Oral Olanzapine Versus Haloperidol or Diazepam

Overview

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

Full Title of Study: “Oro-dispersible Olanzapine (Wafer) Versus Conventional Oral Haloperidol or Diazepam Tablets for the Management of Acute Agitation in the Accident and Emergency Department – a Multicentre Randomised Clinical Trial”

Study Type

• Study Type: Interventional
• Study Design
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Primary Purpose: Treatment
  • Masking: Triple (Participant, Care Provider, Investigator)
• Study Primary Completion Date: June 1, 2018

Detailed Description

1. Investigate oral use of sedating drugs within a predominantly Chinese population, to address this void in international literature impacting the management of acute agitation. 2. The multi-centre Randomised Clinical Trial will determine the safety and efficacy of oral olanzapine, in comparison with conventional medicines (haloperidol or diazepam) in a three-arm comparison for the sedation of acutely agitated patients in AEDs. Specifically, we aim to determine if administration of oral olanzapine (a)is more effective than sedation with oral haloperidol or oral diazepam 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 diazepam arms with respect to safety, efficacy and adverse events. Investigate potential variables leading to AED attendance and/or admission requiring oral sedation. These may include patient demographic and regular medications and adherence.

Interventions

• Drug: Olanzapine oro-dispersible 5Mg Tab
  • Patient allocated to this arm will be given 5 mg olanzapine oro-dispersible tablet and an encapsulated placebo tablet
• Drug: Haloperidol 2Mg encapsulated Tab
  • Patient allocated to this arm will be given 2 mg encapsulated haloperidol tablet and an oro-dispersible placebo tablet
• Drug: Diazepam 2Mg encapsulated Tab
  • Patient allocated to this arm will be given 2 mg encapsulated diazepam tablet and an oro-dispersible placebo tablet

Arms, Groups and Cohorts

• Experimental: Olanzapine
  • oro-dispersible tablet (wafer)(Zyprexa), 5 mg, single dose
• Active Comparator: Haloperidol
  • Haloperidol encapsulated tablet, 2 mg tablet, single dose
• Active Comparator: Diazepam
  • Diazepam encapsulated tablet, 2mg tablet, single dose

Clinical Trial Outcome Measures

Primary Measures

• Time to achieve adequate sedation
  • Time Frame: Within 60 minutes from drug administration
  • Adequate sedation is determined by a 6-point validated scale

Secondary Measures

• Total study drug doses administered; alternative drugs and doses used
  • Time Frame: From Accident & Emergency Department(AED) admission to transfer or discharge from AED, an expected average of 1 hour
• Corrected QT interval (QTc)
  • Time Frame: From Accident & Emergency Department(AED) admission to transfer or discharge from AED, an expected average of 1 hour
• AED length of stay (LOS)
  • Time Frame: From Accident & Emergency Department(AED) admission to transfer or discharge from AED, an expected average of 1 hour
• Adverse events
  • Time Frame: From Accident & Emergency Department(AED) admission to transfer or discharge from AED, an expected average of 1 hour
  • including airway management (jaw thrust, oral, nasal airway), need for assisted ventilation (bag/mask, intubation), oxygen desaturation <90%, systolic BP<90 mmHg, dystonic reactions, seizures, vomiting or aspiration

Participating in This Clinical Trial

Inclusion Criteria

• Accident & Emergency Department patients – Requiring oral drug sedation (as determined by an emergency clinician) will be enrolled. Exclusion Criteria:

• known hypersensitivity or contraindication to the study drugs – reversible aetiology for agitation (e.g. hypotension, hypoxia, hypoglycaemia) – known pregnancy – acute alcohol withdrawal – refusal to take oral medication – patients from correctional facilities

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 75 Years

Are Healthy Volunteers Accepted: No

Investigator Details

• Lead Sponsor
  • The University of Hong Kong
• Collaborator
  • Queen Elizabeth Hospital, Hong Kong
• Provider of Information About this Clinical Study
  • Principal Investigator: Dr. Esther Wai Yin Chan, Associate Professor – The University of Hong Kong

References

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.

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.

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.

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.

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.

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.

Chan EW, Tang C, Lao KS, Ling Pong L, Tsui MS, Ho HF, Wong GC, Kong DC, McD Taylor D, Knott JC, Wong IC. Management of acute agitation in Hong Kong and comparisons with Australasia. Emerg Med Australas. 2015 Dec;27(6):542-548. doi: 10.1111/1742-6723.12499. Epub 2015 Dec 3.

Yap CYL, Taylor DM, Knott JC, Taylor SE, Phillips GA, Karro J, Chan EW, Kong DCM, Castle DJ. Intravenous midazolam-droperidol combination, droperidol or olanzapine monotherapy for methamphetamine-related acute agitation: subgroup analysis of a randomized controlled trial. Addiction. 2017 Jul;112(7):1262-1269. doi: 10.1111/add.13780. Epub 2017 Feb 28.