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

• Status: Not yet recruiting
• Trial end date: 2022-10-01
• Target enrollment: 0
• Participant gender: All

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 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 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 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.

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Tan Tock Seng Hospital
• Treatments: Olanzapine

Criteria

Inclusion Criteria:

1. Patients with advanced cancer

2. Age ≥ 21 years old

3. Fulfil All Three Diagnosis of Delirium:

• Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) criteria for delirium

• Memorial Delirium Assessment Scale (MDAS)©1996 > 13

• Richmond Agitation-Sedation Scale (RASS) Score +1 to +3

4. Able to consume medications orally

5. Prognosis > 48 hrs (Clinician Estimate)

Exclusion Criteria:

1. Parkinson's Disease or Vascular Parkinsonism

2. Dementia with BPSD and active behavioral issues

3. Chronic Schizophrenia on regular Anti-psychotic medications

4. Taking any regular Benzodiazepines* or any Anti-psychotic** medications

5. Known allergy to Haloperidol or Olanzapine

6. History of Substance Abuse

7. Known Prolonged corrected QT interval (QTc) Syndrome (In Patient's Medical History)

8. Prognosis < 48 hours (Clinician's Estimate)

9. Unable to consume oral medications

10. Richmond Agitation and Sedation Scale (RASS) Score +4 (Too agitated and will require Parenteral Anti-psychotics and/or Benzodiazepines) * e.g. Lorazepam, Alprazolam, Clonazepam, Midazolam **e.g. Haloperidol, Risperidone, Quetiapine, Olanzapine