AgitationNCT03554915
Ketamine Versus Midazolam for Prehospital Agitation
An observational study of Agitation, run by Hennepin Healthcare Research Institute at 1 site in United States.
Trial summary
This research study is being done to figure out the best approach to treatment of pre-hospital agitation. It will compare two tiered dosing treatment protocols, one ketamine-based and one midazolam-based. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Agitation
- What is being tested?
- Ketamine-based protocol and Midazolam-based protocol
- Type of treatment
- Injection or infusion
- How many people
- 314 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Aug 2017to 24 Sep 2018
- 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
- No healthy volunteers
- Adult, Older adult
Study population: The study population is all patients over age 18 requiring chemical sedation for transport to the emergency department. Etiologies for agitation may include mental illness, substance abuse, critical illness or undetermined.
Who may be able to join
- Age 18 or older
- Severe agitation (AMSS +2 or +3) or profound agitation (AMSS +4) requiring chemical sedation
- Transport to Hennepin County Medical Center
Who cannot join
- Obviously gravid women
- Patients known or suspected to be less than 18 years of age
- Patients in which stopwatch activation, for safety reasons, is unable to occur
Trial locations and contacts
1 site in 1 country.
United States1 site
Hennepin County Medical Center
Minneapolis, Minnesota, 55415
About this study
This research study is being done to figure out the best approach to treatment of pre-hospital agitation. It will compare two tiered dosing treatment protocols, one ketamine-based and one midazolam-based. Agitation is a state of extreme emotional disturbance where patients can become physically aggressive or violent, endangering themselves and those who are caring for them. Often chemical substances or severe mental illness are involved in this level of agitation. Specifically, the investigators are interested in studying agitation that is treated in the prehospital setting by paramedics. This study's hypothesis is a ketamine-based protocol will achieve a faster time to adequate sedation than a midazolam-based protocol for treatment of agitation in the prehospital environment. This study will observe the natural history of an emergency medical services standard operating procedure change from a ketamine-based protocol to a midazolam-based protocol.
- Conditions
- Agitation
- Being tested
- Ketamine-based protocol, Midazolam-based protocol
- Keywords
- Agitation, Ketamine, Midazolam, Emergency Medical Services
- Medical subject headings
- Psychomotor Agitation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketamine-based protocolOther
For profoundly agitated (physically violent) patients, intramuscular ketamine 5 mg/kg will be administered first line. For severely agitated patients, intramuscular ketamine 3 mg/kg will be administered first line.
Midazolam-based protocolOther
For profoundly agitated patients, intramuscular midazolam 15 mg will be administered. For severely agitated patients, intramuscular midazolam 5 mg will be administered.
| Study group | Role | What they receive |
|---|---|---|
| Ketamine-based Protocol | The first 6 month period of the study will employ a ketamine-based protocol for prehospital agitation. There will be a tiered dosing protocol based on degree of agitation. Receives: Other: Ketamine-based protocol | |
| Midazolam-based Protocol | The second 6 month period of the study will employ a midazolam-based protocol for prehospital agitation. There will again be a tiered dosing protocol based on degree of agitation. Receives: Other: Midazolam-based protocol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time from injection of drug to adequate sedation, defined as a score of +1 or less on the AMSS
The Altered Mental Status Scale (AMSS) is an integral ordinal scale evaluating both agitation and sedation with scores from -4 to +4. It was developed at our institution and has been internally and externally validated. This scale is a modified version of the Behavioral Activity Rating Scale with additional data points from the Observer's Assessment of Alertness Scale. Effectiveness of sedation will be defined as an AMSS score less than or equal to +1.
AMSS will be determined by the treating paramedic, who will undergo training as a research associate prior to commencement of the study. Participants will be followed for the duration of agitation, an expected average of 2 hours.
Measured: 2 hours
Secondary outcomes (6)
Number of participants intubated
Participants will be followed for the duration of agitation, an expected average of 2 hours. Enrolling paramedics or research associates in the Emergency Department will record if the patient is intubated.
