Advanced Cancer Clinical Trial
Official title:
HALO Trial: Haloperidol vs Olanzapine in Hyperactive Delirium in Palliative Care Patients; A Multi-Centre, Randomised-Controlled Trial
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.
Status | Recruiting |
Enrollment | 72 |
Est. completion date | December 2024 |
Est. primary completion date | December 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 21 Years to 99 Years |
Eligibility | 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 |
Country | Name | City | State |
---|---|---|---|
Singapore | Dover Park Hospice | Singapore | |
Singapore | St. Andrew's Community Hospital | Singapore | |
Singapore | Tan Tock Seng Hospital | Singapore |
Lead Sponsor | Collaborator |
---|---|
Tan Tock Seng Hospital |
Singapore,
Agar 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. Erratum In: JAMA Intern Med. 2017 Feb 1;177(2):293. — View Citation
Boettger 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. — View Citation
Breitbart 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. — View Citation
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. — View Citation
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. — View Citation
Hui 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. — View Citation
Hui 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. — View Citation
Inouye SK. Delirium in older persons. N Engl J Med. 2006 Mar 16;354(11):1157-65. doi: 10.1056/NEJMra052321. No abstract available. Erratum In: N Engl J Med. 2006 Apr 13;354(15):1655. — View Citation
Lin 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.
Skelton 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. — View Citation
Watt 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. — View Citation
Zipser 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. — View Citation
* Note: There are 12 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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. | 8 hours | |
Secondary | 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?" 1) Yes/Sometimes 2) No 3) Not sure/ Unable to answer |
72 hours | |
Secondary | 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 | 72 hours | |
Secondary | Mean Time to control of Hyperactive Delirium | Mean Time to control of Hyperactive Delirium | 72 hours | |
Secondary | Rescue Psychotropic (Mean Doses): Midazolam | Rescue Psychotropic (Mean Doses): Midazolam | 72 hours | |
Secondary | Side-effects of Study Medications | Side-effects of Study Medications | 72 hours | |
Secondary | Survival time in days | Survival time in days | 72 hours | |
Secondary | 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. |
1 hour | |
Secondary | 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. |
72 hours | |
Secondary | 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. |
72 hours | |
Secondary | 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 |
72 hours |
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