Clinical Trial Finder

Inclusion Criteria:

1. Patients with advanced cancer or end-stage organ disease. 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. Patient with dementia. 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) 11. Pregnancy * e.g. Lorazepam, Alprazolam, Clonazepam, Midazolam **e.g. Haloperidol, Risperidone, Quetiapine, Olanzapine

(A) Background & Clinical Need.Delirium is commonly encountered in palliative care with a prevalence of between 26-74% and rising to as high as 88% nearer the end of life (2). It negatively impacts patient care and leads to greater morbidity and mortality (3). There are 3 sub-types of delirium

• - hyperactive, mixed and hypoactive (4) with majority of well-designed studies in palliative care focusing on the management of delirium as a whole (5).

However, recently published literature suggests that these delirium subtypes appear to have different trajectories and are also generally treated differently (6). Overall, the management of delirium in palliative care remains controversial. Agar had shown in a randomised controlled trial that supportive care may be superior to the use of anti-psychotics, even though the patients in Agar's study were only 'mildly' delirious and the overall doses of anti-psychotics used was lower than compared to common practice (9). Other studies have shown the benefits of anti-psychotics like haloperidol, olanzapine and aripiprazole in the management of delirium (10,11). Hui et al was the only study which looked at the management of hyperactive delirium in the palliative care setting (7). Patients with hyperactive delirium exhibit restlessness, agitation and even aggression towards their loved ones and to healthcare providers caring for them (8). To date, there have not been any multi-centre, randomised-controlled trial which has addressed the effectiveness of oral Haloperidol vs.#46;Olanzapine in the management of hyperactive delirium in the palliative care setting. (B) Specific Aims.The investigators aim to study the effectiveness of Olanzapine vs.#46;Haloperidol in the management of hyperactive delirium in patients with advanced cancer or end-stage organ disease in 3 different settings. The primary outcome is the change in Richmond Agitation and Sedation Scale (RASS) scores among patients in each treatment group at 8 hours after the administration of Haloperidol or Olanzapine as measured using the Richmond Agitation and Sedation Scale (RASS). The secondary outcome is the change in Richmond Agitation and Sedation Scale (RASS) score at 24, 48 and 72 hours with the use of either Haloperidol or Olanzapine required. The mean doses of Haloperidol and Olanzapine used as well as the doses of rescue Midazolam required as well as side-effects of the study medications, survival after enrolment into study will also be studied. (C) Methods.Study Design.The investigators aim to conduct a multi-centre, randomised-controlled, open-label trial (Acute Hospital Palliative Care Unit, Palliative Care Unit in Community Hospital and Inpatient Hospice) comparing the use of haloperidol vs.#46;olanzapine in a 1:1 ratio in advanced cancer or end-stage organ disease patients with hyperactive delirium. Patients will be followed up for 3 days (72 hours) with regards to the response to study medications as well as other factors and outcomes as described below. Mortality data will also be collected. The study will be conducted in 3 different Palliative Care Centres in Singapore

• - 1.

Tan Tock Seng Hospital Acute Palliative Care Unit, 2. Palliative Care Unit in St Andrews' Community Hospital and 3. Dover Park Hospice. This is to increase the pragmatic applicability and external validity in this study to different palliative care units in Singapore and internationally. Informed consent will be taken from the patient's legal representative according to the HBR Act as the patients recruited will be delirious and therefore will not able to provide informed consent adequately.

Arms

Active Comparator: Haloperidol Arm

Haldol 2mg/ml oral solution

Active Comparator: Olanzapine Arm

Olanzapine Actavis 5mg orodispersible tablet

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).