Measured: 2 hours
Number of participants experiencing hypersalivation
Participants will be followed for the duration of agitation, an expected average of 2 hours. Enrolling paramedics or research associates in the Emergency Department will record if the patient experiences hypersalivation.
Measured: 2 hours
Number of participants experiencing apnea
Participants will be followed for the duration of agitation, an expected average of 2 hours. Enrolling paramedics or research associates in the Emergency Department will record if the patient experiences apnea, defined as 6 seconds of absent EtCO2 waveform.
Measured: 2 hours
Number of participants experiencing nausea/vomiting
Participants will be followed for the duration of agitation, an expected average of 2 hours. Enrolling paramedics or research associates in the Emergency Department will record if the patient experiences nausea/vomiting
Measured: 2 hours
Number of participants experiencing laryngospasm
Participants will be followed for the duration of agitation, an expected average of 2 hours. Enrolling paramedics or research associates in the Emergency Department will record if laryngospasm occurs.
Measured: 2 hours
Number of participants needing rescue sedation
Participants will be followed for the duration of agitation, an expected average of 2 hours. Enrolling paramedics or research associates in the Emergency Department will record if additional sedatives are needed in the prehospital or ED environment.
Measured: 2 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2018
- Study start1 Aug 2017
- Primary completion25 Jun 2018
- Study completion24 Sep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (24)Papers the sponsor has linked to this study.
- Other trials for AgitationStudies 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
- 314 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hennepin Healthcare Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03554915
- Sponsor's protocol ID
- HSR #17-4306
- Status last verified
- Apr 2019
- First submitted
- 29 May 2018
- Last updated
- 5 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Cole JB, Klein LR, Nystrom PC, Moore JC, Driver BE, Fryza BJ, Harrington J, Ho JD. A prospective study of ketamine as primary therapy for prehospital profound agitation. Am J Emerg Med. 2018 May;36(5):789-796. doi: 10.1016/j.ajem.2017.10.022. Epub 2017 Oct 7.
PubMed 29033344Olives TD, Nystrom PC, Cole JB, Dodd KW, Ho JD. Intubation of Profoundly Agitated Patients Treated with Prehospital Ketamine. Prehosp Disaster Med. 2016 Dec;31(6):593-602. doi: 10.1017/S1049023X16000819. Epub 2016 Sep 19.
PubMed 27640730Cole JB, Moore JC, Nystrom PC, Orozco BS, Stellpflug SJ, Kornas RL, Fryza BJ, Steinberg LW, O'Brien-Lambert A, Bache-Wiig P, Engebretsen KM, Ho JD. A prospective study of ketamine versus haloperidol for severe prehospital agitation. Clin Toxicol (Phila). 2016 Aug;54(7):556-62. doi: 10.1080/15563650.2016.1177652. Epub 2016 Apr 22.
PubMed 27102743Ho JD, Smith SW, Nystrom PC, Dawes DM, Orozco BS, Cole JB, Heegaard WG. Successful management of excited delirium syndrome with prehospital ketamine: two case examples. Prehosp Emerg Care. 2013 Apr-Jun;17(2):274-9. doi: 10.3109/10903127.2012.729129. Epub 2012 Dec 11.
PubMed 23231451TREC Collaborative Group. Rapid tranquillisation for agitated patients in emergency psychiatric rooms: a randomised trial of midazolam versus haloperidol plus promethazine. BMJ. 2003 Sep 27;327(7417):708-13. doi: 10.1136/bmj.327.7417.708.
PubMed 14512476Page CB, Parker LE, Rashford SJ, Bosley E, Isoardi KZ, Williamson FE, Isbister GK. A Prospective Before and After Study of Droperidol for Prehospital Acute Behavioral Disturbance. Prehosp Emerg Care. 2018 Nov-Dec;22(6):713-721. doi: 10.1080/10903127.2018.1445329. Epub 2018 Mar 20.
