Oral Olanzapine Versus Haloperidol or Diazepam

Study Overview
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Brief Summary
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The purpose of this study is to determine whether oral olanzapine is safer (fewer adverse events) and more effective (shorter time to sedation) than conventional haloperidol or diazepam when used in the management of acute agitation in the emergency.

Detailed Description
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Investigate oral use of sedating drugs within a predominantly Chinese population, to address this void in international literature impacting the management of acute agitation. The multi-centre Randomised Clinical Trial will determine the safety and efficacy of oral olanzapine, in comparison with conventional medicines (haloperidol or diazepam) in a three-arm comparison for the sedation of acutely agitated patients in AEDs. Specifically, we aim to determine if administration of oral olanzapine (a)is more effective than sedation with oral haloperidol or oral diazepam alone; (b)is safer than sedation with comparison arms; (c)decreases the amount of subsequent redosing or alternative drugs required; (d)is more favourable than the haloperidol and diazepam arms with respect to safety, efficacy and adverse events. Investigate potential variables leading to AED attendance and/or admission requiring oral sedation. These may include patient demographic and regular medications and adherence.

Official Title
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Oro-dispersible Olanzapine (Wafer) Versus Conventional Oral Haloperidol or Diazepam Tablets for the Management of Acute Agitation in the Accident and Emergency Department - a Multicentre Randomised Clinical Trial

Conditions
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Acute Agitation, Behavioural Emergency

Intervention / Treatment
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* Drug: Olanzapine oro-dispersible 5Mg Tab
* Drug: Haloperidol 2Mg encapsulated Tab
* Drug: Diazepam 2Mg encapsulated Tab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Accident & Emergency Department patients Requiring oral drug sedation (as determined by an emergency clinician) will be enrolled. Exclusion Criteria: known hypersensitivity or contraindication to the study drugs reversible aetiology for agitation (e.g. hypotension, hypoxia, hypoglycaemia) known pregnancy acute alcohol withdrawal refusal to take oral medication patients from correctional facilities

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Olanzapine<br>oro-dispersible tablet (wafer)(Zyprexa), 5 mg, single dose | Drug: Olanzapine oro-dispersible 5Mg Tab<br>* Patient allocated to this arm will be given 5 mg olanzapine oro-dispersible tablet and an encapsulated placebo tablet<br>* Other names: Zyprexa;|
| Active Comparator: Haloperidol<br>Haloperidol encapsulated tablet, 2 mg tablet, single dose | Drug: Haloperidol 2Mg encapsulated Tab<br>* Patient allocated to this arm will be given 2 mg encapsulated haloperidol tablet and an oro-dispersible placebo tablet<br>|
| Active Comparator: Diazepam<br>Diazepam encapsulated tablet, 2mg tablet, single dose | Drug: Diazepam 2Mg encapsulated Tab<br>* Patient allocated to this arm will be given 2 mg encapsulated diazepam tablet and an oro-dispersible placebo tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to achieve adequate sedation | Adequate sedation is determined by a 6-point validated scale | Within 60 minutes from drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total study drug doses administered; alternative drugs and doses used |  | From Accident & Emergency Department(AED) admission to transfer or discharge from AED, an expected average of 1 hour | 
| Corrected QT interval (QTc) |  | From Accident & Emergency Department(AED) admission to transfer or discharge from AED, an expected average of 1 hour | 
| AED length of stay (LOS) |  | From Accident & Emergency Department(AED) admission to transfer or discharge from AED, an expected average of 1 hour | 
| Adverse events | including airway management (jaw thrust, oral, nasal airway), need for assisted ventilation (bag/mask, intubation), oxygen desaturation <90%, systolic BP<90 mmHg, dystonic reactions, seizures, vomiting or aspiration | From Accident & Emergency Department(AED) admission to transfer or discharge from AED, an expected average of 1 hour | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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emergency, emergency medicine, sedation, acute agitation