HaloperidolPhase 3NCT04833023
HALO Trial: Haloperidol vs Olanzapine in Hyperactive Delirium in Palliative Care Patients; A Multi-Centre, Randomised-Controlled Trial
A Phase 3 study testing Haldol 2mg/ml oral solution and Olanzapine Actavis 5mg orodispersible tablet in people with Haloperidol and Advanced Cancer, run by Tan Tock Seng Hospital at 3 sites in Singapore.
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… Read more about this study
- Who is it for?
- Ages 21 to 99 years
- Conditions the study is for
- Haloperidol, Advanced Cancer, Hyperactive Delirium
- What is being tested?
- Haldol 2mg/ml oral solution and Olanzapine Actavis 5mg orodispersible tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 3 sitesSingapore
- Study dates
- 18 May 2022to 25 Sep 2025
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with advanced cancer or end-stage organ disease
- Age ≥ 21 years old
- 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
- Able to consume medications orally
- Prognosis > 48 hrs (Clinician Estimate)
Who cannot join
- Parkinson's Disease or Vascular Parkinsonism
- Patient with dementia
- Chronic Schizophrenia on regular Anti-psychotic medications
- Taking any regular Benzodiazepines* or any Anti-psychotic** medications
- Known allergy to Haloperidol or Olanzapine
- History of Substance Abuse
Show all 11Show fewer
- Known Prolonged corrected QT interval (QTc) Syndrome (In Patient's Medical History)
- Prognosis < 48 hours (Clinician's Estimate)
- Unable to consume oral medications
- Richmond Agitation and Sedation Scale (RASS) Score +4 (Too agitated and will require Parenteral Anti-psychotics and/or Benzodiazepines)
- Pregnancy * e.g. Lorazepam, Alprazolam, Clonazepam, Midazolam **e.g. Haloperidol, Risperidone, Quetiapine, Olanzapine
Trial locations and contacts
3 sites in 1 country.
Singapore3 sites
Tan Tock Seng Hospital
Singapore, Singapore, 308433
Dover Park Hospice
Singapore, 308436
St. Andrew's Community Hospital
Singapore, 529895
About this study
- 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.
- 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.
- 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.
- 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.
Read the detailed description
(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 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 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 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.
- Being tested
- Haldol 2mg/ml oral solution, Olanzapine Actavis 5mg orodispersible tablet
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Haldol 2mg/ml oral solutionDrug
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).
Olanzapine Actavis 5mg orodispersible tabletDrug
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).
| Study group | Role | What they receive |
|---|---|---|
| Haloperidol Arm | Active comparator | Haldol 2mg/ml oral solution Receives: Drug: Haldol 2mg/ml oral solution |
| Olanzapine Arm | Active comparator | Olanzapine Actavis 5mg orodispersible tablet Receives: Drug: Olanzapine Actavis 5mg orodispersible tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Richmond Agitation and Sedation Scale (RASS) score
The change in Richmond Agitation and Sedation Scale (RASS) score 8 hours after administration of either Haloperidol and Olanzapine. Minimum value is -5 which represents that the patient is in hypoactive delirium and is unarousable and maximum value is +4 with the higher score representing that the patient is in hyperactive delirium and is combative. The aim of the study is to reduce the hyperactive delirium to a score of 0 which represents patient is alert and calm.
Measured: 8 hours
Secondary outcomes (10)
Comparing Patient and Family's concurrence on state of delirium with of the Diagnosis of Delirium from Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) criteria for delirium.
There have not been any studies that looked at interviewing patients who are delirious about their acknowledgement and concurrence of their state of delirium. The investigators aim to interview patients by asking the patient 'Did you feel confused' and caregivers similarly by asking 'Do you feel that your loved one is Confused' as shown as an example below and compare this to the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) criteria for delirium.
Please ask the Patient the following question "Do you feel that you are confused?"
- Yes/Sometimes
- No
- Not Sure/ Unable to answer Please ask the Family member or Caregiver the following question "Do you think the patient is confused?"
- Yes/Sometimes 2) No 3) Not sure/ Unable to answer
Measured: 72 hours
Mean dose used of Haloperidol and Olanzapine
Mean doses of Haloperidol and Olanzapine used at 8hours / D1 / D2 / D3 from the first time-point that the study medication is administered to the patients
Measured: 72 hours
Mean Time to control of Hyperactive Delirium
Mean Time to control of Hyperactive Delirium
Measured: 72 hours
Rescue Psychotropic (Mean Doses): Midazolam
Rescue Psychotropic (Mean Doses): Midazolam
Measured: 72 hours
Side-effects of Study Medications
Side-effects of Study Medications
Measured: 72 hours
Survival time in days
Survival time in days
Measured: 72 hours
Edmonton Symptom Assessment Score revised (ESAS-r)
Edmonton Symptom Assessment Score revised (ESAS-r) - At the point of recruitment
Minimum value for the scale is 0 and maximum value for the scale is 10 with the higher value representing worse outcome.