PubMed 29558224Isbister GK, Calver LA, Page CB, Stokes B, Bryant JL, Downes MA. Randomized controlled trial of intramuscular droperidol versus midazolam for violence and acute behavioral disturbance: the DORM study. Ann Emerg Med. 2010 Oct;56(4):392-401.e1. doi: 10.1016/j.annemergmed.2010.05.037.
PubMed 20868907Scaggs TR, Glass DM, Hutchcraft MG, Weir WB. Prehospital Ketamine is a Safe and Effective Treatment for Excited Delirium in a Community Hospital Based EMS System. Prehosp Disaster Med. 2016 Oct;31(5):563-9. doi: 10.1017/S1049023X16000662. Epub 2016 Aug 12.
PubMed 27517801Martel M, Miner J, Fringer R, Sufka K, Miamen A, Ho J, Clinton J, Biros M. Discontinuation of droperidol for the control of acutely agitated out-of-hospital patients. Prehosp Emerg Care. 2005 Jan-Mar;9(1):44-8. doi: 10.1080/10903120590891723.
PubMed 16036827Keseg D, Cortez E, Rund D, Caterino J. The Use of Prehospital Ketamine for Control of Agitation in a Metropolitan Firefighter-based EMS System. Prehosp Emerg Care. 2015 January-March;19(1):110-115. doi: 10.3109/10903127.2014.942478. Epub 2014 Aug 25.
PubMed 25153713Hollis GJ, Keene TM, Ardlie RM, Caldicott DG, Stapleton SG. Prehospital ketamine use by paramedics in the Australian Capital Territory: A 12 month retrospective analysis. Emerg Med Australas. 2017 Feb;29(1):89-95. doi: 10.1111/1742-6723.12685. Epub 2016 Oct 3.
PubMed 27699989Isenberg DL, Jacobs D. Prehospital Agitation and Sedation Trial (PhAST): A Randomized Control Trial of Intramuscular Haloperidol versus Intramuscular Midazolam for the Sedation of the Agitated or Violent Patient in the Prehospital Environment. Prehosp Disaster Med. 2015 Oct;30(5):491-5. doi: 10.1017/S1049023X15004999. Epub 2015 Sep 1.
PubMed 26323511Scheppke KA, Braghiroli J, Shalaby M, Chait R. Prehospital use of i.m. ketamine for sedation of violent and agitated patients. West J Emerg Med. 2014 Nov;15(7):736-41. doi: 10.5811/westjem.2014.9.23229. Epub 2014 Nov 11.
PubMed 25493111Cole JB, Driver BE, Klein LR, Moore JC, Nystrom PC, Ho JD. In reply: Ketamine is an important therapy for prehospital agitation - Its exact role and side effect profile are still undefined. Am J Emerg Med. 2018 Mar;36(3):502-503. doi: 10.1016/j.ajem.2017.12.014. Epub 2017 Dec 7. No abstract available.
PubMed 29229535Linder LM, Ross CA, Weant KA. Ketamine for the Acute Management of Excited Delirium and Agitation in the Prehospital Setting. Pharmacotherapy. 2018 Jan;38(1):139-151. doi: 10.1002/phar.2060. Epub 2017 Dec 22.
PubMed 29136301
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ketamine Versus Midazolam for Prehospital Agitation
- ClinicalTrials.gov ID
- NCT03554915
- Acronym / sponsor ID
- HSR #17-4306
- Conditions
- Agitation
- Keywords
- Agitation, Ketamine, Midazolam, Emergency Medical Services
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 314 participants (actual)
- Lead sponsor
- Hennepin Healthcare Research InstituteUniversity, hospital or other
- Study start
- 1 Aug 2017 (actual)
- Primary completion
- 25 Jun 2018 (actual)
- Study completion
- 24 Sep 2018 (actual)
- First posted
- 13 Jun 2018 (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.
