Agitation,PsychomotorMOHZANCT03211897
Olanzapine, Haloperidol, Ziprasidone, Midazolam for Acute Undifferentiated Agitation
An observational study of Agitation,Psychomotor, run by Hennepin Healthcare Research Institute at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Agitation,Psychomotor
- What is being tested?
- Haloperidol Injection, Ziprasidone Injection and OLANZapine Injection
- Type of treatment
- Injection or infusion
- How many people
- 737 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Jun 2017to 1 Oct 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Adult, Older adult
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.
Who may be able to join
- Emergency Department patients (18+) with acute undifferentiated agitation requiring chemical sedation at the discretion of the attending emergency physician
Who cannot join
- Known pregnancy
- Allergy to the medication during the block
- Prisoner/under arrest
Trial locations and contacts
1 site in 1 country.
United States1 site
Hennepin County Medical Center
Minneapolis, Minnesota, 55415
About this study
Official title: 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.
Read the 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.
- Conditions
- Agitation,Psychomotor
- Being tested
- Haloperidol Injection, Ziprasidone Injection, OLANZapine Injection, Midazolam injection
- Medical subject headings
- Psychomotor Agitation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Haloperidol InjectionDrug
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 InjectionDrug
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 InjectionDrug
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 injectionDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Haloperidol Injection | |
| 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. Receives: Drug: Ziprasidone Injection | |
| 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. Receives: Drug: OLANZapine Injection | |
| 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. Receives: Drug: Midazolam injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 15 minutes
Secondary outcomes (2)
Time to adequate sedation
The time elapsed in minutes to achieve a score of < 1 on a validated agitation scale called the AMSS
Measured: Within the 120 minutes post-medication administration
Rescue Sedation
Proportion of patients requiring additional medication for sedation within 1 hour
Measured: 1 hour
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jul 2017
- Study start15 Jun 2017
- Primary completion1 Oct 2017
- Study completion1 Oct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Agitation,PsychomotorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 737 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hennepin Healthcare Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lauren Klein, MD, Principal investigator, Hennepin County Medical Center, Minneapolis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03211897
- Sponsor's protocol ID
- HSR # 17-4345
- Acronym
- MOHZA
- Status last verified
- Mar 2018
- First submitted
- 26 Jun 2017
- Last updated
- 16 Mar 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 29885904
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Observational Investigation of Olanzapine Versus Haloperidol Versus Ziprasidone Versus Midazolam for the Treatment of Acute Undifferentiated Agitation in the Emergency Department
- ClinicalTrials.gov ID
- NCT03211897
- Acronym / sponsor ID
- MOHZA / HSR # 17-4345
- Conditions
- Agitation,Psychomotor
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 737 participants (actual)
- Lead sponsor
- Hennepin Healthcare Research InstituteUniversity, hospital or other
- Study start
- 15 Jun 2017 (actual)
- Primary completion
- 1 Oct 2017 (actual)
- Study completion
- 1 Oct 2017 (actual)
- First posted
- 7 Jul 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Haloperidol 5mg Intramuscular | – | Drug: Haloperidol InjectionAs 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 | – | Drug: Ziprasidone InjectionAs 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 | – | Drug: OLANZapine InjectionAs 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 | – | Drug: Midazolam injectionAs 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (1 listed)
- Emergency Department patients (18+) with acute undifferentiated agitation requiring chemical sedation at the discretion of the attending emergency physician
Key exclusion criteria (3 listed)
- Known pregnancy
- Allergy to the medication during the block
- Prisoner/under arrest
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Haloperidol InjectionAs 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 5mg Intramuscular |
| Ziprasidone InjectionAs 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 20mg Intramuscular |
| OLANZapine InjectionAs 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 10mg Intramuscular |
| Midazolam injectionAs 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 5mg Intramuscular |
Primary outcome
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.
Time frame: 15 minutes
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.
2 secondary outcomes
Time to adequate sedation
Time frame: Within the 120 minutes post-medication administration
Rescue Sedation
Time frame: 1 hour
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Mar 2018.
- Derived from this study: PubMed 29885904Klein 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.
- Individual participant dataSharing planned: No
Related trials for Agitation,Psychomotor
RecruitingPhase 3
Nabilone for Agitation Blinded Intervention Trial
Alzheimer Disease, Agitation
Not yet recruitingPhase 1
Pharmacokinetics and Relative Bioavailability of Intranasal vs Intramuscular Olanzapine in Healthy Adult Participants
Healthy Adult Participants
Active, not recruiting
Weighted Blankets for Agitation in Adults in the Intensive Care Unit
Psychomotor Agitation, Critical Illness
RecruitingPhase 3
A Phase 3 Study to Evaluate the Safety and Efficacy of KarXT + KarX-EC for the Treatment of Agitation Associated With Alzheimer's Disease
Alzheimer's Disease
Not yet recruitingPhase 2
Inhibition of Aggressive Behavior in Participants With Fragile X Syndrome
Aggressive Behavior in Fragile X Syndome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lauren Klein, MD principal investigator
Hennepin County Medical Center, Minneapolis
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Agitation,Psychomotor, run by Hennepin Healthcare Research Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: 15 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03211897, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Mar 2018.