Rapid Agitation Control With Ketamine in the Emergency Department

Study Overview
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Brief Summary
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Compare intramuscular (IM) ketamine to a combination of IM midazolam and haloperidol with regards to the time required for adequate behavioral control, in minutes, in patients presenting to the emergency department with psychomotor agitation and violent behavior.

Official Title
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Rapid Agitation Control With Ketamine in the Emergency Department (RACKED): a Randomized Controlled Trial

Conditions
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Violent Aggressive Behavior, Ketamine

Intervention / Treatment
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* Drug: Ketalar
* Drug: Midazolam injection
* Drug: Haloperidol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 19 - 60 years inclusively; Patients presenting to the emergency department with psychomotor agitation or violent behaviour (RASS score > +3). Exclusion Criteria: Less than 19 years of age; Greater than 60 years of age; Previous participation in this study; Women suspected or known to be pregnant or breastfeeding; Previous known hypersensitivity, intolerance or allergy to ketamine, midazolam or haloperidol or their components. Subjects who are in comatose states or have CNS depression due to alcohol or are taking other depressant drugs. Subjects with severe depressive states, spastic diseases and in Parkinson's syndrome, except in the case of dyskinesias due to levodopa treatment. Senile patients with pre-existing Parkinson-like symptoms. Subjects with a history of cerebrovascular accident Subjects in whom a significant elevation of blood pressure would constitute a serious hazard, such as patients with significant hypertension Subjects with severe cardiac decompensation Subjects who intend to have surgery of the pharynx, larynx, or bronchial tree unless adequate muscle relaxants are used Subjects with acute pulmonary insufficiency Subjects with severe chronic obstructive pulmonary disease Subjects with acute narrow angle glaucoma

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 60 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: Ketamine<br>Single administration of Ketalar® (ketamine hydrochloride injection, USP); 5 mg/kg, IM | Drug: Ketalar<br>* single administration of 5 mg/kg, IM<br>* Other names: ketamine;|
| Active Comparator: Midazolam + haloperidol<br>Single administration of combination of: Midazolam injection (5 mg, IM) and haloperidol injection (5mg, IM) | Drug: Midazolam injection<br>* single administration of 5 mg, IM<br>Drug: Haloperidol<br>* single administration of 5 mg, IM<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time from first IM medication administration to adequate sedation which is defined as RASS less than or equal to -1. | Measured using Richmond Agitation Sedation Scale (RASS) in each arm | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage participants with adverse events in each arm | measured by AE collection in each arm | up to 4 days | 
| Percentage of participants in each arm requiring rescue medications between 5 and 30 minutes (at 5 minutes interval) after study medication(s) administration by count. | measured by rescue medication administration | 1 day | 
| Percentage of participants in each arm experiencing sedation outcomes as defined by the TROOPS criteria | measured using Tracking and Reporting Outcomes of Procedural Sedation (TROOPS) criteria | 1 day | 
| Percentage of participants with neuroleptic malignant syndrome events within 24 hours of enrollment of each arm. | measured by occurrence of neuroleptic malignant syndrome | 1 day | 
| Percentage of participants experiencing pre-hospital use of force by police in this participant population, by number and type of restraint. | measured by police account at study enrollment | 1 day | 
| Participant experience survey outcomes. | measured using Participant Experience Survey | 1 day | 
| Study Nurse Experience survey outcomes. | measured using Study Nurse Experience Survey | 1 day | 
| Effectiveness of Blinding survey outcomes | measured using Effectiveness of Study Drug Blinding Survey | 1 day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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haloperidol, emergency department, ketamine, aggressive behaviour, midazolam