Olanzapine, Haloperidol, Ziprasidone, Midazolam for Acute Undifferentiated Agitation (MOHZA)

Prospective Observational Investigation of Olanzapine Versus Haloperidol Versus Ziprasidone Versus Midazolam for the Treatment of Acute Undifferentiated Agitation in the Emergency Department

The goal of this research investigation is to conduct a prospective observational study of the comparative efficacy of haloperidol versus olanzapine versus midazolam versus ziprasidone for the treatment of acute undifferentiated agitation in the emergency department.

Study Overview

• Status: Completed
• Conditions: Agitation,Psychomotor
• Intervention / Treatment: Drug: Haloperidol Injection; Drug: Ziprasidone Injection; Drug: OLANZapine Injection; Drug: Midazolam injection

Detailed Description

The ED will implement a treatment protocol as a quality improvement initiative. All patients requiring chemical sedation for will receive haloperidol as the initial treatment for agitation for 21 days, followed by ziprasidone as the initial treatment for agitation for 21 days, followed by olanzapine as the initial treatment for agitation for 21 days, and finally midazolam as the initial treatment for agitation for 21 days.

This is a clinical care quality improvement protocol. The research component is the observation of this clinical care protocol.

Patients who receive medications in the ED will be observed by research staff, evaluating efficacy and safety of the administered medication. The decision to administer the medication is at the discretion of the physician. Research protocols are only such that we are observing the efficacy and safety, which coincides the quality improvement purposes of this clinical protocol.

Trained Research Associates will collect all data on patients who receive a protocol medication. This will include baseline demographic data including age, gender, etiology of agitation (according to the treating physician, presumed at the time of medication administration), initial vital signs, breath alcohol level, drug screen results, pre-hospital medications administered, and any other laboratory data available at the time (e.g. glucose).

Research associates will record the patient's level of agitation using a validated agitation scale, the Altered Mental Status (AMS scale). The AMS scale is an ordinal scale ranging from -4 (profoundly somnolent) to +4 (profoundly agitated), with agitation generally defined as an AMS scale of 2 or greater. This scale is a modified version of the Observer's Assessment of Alertness Scale and the Behavioral Activity Rating Scale.

AMS scores will be recorded at the time of medication administration and at every subsequent 15-minute interval until 120 minutes. Research associates will also carry stopwatches and record the time elapsed until adequate sedation (defined as an AMS ≤ 0), as well as whether other medications (defined as "rescue medications") were administrated for any reason and at what time this occurred.

Research associates will prospectively monitor each patient for all adverse side effects of the medications, including hypoxia, need for airway intervention (nasal cannula, facemask, non-invasive positive pressure ventilation, endotracheal intubation), hypotension, cardiac dysrhythmias, extrapyramidal side effects, and other complications.

• Study Type: Observational
• Enrollment (Actual): 737

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Emergency Department patients with acute undifferentiated agitation requiring chemical sedation at the discretion of the attending emergency physician. Patients studied are from a population where agitation is predominantly due to alcohol, illicit substances, or psychiatric agitation.

Description

Inclusion Criteria:

• Emergency Department patients (18+) with acute undifferentiated agitation requiring chemical sedation at the discretion of the attending emergency physician

Exclusion Criteria:

• Known pregnancy
• Allergy to the medication during the block
• Prisoner/under arrest

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Haloperidol 5mg Intramuscular; As part of the quality initiative protocol, patients who are treated for acute agitation in the ED will receive haloperidol as their initial sedative agent during the 21 day block. All subsequent agitation medications are at the discretion of the provider.	Drug: Haloperidol Injection; As part of the quality initiative protocol, patients who are treated for acute agitation in the ED will receive haloperidol as their initial sedative agent during the 21 day block. All subsequent agitation medications are at the discretion of the provider.
Ziprasidone 20mg Intramuscular; As part of the quality initiative protocol, patients who are treated for acute agitation in the ED will receive ziprasidone as their initial sedative agent during the 21 day block. All subsequent agitation medications are at the discretion of the provider.	Drug: Ziprasidone Injection; As part of the quality initiative protocol, patients who are treated for acute agitation in the ED will receive ziprasidone as their initial sedative agent during the 21 day block. All subsequent agitation medications are at the discretion of the provider.
Olanzapine 10mg Intramuscular; As part of the quality initiative protocol, patients who are treated for acute agitation in the ED will receive olanzapine as their initial sedative agent during the 21 day block. All subsequent agitation medications are at the discretion of the provider.	Drug: OLANZapine Injection; As part of the quality initiative protocol, patients who are treated for acute agitation in the ED will receive olanzapine as their initial sedative agent during the 21 day block. All subsequent agitation medications are at the discretion of the provider.
Midazolam 5mg Intramuscular; As part of the quality initiative protocol, patients who are treated for acute agitation in the ED will receive midazolam as their initial sedative agent during the 21 day block. All subsequent agitation medications are at the discretion of the provider.	Drug: Midazolam injection; As part of the quality initiative protocol, patients who are treated for acute agitation in the ED will receive midazolam as their initial sedative agent during the 21 day block. All subsequent agitation medications are at the discretion of the provider.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary outcome will be the mean difference in Altered Mental Status (AMS) score from baseline at 15 minutes post-administration for each study drugs.	Patients score on a previously validated agitation scale called the AMSS ADDENDUM: The primary outcome for this study was changed prior to study initiation to the proportion of patients adequately sedated at 15 minutes (defined as AMSS < 1). This addendum was methodologically necessary to account for the ordinal, non-normal distribution of this data.	15 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to adequate sedation	The time elapsed in minutes to achieve a score of < 1 on a validated agitation scale called the AMSS	Within the 120 minutes post-medication administration
Rescue Sedation	Proportion of patients requiring additional medication for sedation within 1 hour	1 hour

Collaborators and Investigators

• Sponsor: Hennepin Healthcare Research Institute
• Investigators: Principal Investigator: Lauren Klein, MD, Hennepin County Medical Center, Minneapolis

Publications and helpful links

General Publications

• Klein LR, Driver BE, Miner JR, Martel ML, Hessel M, Collins JD, Horton GB, Fagerstrom E, Satpathy R, Cole JB. Intramuscular Midazolam, Olanzapine, Ziprasidone, or Haloperidol for Treating Acute Agitation in the Emergency Department. Ann Emerg Med. 2018 Oct;72(4):374-385. doi: 10.1016/j.annemergmed.2018.04.027. Epub 2018 Jun 7.

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2017
• Primary Completion (Actual): October 1, 2017
• Study Completion (Actual): October 1, 2017

Study Registration Dates

• First Submitted: June 26, 2017
• First Submitted That Met QC Criteria: July 6, 2017
• First Posted (Actual): July 7, 2017

Study Record Updates

• Last Update Posted (Actual): March 16, 2018
• Last Update Submitted That Met QC Criteria: March 14, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Dyskinesias; Psychomotor Disorders; Psychomotor Agitation; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Antiemetics; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Dopamine Agents; Serotonin Antagonists; Dopamine Antagonists; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Anti-Dyskinesia Agents; Olanzapine; Midazolam; Ziprasidone; Haloperidol; Haloperidol decanoate
• Other Study ID Numbers: HSR # 17-4345

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No