HALO Trial: Haloperidol vs Olanzapine in Hyperactive Delirium in Palliative Care Patients; A Multi-Centre, Randomised-Controlled Trial

Summary

1. Background and Clinical Need:

Delirium is common at the end of life and is challenging to control. There is a clinical need to study the benefits of commonly used drugs like Haloperidol and Olanzapine in the management of hyperactive delirium in advanced cancer or end-stage organ disease patients in a scientifically robust manner.
2. Aims/Hypotheses:

The investigators aim to study the effectiveness of Haloperidol compared with Olanzapine in the management of hyperactive delirium in advanced cancer or end-stage organ disease patients receiving palliative care. The investigators hypothesise that Olanzapine is as effective as Haloperidol in the control of hyperactive delirium.
3. Methods:

The investigators will conduct a pragmatic, multi-centre, (hospital, inpatient hospice, community hospital) open-label randomised-controlled trial comparing the use of Haloperidol versus Olanzapine in advanced cancer or end-stage organ disease patients with hyperactive delirium.

The primary outcome is the change in Richmond Agitation and Sedation Scale (RASS) scores among patients in each treatment group at 8 hours post-drug administration.

The secondary outcome is the control of hyperactive delirium at 24, 48 and 72 hours using either Haloperidol or Olanzapine.

The mean doses of Haloperidol and Olanzapine used as well as the volume of rescue Midazolam required as well as side-effects of the study medications, survival after enrolment into study will also be studied.
4. Significance to palliative care The results of this study will advance the knowledge of delirium management worldwide with regards to the efficacy of Haloperidol and Olanzapine in managing hyperactive delirium in patients with advanced cancer or end-stage organ disease.

Haloperidol is used traditionally in palliative care for managing delirium. However, as a conventional anti-psychotic, it does cause extra-pyramidal side-effects. Olanzapine, a newer atypical anti-psychotic with a more favourable side-effect profile is being used increasingly in the control of delirium. These 2 commonly used drugs have never been compared head to head in a randomised-controlled, multi-centre study.

Conditions

• Haloperidol
• Advanced Cancer
• Hyperactive Delirium
• Olanzapine
• End-stage Organ Disease

Interventions

DRUG

Haldol 2mg/ml oral solution

Starting dose: 1mg Maximum Dose within 24 hours: 6mg Doses can be escalated every 2 hourly to the maximum doses allowed within 24 hours. If maximum dose of Haloperidol has been reached for the day (within 24 hours), rescue dose of Midazolam 2mg can be used (2mg Q2H PRN).

DRUG

Olanzapine Actavis 5mg orodispersible tablet

Starting dose: 2.5mg Maximum Dose within 24 hours: 15mg Doses can be escalated every 2 hourly to the maximum doses allowed within 24 hours. If maximum dose of Olanzapine has been reached for the day (within 24 hours), rescue dose of Midazolam 2mg can be used (2mg Q2H PRN).

Sponsors & Collaborators

• Tan Tock Seng Hospital

  lead OTHER

Principal Investigators

• Mervyn Koh · Tan Tock Seng Hospital

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

21 Years

Max Age

99 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-05-18

Primary Completion

2024-12-31

Completion

2024-12-31

Countries

• Singapore

Study Locations