This research study is being done to figure out the best approach to treatment of pre-hospital agitation. It will compare two tiered dosing treatment protocols, one ketamine-based and one midazolam-based. Agitation is a state of extreme emotional disturbance where patients can become physically aggressive or violent, endangering themselves and those who are caring for them. Often chemical substances or severe mental illness are involved in this level of agitation. Specifically, the investigators are interested in studying agitation that is treated in the prehospital setting by paramedics. This study's hypothesis is a ketamine-based protocol will achieve a faster time to adequate sedation than a midazolam-based protocol for treatment of agitation in the prehospital environment. This study will observe the natural history of an emergency medical services standard operating procedure change from a ketamine-based protocol to a midazolam-based protocol.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ketamine-based Protocol | – | Other: Ketamine-based protocolThe first 6 month period of the study will employ a ketamine-based protocol for prehospital agitation. There will be a tiered dosing protocol based on degree of agitation. |
| Midazolam-based Protocol | – | Other: Midazolam-based protocolThe second 6 month period of the study will employ a midazolam-based protocol for prehospital agitation. There will again be a tiered dosing protocol based on degree of agitation. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The study population is all patients over age 18 requiring chemical sedation for transport to the emergency department. Etiologies for agitation may include mental illness, substance abuse, critical illness or undetermined.
Key inclusion criteria (3 listed)
- Age 18 or older
- Severe agitation (AMSS +2 or +3) or profound agitation (AMSS +4) requiring chemical sedation
- Transport to Hennepin County Medical Center
Key exclusion criteria (3 listed)
- Obviously gravid women
- Patients known or suspected to be less than 18 years of age
- Patients in which stopwatch activation, for safety reasons, is unable to occur
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 |
|---|---|---|
| Ketamine-based protocolFor profoundly agitated (physically violent) patients, intramuscular ketamine 5 mg/kg will be administered first line. For severely agitated patients, intramuscular ketamine 3 mg/kg will be administered first line. | Other | Ketamine-based Protocol |
| Midazolam-based protocolFor profoundly agitated patients, intramuscular midazolam 15 mg will be administered. For severely agitated patients, intramuscular midazolam 5 mg will be administered. | Other | Midazolam-based Protocol |
Primary outcome
Time from injection of drug to adequate sedation, defined as a score of +1 or less on the AMSS
Time frame: 2 hours
The Altered Mental Status Scale (AMSS) is an integral ordinal scale evaluating both agitation and sedation with scores from -4 to +4. It was developed at our institution and has been internally and externally validated. This scale is a modified version of the Behavioral Activity Rating Scale with additional data points from the Observer's Assessment of Alertness Scale. Effectiveness of sedation will be defined as an AMSS score less than or equal to +1. AMSS will be determined by the treating paramedic, who will undergo training as a research associate prior to commencement of the study. Participants will be followed for the duration of agitation, an expected average of 2 hours.
6 secondary outcomes
Number of participants intubated
Time frame: 2 hours
Number of participants experiencing hypersalivation
Time frame: 2 hours
Number of participants experiencing apnea
Time frame: 2 hours
Number of participants experiencing nausea/vomiting
Time frame: 2 hours
Number of participants experiencing laryngospasm
Time frame: 2 hours
Number of participants needing rescue sedation
Time frame: 2 hours
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 5 Apr 2019.
- Background: PubMed 29033344Cole JB, Klein LR, Nystrom PC, Moore JC, Driver BE, Fryza BJ, Harrington J, Ho JD. A prospective study of ketamine as primary therapy for prehospital profound agitation. Am J Emerg Med. 2018 May;36(5):789-796. doi: 10.1016/j.ajem.2017.10.022. Epub 2017 Oct 7.
- Background: PubMed 27640730Olives TD, Nystrom PC, Cole JB, Dodd KW, Ho JD. Intubation of Profoundly Agitated Patients Treated with Prehospital Ketamine. Prehosp Disaster Med. 2016 Dec;31(6):593-602. doi: 10.1017/S1049023X16000819. Epub 2016 Sep 19.