Measured: 1 hour
Memorial Delirium Assessment Score (MDAS)
Memorial Delirium Assessment Score (MDAS) - At the point of recruitment and after 72 hours
It is a scale comprising of 10 items with scores of 0-3 for each question. Add up the score for all 10 questions and scores with more than or equal to 13 point indicates delirium.
Measured: 72 hours
Richmond Agitation and Sedation Scale (RASS) score
Richmond Agitation and Sedation Scale (RASS) score: 8hours / 24hours (Day 1) / 48 hours (Day 2) / 72 hours (Day 3)
Minimum value is -5 which represents that the patient is in hypoactive delirium and is unarousable and maximum value is +4 with the higher score representing that the patient is in hyperactive delirium and is combative. The aim of the study is to reduce the hyperactive delirium to a score of 0 which represents patient is alert and calm.
Measured: 72 hours
Caregiver and Nurses Perception on the control of hyperactive delirium
Caregiver and Nurses Perception on the control of hyperactive delirium (5-point Likert Scale). Kindly refer to the example of the question below.
The patient is less agitated as compared to 72 hours ago? (Clinician/Nurse):
- - Strongly Disagree
- - Disagree
- - Neutral
- - Agree
- - Strongly Agree
The patient is less agitated as compared to 72 hours ago? (Family/Caregiver):
- - Strongly Disagree
- - Disagree
- - Neutral
- - Agree
- - Strongly Agree
Measured: 72 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2021
- Study start18 May 2022
- Primary completion25 Sep 2025
- Study completion25 Sep 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for HaloperidolStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tan Tock Seng Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mervyn Koh Yong Hwang, Tan Tock Seng Hospital
- Investigators
- Mervyn Koh, Principal investigator, Tan Tock Seng Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04833023
- Sponsor's protocol ID
- PalC-RG-20/P001
- Status last verified
- Sep 2026
- First submitted
- 30 Mar 2021
- Last updated
- 5 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: There are no plans to make individual participant data available to other researchers.
Publications
Hosie A, Davidson PM, Agar M, Sanderson CR, Phillips J. Delirium prevalence, incidence, and implications for screening in specialist palliative care inpatient settings: a systematic review. Palliat Med. 2013 Jun;27(6):486-98. doi: 10.1177/0269216312457214. Epub 2012 Sep 17.
PubMed 22988044Watt CL, Momoli F, Ansari MT, Sikora L, Bush SH, Hosie A, Kabir M, Rosenberg E, Kanji S, Lawlor PG. The incidence and prevalence of delirium across palliative care settings: A systematic review. Palliat Med. 2019 Sep;33(8):865-877. doi: 10.1177/0269216319854944. Epub 2019 Jun 11.
PubMed 31184538Hui D. Delirium in the palliative care setting: "Sorting" out the confusion. Palliat Med. 2019 Sep;33(8):863-864. doi: 10.1177/0269216319861896. No abstract available.
PubMed 31395002Inouye SK. Delirium in older persons. N Engl J Med. 2006 Mar 16;354(11):1157-65. doi: 10.1056/NEJMra052321. No abstract available.
PubMed 16540616Skelton L, Guo P. Evaluating the effects of the pharmacological and nonpharmacological interventions to manage delirium symptoms in palliative care patients: systematic review. Curr Opin Support Palliat Care. 2019 Dec;13(4):384-391. doi: 10.1097/SPC.0000000000000458.
PubMed 31490322Zipser CM, Knoepfel S, Hayoz P, Schubert M, Ernst J, von Kanel R, Boettger S. Clinical management of delirium: The response depends on the subtypes. An observational cohort study in 602 patients. Palliat Support Care. 2020 Feb;18(1):4-11. doi: 10.1017/S1478951519000609.
