IM Olanzapine Versus Haloperidol or Midazolam

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

Detailed Description
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To address significant knowledge gaps by several means: Investigate intramuscular use of sedative drugs within a predominantly Chinese population, to address this void in international literature impacting the management of acute agitation. The multi-centre RCT will determine the safety and efficacy of intramuscular olanzapine, in comparison with conventional medicines (haloperidol or midazolam) in a three-arm comparison for the sedation of acutely agitated patients in emergency department. Specifically, we aim to determine if administration of intramuscular olanzapine (a)is more effective than sedation with intramuscular haloperidol or intramuscular midazolam 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 midazolam arms with respect to safety, efficacy and adverse events. Investigate potential variables leading to emergency attendance and/or admission requiring parenteral sedation. These may include patient demographics and regular medications and adherence.

Official Title
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Intramuscular Olanzapine Versus Haloperidol or Midazolam for the Management of Acute Agitation in the Emergency Department - a Multicentre Randomised Clinical Trial

Conditions
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Acute Agitation, Behavioural Emergency

Intervention / Treatment
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* Drug: Olanzapine
* Drug: Haloperidol
* Drug: Midazolam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Emergency Department patients, requiring parenteral drug sedation (as determined by an emergency clinician) will be enrolled. Exclusion Criteria: Patients will be excluded if there are known hypersensitivity or contraindication to the study drugs reversible aetiology for agitation (e.g. hypotension, hypoxia, hypoglycaemia) known pregnancy acute alcohol withdrawal patients aged>75 years.

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>intramuscular olanzapine injection (zyprexa), 5 mg/dose, first dose and an optional second dose. | Drug: Olanzapine<br>* Intramuscular injection<br>* Other names: ZYPREXA;|
| Active Comparator: Haloperidol<br>intramuscular haloperidol injection, 5 mg/dose, first dose and an optional second dose. | Drug: Haloperidol<br>* Intramuscular injection<br>|
| Active Comparator: Midazolam<br>intramuscular midazolam injection, 5 mg/dose, first dose and an optional second dose. | Drug: Midazolam<br>* Intramuscular injection<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 Emergency Department admission to transfer or discharge from AED, an expected average of 1 hour | 
| Prolonged QTc interval |  | From Emergency Department admission to transfer or discharge from Emergency Department, an expected average of 1 hour | 
| AED length of stay (LOS) |  | From Emergency Department admission to transfer or discharge from Emergency Department, 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 Emergency Department admission to transfer or discharge from Emergency Department 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