Comparing Haloperidol and Olanzapine in Treating Terminal Delirium

NCT04750395 | Unknown Phase 2

• 1 other identifier: 21-HALOLAN
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

As patients with terminal illness enter the dying phase, they may experience symptoms of restlessness, agitation, or cognitive disturbance, known as terminal delirium. In community care, pharmacological therapies are utilized to manage the syndrome, the most commonly used being neuroleptics haloperidol and olanzapine. However, there is currently a dearth of studies on the efficacy and safety between haloperidol and olanzapine in the community palliative care setting; existing studies involve non-terminal patients in the hospital suffering from acute delirium. To fill this gap, an open-label randomized clinical trial is proposed to compare the effects of haloperidol and olanzapine in the management of terminal delirium in home hospice patients who are imminently dying. Key outcome measures are the reduction of delirium symptoms and the reduction of agitation. Secondary outcome is comparing the adverse effect burden on patients.

Conditions

Delirium; Terminal Illness

Keywords

Haloperidol; Olanzapine; terminal delirium; home hospice

Outcome Measures

Primary Outcomes (2)

• Severity of agitation, measured by the Memorial Delirium Assessment Scale (MDAS)

  MDAS is a ten-item, four-point clinician-rated scale designed to quantify the severity of delirium in medically-ill patients (range 1 - 40). Items included in the scale reflect the diagnostic criteria for delirium in the DSM-IV. It has very good psychometric proper-ties, with high reliability (r = .91) and good Discriminant and Concurrent validity. Though the scale was intended to assess patients based on all ten items, it was suggested that items in MDAS can be pro-rated in the event the patient is not able to communicate. The higher the score, the more severe the agitation.

  72 hours

• Severity of terminal delirium, measured by the Richmond Agitation-Sedation Scale modified for palliative care (RASS-PAL)

  The RASS is a simple observational instrument assessing levels of sedation and agitation. It requires no patient input and ranges from +4 (overly combative) to -5 (unarousable). It is considered less time-consuming and easier to use than other similar instruments. Developed for adult intensive care unit patients, the scale demonstrated strong inter-rater reliability in that setting. A modified version was de-signed for use in the palliative care setting, which produced acceptable psychometric properties. Hui et. al. (2018) had caregivers using the RASS to assess patients, which gave ratings similar to clinicians.

  72 hours

Secondary Outcomes (1)

• Adverse effects or toxicity, measured by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)

  0-72 hours

Study Arms (2)

Haloperidol

EXPERIMENTAL

Every 24 hours, patients will receive two regular doses of OT Haloperidol 2.5mg. Patients may also receive up to two breakthrough doses within a minimum interval of one hour from the last dose. In total, up to four doses of medication will be prepared.

Drug: Haloperidol Solution

Olanzapine

EXPERIMENTAL

Every 24 hours, patients will receive two regular doses of OT Olanzapine 5.0mg. Patients may also receive up to two breakthrough doses within a minimum interval of one hour from the last dose. In total, up to four doses of medication will be prepared.

Drug: Olanzapine Tablets

Interventions

Haloperidol Solution DRUG

Oral transmucosal haloperidol solution 2.5mg

Haloperidol

Olanzapine Tablets DRUG

Oral transmucosal olanzapine tablet 5.0mg

Olanzapine

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient is above 21 years of age.
• Patient was diagnosed with a terminal illness and is receiving end-of-life care at home.
• Patient is assessed to be acutely dying (estimated prognosis of three days or less).
• Patient is diagnosed with delirium, as described in the DSM-V (American Psychiatric Association, 2013)

You may not qualify if:

• Patient does not have a caregiver at home.
• Patient has a prior history of dementia, psychosis, schizophrenia or any other mental health issue followed up by psychiatrists or other specialists.
• Patient is currently receiving, or has been administered Haloperidol or Olanzapine less than a week before participating in the study.
• Patient has known allergies or adverse reactions to Haloperidol or Olanzapine.
• Patients who survive 7 days after recruitment will be excluded from the study.

