Clinical trial NCT02380118: IM Olanzapine Versus Haloperidol or Midazolam
Official title: Intramuscular Olanzapine Versus Haloperidol or Midazolam for the Management of Acute Agitation in the Emergency Department - a Multicentre Randomised Clinical Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Acute Agitation, Behavioural Emergency
Keywords: emergency
emergency medicine
sedation
acute agitation
Lead sponsor: The University of Hong Kong
Sponsor class: OTHER
Collaborators: name: Queen Mary Hospital, Hong Kong
name: Tuen Mun Hospital
name: Pamela Youde Nethersole Eastern Hospital
name: Ruttonjee Hospital
name: Prince of Wales Hospital, Shatin, Hong Kong
name: United Christian Hospital
First posted: 2015-03-05
Enrollment: 167
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether intramuscular olanzapine is safer (fewer adverse events) and more effective (shorter time to sedation) than conventional haloperidol or midazolam when used in the management of acute agitation in the emergency department.

Detailed description: To address significant knowledge gaps by several means:

1. Investigate intramuscular use of sedative drugs within a predominantly Chinese population, to address this void in international literature impacting the management of acute agitation.

   The multi-centre RCT will determine the safety and efficacy of intramuscular olanzapine, in comparison with conventional medicines (haloperidol or midazolam) in a three-arm comparison for the sedation of acutely agitated patients in emergency department. Specifically, we aim to determine if administration of intramuscular olanzapine (a)is more effective than sedation with intramuscular haloperidol or intramuscular midazolam alone; (b)is safer than sedation with comparison arms; (c)decreases the amount of subsequent redosing or alternative drugs required; (d)is more favourable than the haloperidol and midazolam arms with respect to safety, efficacy and adverse events.
2. Investigate potential variables leading to emergency attendance and/or admission requiring parenteral sedation. These may include patient demographics and regular medications and adherence.

Eligibility criteria: Inclusion Criteria:

* Emergency Department patients, requiring parenteral drug sedation (as determined by an emergency clinician) will be enrolled.

Exclusion Criteria:

* Patients will be excluded if there are

  1. known hypersensitivity or contraindication to the study drugs
  2. reversible aetiology for agitation (e.g. hypotension, hypoxia, hypoglycaemia)
  3. known pregnancy
  4. acute alcohol withdrawal
  5. patients aged\>75 years.

Primary outcomes:
measure: Time to achieve adequate sedation
timeFrame: Within 60 minutes from drug administration
Secondary outcomes:
measure: Total study drug doses administered; alternative drugs and doses used
timeFrame: From Emergency Department admission to transfer or discharge from AED, an expected average of 1 hour
measure: Prolonged QTc interval
timeFrame: From Emergency Department admission to transfer or discharge from Emergency Department, an expected average of 1 hour
measure: AED length of stay (LOS)
timeFrame: From Emergency Department admission to transfer or discharge from Emergency Department, an expected average of 1 hour
measure: Adverse events
timeFrame: From Emergency Department admission to transfer or discharge from Emergency Department an expected average of 1 hour
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Pamela Youde Nethersole Eastern Hospital
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Hong Kong
country: Hong Kong
facility: Ruttonjee Hospital
city: Hong Kong
country: Hong Kong
facility: Tuen Mun Hospital
city: Hong Kong
country: Hong Kong
facility: United Christian Hospital
Study officials:
affiliation: The University of Hong Kong
name: Esther WY Chan, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Knott JC, Bennett D, Rawet J, Taylor DM. Epidemiology of unarmed threats in the emergency department. Emerg Med Australas. 2005 Aug;17(4):351-8. doi: 10.1111/j.1742-6723.2005.00756.x.
citation: Chan EW, Taylor DM, Knott JC, Phillips GA, Castle DJ, Kong DC. Intravenous droperidol or olanzapine as an adjunct to midazolam for the acutely agitated patient: a multicenter, randomized, double-blind, placebo-controlled clinical trial. Ann Emerg Med. 2013 Jan;61(1):72-81. doi: 10.1016/j.annemergmed.2012.07.118. Epub 2012 Sep 13.
citation: Knott JC, Taylor DM, Castle DJ. Randomized clinical trial comparing intravenous midazolam and droperidol for sedation of the acutely agitated patient in the emergency department. Ann Emerg Med. 2006 Jan;47(1):61-7. doi: 10.1016/j.annemergmed.2005.07.003. Epub 2005 Aug 18.
citation: Chan EW, Taylor DM, Knott JC, Kong DC. Variation in the management of hypothetical cases of acute agitation in Australasian emergency departments. Emerg Med Australas. 2011 Feb;23(1):23-32. doi: 10.1111/j.1742-6723.2010.01348.x. Epub 2010 Nov 22.
citation: Chan EW, Knott JC, Taylor DM, Phillips GA, Kong DC. Intravenous olanzapine--another option for the acutely agitated patient? Emerg Med Australas. 2009 Jun;21(3):241-2. doi: 10.1111/j.1742-6723.2009.01190.x. No abstract available.
citation: Chan EW, Taylor DM, Knott JC, Liew D, Kong DC. The pharmacoeconomics of managing acute agitation in the emergency department: what do we know and how do we approach it? Expert Rev Pharmacoecon Outcomes Res. 2012 Oct;12(5):589-95. doi: 10.1586/erp.12.53.
citation: Chan EW, Lao KSJ, Lam L, Tsui SH, Lui CT, Wong CP, Graham CA, Cheng CH, Chung TS, Lam HF, Ting SM, Knott JC, Taylor DM, Kong DCM, Leung LP, Wong ICK. Intramuscular midazolam, olanzapine, or haloperidol for the management of acute agitation: A multi-centre, double-blind, randomised clinical trial. EClinicalMedicine. 2021 Feb 11;32:100751. doi: 10.1016/j.eclinm.2021.100751. eCollection 2021 Feb.