- Background: PubMed 27102743Cole JB, Moore JC, Nystrom PC, Orozco BS, Stellpflug SJ, Kornas RL, Fryza BJ, Steinberg LW, O'Brien-Lambert A, Bache-Wiig P, Engebretsen KM, Ho JD. A prospective study of ketamine versus haloperidol for severe prehospital agitation. Clin Toxicol (Phila). 2016 Aug;54(7):556-62. doi: 10.1080/15563650.2016.1177652. Epub 2016 Apr 22.
- Background: PubMed 23231451Ho JD, Smith SW, Nystrom PC, Dawes DM, Orozco BS, Cole JB, Heegaard WG. Successful management of excited delirium syndrome with prehospital ketamine: two case examples. Prehosp Emerg Care. 2013 Apr-Jun;17(2):274-9. doi: 10.3109/10903127.2012.729129. Epub 2012 Dec 11.
- Background: PubMed 14512476TREC Collaborative Group. Rapid tranquillisation for agitated patients in emergency psychiatric rooms: a randomised trial of midazolam versus haloperidol plus promethazine. BMJ. 2003 Sep 27;327(7417):708-13. doi: 10.1136/bmj.327.7417.708.
- Background: PubMed 29558224Page CB, Parker LE, Rashford SJ, Bosley E, Isoardi KZ, Williamson FE, Isbister GK. A Prospective Before and After Study of Droperidol for Prehospital Acute Behavioral Disturbance. Prehosp Emerg Care. 2018 Nov-Dec;22(6):713-721. doi: 10.1080/10903127.2018.1445329. Epub 2018 Mar 20.
- Background: PubMed 20868907Isbister GK, Calver LA, Page CB, Stokes B, Bryant JL, Downes MA. Randomized controlled trial of intramuscular droperidol versus midazolam for violence and acute behavioral disturbance: the DORM study. Ann Emerg Med. 2010 Oct;56(4):392-401.e1. doi: 10.1016/j.annemergmed.2010.05.037.
- Background: PubMed 27517801Scaggs TR, Glass DM, Hutchcraft MG, Weir WB. Prehospital Ketamine is a Safe and Effective Treatment for Excited Delirium in a Community Hospital Based EMS System. Prehosp Disaster Med. 2016 Oct;31(5):563-9. doi: 10.1017/S1049023X16000662. Epub 2016 Aug 12.
- Background: PubMed 16036827Martel M, Miner J, Fringer R, Sufka K, Miamen A, Ho J, Clinton J, Biros M. Discontinuation of droperidol for the control of acutely agitated out-of-hospital patients. Prehosp Emerg Care. 2005 Jan-Mar;9(1):44-8. doi: 10.1080/10903120590891723.
- Background: PubMed 25153713Keseg D, Cortez E, Rund D, Caterino J. The Use of Prehospital Ketamine for Control of Agitation in a Metropolitan Firefighter-based EMS System. Prehosp Emerg Care. 2015 January-March;19(1):110-115. doi: 10.3109/10903127.2014.942478. Epub 2014 Aug 25.
- Background: PubMed 27699989Hollis GJ, Keene TM, Ardlie RM, Caldicott DG, Stapleton SG. Prehospital ketamine use by paramedics in the Australian Capital Territory: A 12 month retrospective analysis. Emerg Med Australas. 2017 Feb;29(1):89-95. doi: 10.1111/1742-6723.12685. Epub 2016 Oct 3.
- Background: PubMed 26323511Isenberg DL, Jacobs D. Prehospital Agitation and Sedation Trial (PhAST): A Randomized Control Trial of Intramuscular Haloperidol versus Intramuscular Midazolam for the Sedation of the Agitated or Violent Patient in the Prehospital Environment. Prehosp Disaster Med. 2015 Oct;30(5):491-5. doi: 10.1017/S1049023X15004999. Epub 2015 Sep 1.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
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, 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 3 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 5 Apr 2019. 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?
Time from injection of drug to adequate sedation, defined as a score of +1 or less on the AMSS (time frame: 2 hours). 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 NCT03554915, which also lists 24 linked publications.
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 5 Apr 2019.