PubMed 31506133Hui D, Frisbee-Hume S, Wilson A, Dibaj SS, Nguyen T, De La Cruz M, Walker P, Zhukovsky DS, Delgado-Guay M, Vidal M, Epner D, Reddy A, Tanco K, Williams J, Hall S, Liu D, Hess K, Amin S, Breitbart W, Bruera E. Effect of Lorazepam With Haloperidol vs Haloperidol Alone on Agitated Delirium in Patients With Advanced Cancer Receiving Palliative Care: A Randomized Clinical Trial. JAMA. 2017 Sep 19;318(11):1047-1056. doi: 10.1001/jama.2017.11468.
PubMed 28975307Breitbart W, Alici Y. Agitation and delirium at the end of life: "We couldn't manage him". JAMA. 2008 Dec 24;300(24):2898-910, E1. doi: 10.1001/jama.2008.885.
PubMed 19109118Agar MR, Lawlor PG, Quinn S, Draper B, Caplan GA, Rowett D, Sanderson C, Hardy J, Le B, Eckermann S, McCaffrey N, Devilee L, Fazekas B, Hill M, Currow DC. Efficacy of Oral Risperidone, Haloperidol, or Placebo for Symptoms of Delirium Among Patients in Palliative Care: A Randomized Clinical Trial. JAMA Intern Med. 2017 Jan 1;177(1):34-42. doi: 10.1001/jamainternmed.2016.7491.
PubMed 27918778Boettger S, Friedlander M, Breitbart W, Passik S. Aripiprazole and haloperidol in the treatment of delirium. Aust N Z J Psychiatry. 2011 Jun;45(6):477-82. doi: 10.3109/00048674.2011.543411.
PubMed 21563866Lin CJ, Sun FJ, Fang CK. An open trial comparing haloperidol with olanzapine for the treatment of delirium in palliative and hospice center cancer patients. J Internal Med Taiwan 2008; 19:346-354.
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.
PubMed 24684942
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- HALO Trial: Haloperidol vs Olanzapine in Hyperactive Delirium in Palliative Care Patients; A Multi-Centre, Randomised-Controlled Trial
- ClinicalTrials.gov ID
- NCT04833023
- Acronym / sponsor ID
- PalC-RG-20/P001
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Tan Tock Seng HospitalUniversity, hospital or other
- Study start
- 18 May 2022 (actual)
- Primary completion
- 25 Sep 2025 (actual)
- Study completion
- 25 Sep 2025 (actual)
- First posted
- 6 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
- 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.
- 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.
- 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.
- 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.
Detailed description
(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 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 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 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Haloperidol Arm | Active comparator | Drug: Haldol 2mg/ml oral solutionHaldol 2mg/ml oral solution |
| Olanzapine Arm | Active comparator | Drug: Olanzapine Actavis 5mg orodispersible tabletOlanzapine Actavis 5mg orodispersible tablet |
Who may qualify
- Ages
- 21 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients with advanced cancer or end-stage organ disease
- Age ≥ 21 years old
- Fulfil All Three Diagnosis of Delirium:
- Able to consume medications orally
- Prognosis > 48 hrs (Clinician Estimate)
Key exclusion criteria (11 listed)
- Parkinson's Disease or Vascular Parkinsonism
- Patient with dementia
- Chronic Schizophrenia on regular Anti-psychotic medications
- Taking any regular Benzodiazepines* or any Anti-psychotic** medications
- Known allergy to Haloperidol or Olanzapine
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Haldol 2mg/ml oral solutionStarting 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 | Haloperidol Arm |
| Olanzapine Actavis 5mg orodispersible tabletStarting 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). | Drug | Olanzapine Arm |
Primary outcome
Change in Richmond Agitation and Sedation Scale (RASS) score
Time frame: 8 hours
The change in Richmond Agitation and Sedation Scale (RASS) score 8 hours after administration of either Haloperidol and Olanzapine. Minimum value is -5 which represents that the patient is in hypoactive delirium and is unarousable and maximum value is +4 with the higher score representing that the patient is in hyperactive delirium and is combative. The aim of the study is to reduce the hyperactive delirium to a score of 0 which represents patient is alert and calm.
10 secondary outcomes
Comparing Patient and Family's concurrence on state of delirium with of the Diagnosis of Delirium from Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) criteria for delirium.
Time frame: 72 hours
Mean dose used of Haloperidol and Olanzapine
Time frame: 72 hours
Mean Time to control of Hyperactive Delirium
Time frame: 72 hours
Rescue Psychotropic (Mean Doses): Midazolam
Time frame: 72 hours
Side-effects of Study Medications
Time frame: 72 hours
Survival time in days
Time frame: 72 hours
Edmonton Symptom Assessment Score revised (ESAS-r)
Time frame: 1 hour
Memorial Delirium Assessment Score (MDAS)
Time frame: 72 hours
Richmond Agitation and Sedation Scale (RASS) score
Time frame: 72 hours
Caregiver and Nurses Perception on the control of hyperactive delirium
Time frame: 72 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2026.