Sponsors & Collaborators

• HCA Hospice Care: lead

Study Sites (1)

HCA Hospice Care

Singapore, 328127, Singapore

RECRUITING

Related Publications (20)

• Agar M, Ko DN, Sheehan C, Chapman M, Currow DC. Informed consent in palliative care clinical trials: challenging but possible. J Palliat Med. 2013 May;16(5):485-91. doi: 10.1089/jpm.2012.0422. Epub 2013 Apr 30.

  PMID: 23631612 BACKGROUND

• American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders: DSM-V (5th ed.). Arlington: American Psychiatric Association.

  BACKGROUND

• Bannon L, McGaughey J, Verghis R, Clarke M, McAuley DF, Blackwood B. The effectiveness of non-pharmacological interventions in reducing the incidence and duration of delirium in critically ill patients: a systematic review and meta-analysis. Intensive Care Med. 2019 Jan;45(1):1-12. doi: 10.1007/s00134-018-5452-x. Epub 2018 Nov 30.

  PMID: 30506354 BACKGROUND

• Breitbart W, Rosenfeld B, Roth A, Smith MJ, Cohen K, Passik S. The Memorial Delirium Assessment Scale. J Pain Symptom Manage. 1997 Mar;13(3):128-37. doi: 10.1016/s0885-3924(96)00316-8.

  PMID: 9114631 BACKGROUND

• Bush SH, Grassau PA, Yarmo MN, Zhang T, Zinkie SJ, Pereira JL. The Richmond Agitation-Sedation Scale modified for palliative care inpatients (RASS-PAL): a pilot study exploring validity and feasibility in clinical practice. BMC Palliat Care. 2014 Mar 31;13(1):17. doi: 10.1186/1472-684X-13-17.

  PMID: 24684942 BACKGROUND

• Bush SH, Kanji S, Pereira JL, Davis DHJ, Currow DC, Meagher D, Rabheru K, Wright D, Bruera E, Hartwick M, Gagnon PR, Gagnon B, Breitbart W, Regnier L, Lawlor PG. Treating an established episode of delirium in palliative care: expert opinion and review of the current evidence base with recommendations for future development. J Pain Symptom Manage. 2014 Aug;48(2):231-248. doi: 10.1016/j.jpainsymman.2013.07.018. Epub 2014 Jan 28.

  PMID: 24480529 BACKGROUND

• Bush SH, Leonard MM, Agar M, Spiller JA, Hosie A, Wright DK, Meagher DJ, Currow DC, Bruera E, Lawlor PG. End-of-life delirium: issues regarding recognition, optimal management, and the role of sedation in the dying phase. J Pain Symptom Manage. 2014 Aug;48(2):215-30. doi: 10.1016/j.jpainsymman.2014.05.009. Epub 2014 May 28.

  PMID: 24879997 BACKGROUND

• Casarett DJ, Inouye SK; American College of Physicians-American Society of Internal Medicine End-of-Life Care Consensus Panel. Diagnosis and management of delirium near the end of life. Ann Intern Med. 2001 Jul 3;135(1):32-40. doi: 10.7326/0003-4819-135-1-200107030-00011.

  PMID: 11434730 BACKGROUND

• Finucane AM, Jones L, Leurent B, Sampson EL, Stone P, Tookman A, Candy B. Drug therapy for delirium in terminally ill adults. Cochrane Database Syst Rev. 2020 Jan 21;1(1):CD004770. doi: 10.1002/14651858.CD004770.pub3.

  PMID: 31960954 BACKGROUND

• Gagnon P, Allard P, Gagnon B, Merette C, Tardif F. Delirium prevention in terminal cancer: assessment of a multicomponent intervention. Psychooncology. 2012 Feb;21(2):187-94. doi: 10.1002/pon.1881. Epub 2010 Dec 19.

  PMID: 22271539 BACKGROUND

• Hui D, Dev R, Bruera E. Neuroleptics in the management of delirium in patients with advanced cancer. Curr Opin Support Palliat Care. 2016 Dec;10(4):316-323. doi: 10.1097/SPC.0000000000000236.

