Rapid Agitation Control With Ketamine in the Emergency Department (RACKED)

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

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.

Study Overview

• Status: Completed
• Conditions: Violent Aggressive Behavior; Ketamine
• Intervention / Treatment: Drug: Ketalar; Drug: Midazolam injection; Drug: Haloperidol

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • St. Paul's Hospital Emergency Department

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 19 - 60 years inclusively;
2. Patients presenting to the emergency department with psychomotor agitation or violent behaviour (RASS score > +3).

Exclusion Criteria:

1. Less than 19 years of age;
2. Greater than 60 years of age;
3. Previous participation in this study;
4. Women suspected or known to be pregnant or breastfeeding;
5. Previous known hypersensitivity, intolerance or allergy to ketamine, midazolam or haloperidol or their components.
6. Subjects who are in comatose states or have CNS depression due to alcohol or are taking other depressant drugs.
7. Subjects with severe depressive states, spastic diseases and in Parkinson's syndrome, except in the case of dyskinesias due to levodopa treatment.
8. Senile patients with pre-existing Parkinson-like symptoms.
9. Subjects with a history of cerebrovascular accident
10. Subjects in whom a significant elevation of blood pressure would constitute a serious hazard, such as patients with significant hypertension
11. Subjects with severe cardiac decompensation
12. Subjects who intend to have surgery of the pharynx, larynx, or bronchial tree unless adequate muscle relaxants are used
13. Subjects with acute pulmonary insufficiency
14. Subjects with severe chronic obstructive pulmonary disease
15. Subjects with acute narrow angle glaucoma

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketamine; Single administration of Ketalar® (ketamine hydrochloride injection, USP); 5 mg/kg, IM	Drug: Ketalar; single administration of 5 mg/kg, IM; Other Names: ketamine
Active Comparator: Midazolam + haloperidol; Single administration of combination of: Midazolam injection (5 mg, IM) and haloperidol injection (5mg, IM)	Drug: Midazolam injection; single administration of 5 mg, IM; Drug: Haloperidol; single administration of 5 mg, IM

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: David Barbic
• Collaborators: St Paul's Emergency Department Research Fund; Centre for Health Evaluation and Outcome Sciences (CHÉOS)
• Investigators: Principal Investigator: David Barbic, MD MSc FRCPC,, University of British Columbia

Publications and helpful links

General Publications

• Barbic D, Andolfatto G, Grunau B, Scheuermeyer FX, MacEwan W, Honer WG, Wong H, Barbic SP. Rapid agitation control with ketamine in the emergency department (RACKED): a randomized controlled trial protocol. Trials. 2018 Nov 26;19(1):651. doi: 10.1186/s13063-018-2992-x.

Study record dates

Study Major Dates

• Study Start (Actual): May 29, 2018
• Primary Completion (Actual): March 12, 2020
• Study Completion (Actual): March 12, 2020

Study Registration Dates

• First Submitted: December 12, 2017
• First Submitted That Met QC Criteria: December 12, 2017
• First Posted (Actual): December 18, 2017

Study Record Updates

• Last Update Posted (Actual): November 30, 2020
• Last Update Submitted That Met QC Criteria: November 26, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: midazolam; ketamine; aggressive behaviour; haloperidol; emergency department
• Additional Relevant MeSH Terms: Behavioral Symptoms; Pathologic Processes; Disease Attributes; Aggression; Emergencies; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Antiemetics; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Dopamine Agents; Dopamine Antagonists; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Anti-Dyskinesia Agents; Ketamine; Midazolam; Haloperidol; Haloperidol decanoate
• Other Study ID Numbers: H17-00571

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No