- Background: PubMed 22988044Hosie A, Davidson PM, Agar M, Sanderson CR, Phillips J. Delirium prevalence, incidence, and implications for screening in specialist palliative care inpatient settings: a systematic review. Palliat Med. 2013 Jun;27(6):486-98. doi: 10.1177/0269216312457214. Epub 2012 Sep 17.
- Background: PubMed 31184538Watt CL, Momoli F, Ansari MT, Sikora L, Bush SH, Hosie A, Kabir M, Rosenberg E, Kanji S, Lawlor PG. The incidence and prevalence of delirium across palliative care settings: A systematic review. Palliat Med. 2019 Sep;33(8):865-877. doi: 10.1177/0269216319854944. Epub 2019 Jun 11.
- Background: PubMed 31395002Hui D. Delirium in the palliative care setting: "Sorting" out the confusion. Palliat Med. 2019 Sep;33(8):863-864. doi: 10.1177/0269216319861896. No abstract available.
- Background: PubMed 16540616Inouye SK. Delirium in older persons. N Engl J Med. 2006 Mar 16;354(11):1157-65. doi: 10.1056/NEJMra052321. No abstract available.
- Background: PubMed 31490322Skelton L, Guo P. Evaluating the effects of the pharmacological and nonpharmacological interventions to manage delirium symptoms in palliative care patients: systematic review. Curr Opin Support Palliat Care. 2019 Dec;13(4):384-391. doi: 10.1097/SPC.0000000000000458.
- Background: PubMed 31506133Zipser CM, Knoepfel S, Hayoz P, Schubert M, Ernst J, von Kanel R, Boettger S. Clinical management of delirium: The response depends on the subtypes. An observational cohort study in 602 patients. Palliat Support Care. 2020 Feb;18(1):4-11. doi: 10.1017/S1478951519000609.
- Background: PubMed 28975307Hui D, Frisbee-Hume S, Wilson A, Dibaj SS, Nguyen T, De La Cruz M, Walker P, Zhukovsky DS, Delgado-Guay M, Vidal M, Epner D, Reddy A, Tanco K, Williams J, Hall S, Liu D, Hess K, Amin S, Breitbart W, Bruera E. Effect of Lorazepam With Haloperidol vs Haloperidol Alone on Agitated Delirium in Patients With Advanced Cancer Receiving Palliative Care: A Randomized Clinical Trial. JAMA. 2017 Sep 19;318(11):1047-1056. doi: 10.1001/jama.2017.11468.
- Background: PubMed 19109118Breitbart W, Alici Y. Agitation and delirium at the end of life: "We couldn't manage him". JAMA. 2008 Dec 24;300(24):2898-910, E1. doi: 10.1001/jama.2008.885.
- Background: PubMed 27918778Agar MR, Lawlor PG, Quinn S, Draper B, Caplan GA, Rowett D, Sanderson C, Hardy J, Le B, Eckermann S, McCaffrey N, Devilee L, Fazekas B, Hill M, Currow DC. Efficacy of Oral Risperidone, Haloperidol, or Placebo for Symptoms of Delirium Among Patients in Palliative Care: A Randomized Clinical Trial. JAMA Intern Med. 2017 Jan 1;177(1):34-42. doi: 10.1001/jamainternmed.2016.7491.
- Background: PubMed 21563866Boettger S, Friedlander M, Breitbart W, Passik S. Aripiprazole and haloperidol in the treatment of delirium. Aust N Z J Psychiatry. 2011 Jun;45(6):477-82. doi: 10.3109/00048674.2011.543411.
- BackgroundLin CJ, Sun FJ, Fang CK. An open trial comparing haloperidol with olanzapine for the treatment of delirium in palliative and hospice center cancer patients. J Internal Med Taiwan 2008; 19:346-354.
- Background: PubMed 24684942Bush 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.
- Individual participant dataSharing planned: No. There are no plans to make individual participant data available to other researchers.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mervyn Koh principal investigator
Tan Tock Seng Hospital
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Haldol 2mg/ml oral solution and Olanzapine Actavis 5mg orodispersible tablet in people with Haloperidol and Advanced Cancer, run by Tan Tock Seng Hospital at 3 sites in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Richmond Agitation and Sedation Scale (RASS) score (time frame: 8 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04833023, which also lists 12 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2026.