  PMID: 27661210 BACKGROUND

• Hui D, Hess K, Dibaj SS, Arthur J, Dev R, Dalal S, Reddy S, Bruera E. The minimal clinically important difference of the Richmond Agitation-Sedation Scale in patients with cancer with agitated delirium. Cancer. 2018 May 15;124(10):2246-2252. doi: 10.1002/cncr.31312. Epub 2018 Feb 22.

  PMID: 29469951 BACKGROUND

• Kim J, Shin W. How to do random allocation (randomization). Clin Orthop Surg. 2014 Mar;6(1):103-9. doi: 10.4055/cios.2014.6.1.103. Epub 2014 Feb 14.

  PMID: 24605197 BACKGROUND

• Lawlor PG, Nekolaichuk C, Gagnon B, Mancini IL, Pereira JL, Bruera ED. Clinical utility, factor analysis, and further validation of the memorial delirium assessment scale in patients with advanced cancer: Assessing delirium in advanced cancer. Cancer. 2000 Jun 15;88(12):2859-67.

  PMID: 10870073 BACKGROUND

• Mercadante S, Masedu F, Maltoni M, De Giovanni D, Montanari L, Pittureri C, Berte R, Russo D, Ursini L, Marinangeli F, Aielli F. Symptom expression in advanced cancer patients admitted to hospice or home care with and without delirium. Intern Emerg Med. 2019 Jun;14(4):515-520. doi: 10.1007/s11739-018-1969-9. Epub 2018 Oct 17.

  PMID: 30334235 BACKGROUND

• Morita T, Hirai K, Sakaguchi Y, Tsuneto S, Shima Y. Family-perceived distress from delirium-related symptoms of terminally ill cancer patients. Psychosomatics. 2004 Mar-Apr;45(2):107-13. doi: 10.1176/appi.psy.45.2.107.

  PMID: 15016923 BACKGROUND

• Reston JT, Schoelles KM. In-facility delirium prevention programs as a patient safety strategy: a systematic review. Ann Intern Med. 2013 Mar 5;158(5 Pt 2):375-80. doi: 10.7326/0003-4819-158-5-201303051-00003.

  PMID: 23460093 BACKGROUND

• Sweet L, Adamis D, Meagher DJ, Davis D, Currow DC, Bush SH, Barnes C, Hartwick M, Agar M, Simon J, Breitbart W, MacDonald N, Lawlor PG. Ethical challenges and solutions regarding delirium studies in palliative care. J Pain Symptom Manage. 2014 Aug;48(2):259-71. doi: 10.1016/j.jpainsymman.2013.07.017. Epub 2013 Dec 31.

  PMID: 24388124 BACKGROUND

• Jain R, Arun P, Sidana A, Sachdev A. Comparison of efficacy of haloperidol and olanzapine in the treatment of delirium. Indian J Psychiatry. 2017 Oct-Dec;59(4):451-456. doi: 10.4103/psychiatry.IndianJPsychiatry_59_17.

  PMID: 29497187 RESULT

• Lyu XJ, Kan AD, Chong PH, Lin K, Koh YH, Yeo ZZ. An open-label clinical trial of oral transmucosal haloperidol and oral transmucosal olanzapine in the treatment of terminal delirium at home. Trials. 2022 Apr 14;23(1):311. doi: 10.1186/s13063-022-06238-4.

  PMID: 35422053 DERIVED

MeSH Terms

Conditions

Delirium

Interventions

Olanzapine

Condition Hierarchy (Ancestors)

Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Poh Heng Chong, MD

  HCA Hospice Care

  STUDY DIRECTOR

Central Study Contacts

Xiaojuan Lyu, MD

CONTACT

+65 97303814; xiaojuanl@hcahospicecare.org.sg

Zhi Zheng Yeo, BA

CONTACT

+65 84295323; zhizhengy@hcahospicecare.org.sg

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a prospective, open-label, randomized controlled trial. Patients will be randomly assigned to one of two groups as part of follow-up management.

Study Record Dates

• First Submitted: February 8, 2021
• First Posted: February 11, 2021
• Study Start: September 1, 2021
• Primary Completion: May 1, 2024
• Study Completion: May 1, 2024
• Last Updated: March 1, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)