo, but EGb 761 was better tolerated
INTRODUCTION

Dizziness = most frequently reported symptom in primary care


4%
22.9%
22.9%
4.9%
4869 adults 3.3%
(18-79 y.o)
1.4% (complained
Complained dizziness dizziness )
Cerebrovascular disease
One-year prevalence
Otological/vestibular origin
One-year incidence
Germany E.D in US
Most frequent vertigo
• Central-vestibuslar vertigo (12,4%)
• Bilateral vestibulopathy perifer (5.1%)
• Paroximal Disfunction of the vestibular nerve or vestibular organ
(3.9%)

Cereberovascular disease
• 24% patients who experience compromised blood supply of
vertebrobasilar region manifest as vertigo
• 17% pastients who experience micrangiopathy cerebral as vertigo
Betahistine
Betahistine
Piracetam
Betahistine is a histamine analogue with agonistic
activity at the H1 and antagonistic activity at H3
Egb 761 histamine receptors.
Ginkgo biloba Extract (EGb 761)
Decreasing blood viscosity

Enhances cerebral and vestibular blood flow

Improves neuronal plasticity

Mitocondrial function and methabolism

Protect neuron
Objective

To compare the efficacy and safety of Ginkgo biloba extract


EGb 761 and betahistine at recommended doses in patients
with vertigo.
Patients and Method

• A randomized, placebo-controlled, double-blind, multicenter clinical


trial (outpatient clinics at 10 hospitals in Ukraine).
• The protocol was approved by the ethics committee of the Ministry of
Healthcare of Ukraine and the local ethics committees.
• Informed consent was obtained from all patients before any trial-
related procedures were undertaken.
Patients selection
Inclusion criteria
• Patients of either sex,
• At least 45 years old,
• Diagnosed with peripheral vertigo not other wise specified (H81.3) or vertiginous syndrome
not otherwise specified (H81.9) based on ICD-10
had symptoms of vertigo for at least 3 months,
• Scored at least 3 on a one-to ten numeric analogue scale (NAS) at screening,
• And had sufficient Russian or Ukrainian language skills to respond to interview questions and
complete questionnaires.
• A negative pregnancy test and adequate contraception were required from female patients.
Exclusion criteria
• Specific vertiginous syndromes (e.g., M´eni`ere’s disease, Lermoyez
syndrome, and benign paroxysmal positional vertigo),
• Vertigo due to specified somatic diseases (except cerebrovascular disease),
• Severe other disorders, contraindications to one of the drugs under study,
need for drugs that might interfere with the efficacy assessments, or
gastrointestinal disorders with uncertain absorption of the active agents
were excluded from the study.
Meet the inclusion 160 patients
criteria (≥ 45 years old)

Randomized
Double blinded EGb 761 Betahistine
treatment for 12 N = 80 patients N=80 patients
weeks (16 mg b.i.d) (120 mg b.id)
Visits and Asessment
Eleven-point Numeric Vertigo Symptoms Scale-
Analogue Scale (NAS) Short Form (VSS-SF)
Efficacy
Asessment
Sheehan Disability Clinical Global
Scale (SDS) Impression (CGI)
Assessments of efficacy and safety of the drugs were scheduled 4,8,and 12 weeks after the
baseline visit
Safety Assessment
• To monitor the safety of the treatment vital sign examination
(every visit) and ECG, laboratory test baseline and final,
• Adverse events were recorded 
• Seriousness
• Severity
• Causality
Statistic Analysis
• Descriptive𝑃 values were calculated using Wilcoxon tests and Fisher’s
exact tests for quantitative and categorical parameters, respectively.
• Efficacy analyses were based on the full analysis data set including all
patients who received randomized study treatment at least once and
having at least one measurement of any efficacy parameter during
the randomized treatment period
Results
• 169 patients screened, 160 were
eligile, received treatment as
randomly allocated fully
analyzed EGb 761, 80 patients;
betahistine, 80 patients).
• 3 patients in the EGb 761 group
and 2 patients in the betahistine
group were terminated.
Demographic data, rating scale scores, and clinical neurootological findings at enrollment are presented in Table 1

• There were no conspicuous


differences between the
treatment groups when
treatment was started.
There was no significant intergroup difference with regard to changes in any
outcome measure.
Safety
Discussion

• The patients’ subjective ratings and the physicians’ global impressions


of change were strongly supported by the objective findings from
clinical neurootological examinations:
• Swaying in the Romberg test is decrased
• Rotation in Unterberger’s stepping test were decreased
• Spontaneous nystagmus was no longer found
Efficacy Efficacy

Response rate, defined as CGI rated “much


improved” or “very much improved” or patient’s
rating of NAS improvement’s at least 50%
Efficacy

Proportion of patients with nystagmus before and


after treatment
Efficacy

Proportion of patients with different grades of


swaying in the Romberg test before and after
treatment
Efficacy

Proportion of patients with different grades of


rotation in unterberger’s stepping test
• Both treatments are evidence-based.
• High rates of marked spontaneous improvements are not very likely
after an average duration of symptoms of approximately 2 years,
• Therefore there is a reason to assume that the observed effects are
mostly treatment-related and not mere placebo effects.
• The dosage that were used in this study were chosen from some
previous study and clinical trial that show the effective dose of
Betahistine is 32 mg /day.
• To be involved in the antivertiginous action of EGb 761 deserves attention.
Vertigo and the sensation of dizziness may result from labyrinth dysfunction or
disconnection or impaired processing of information within the central nervous
networks (vestibular, ocular, oculomotor, cortical, and cerebellar) involved in
equilibrium and posture control. Aging-associated loss of cortical neurons and
integrity of fiber tracts as well as a slowing of information processing may
contribute to or enhance such dysfunction. Impaired intrinsic and synaptic
mechanismsof neuronalplasticity are likely to prevent full compensation of
disturbances in the vestibular system and to play a role in long-lastin vertiginous
syndromes. EGb 761 has been shown to enhance neuronal plasticity by
stimulating neurogenesis, neurite outgrowth, synaptogenesis, and synaptic
function . Of note, Lacour and colleagues Observed an accelerated recovery of
synaptic density in the medial vestibular nuclei of EGb761 treated cats after
unilateral vestibular neurectomy.
Safety and tolerability
• EGb 761 seems to have some advantage over betahistine.
• No patients withdrew from treatment due to adverse events,
• The total number of adverse events as well as the number of patients
who experience adverse event was lower in the Egb 761 group than in
the betahistine group
Conclusion
The two drugs were similarly effective in the treatment of vertigo, but
EGb 761 was better tolerated