Ignite Creation Date:
2024-05-06 @ 3:47 PM
Last Modification Date:
2024-10-26 @ 1:56 PM
Study NCT ID:
NCT04750395
Status:
RECRUITING
Last Update Posted:
2023-03-01
First Post:
2021-02-08
Brief Title:
Comparing Haloperidol and Olanzapine in Treating Terminal Delirium
Sponsor:
HCA Hospice Care
Organization:
HCA Hospice Care
Study Overview
Official Title:
Open-label Randomized Controlled Trial of Oral Transmucosal Haloperidol and Olanzapine in the Treatment of Terminal Delirium
Status:
RECRUITING
Status Verified Date:
2023-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
HALOLAN
Brief Summary:
As patients with terminal illness enter the dying phase they may experience symptoms of restlessness agitation or cognitive disturbance known as terminal delirium In community care pharmacological therapies are utilized to manage the syndrome the most commonly used being neuroleptics haloperidol and olanzapine
However there is currently a dearth of studies on the efficacy and safety between haloperidol and olanzapine in the community palliative care setting existing studies involve non-terminal patients in the hospital suffering from acute delirium To fill this gap an open-label randomized clinical trial is proposed to compare the effects of haloperidol and olanzapine in the management of terminal delirium in home hospice patients who are imminently dying Key outcome measures are the reduction of delirium symptoms and the reduction of agitation Secondary outcome is comparing the adverse effect burden on patients
However there is currently a dearth of studies on the efficacy and safety between haloperidol and olanzapine in the community palliative care setting existing studies involve non-terminal patients in the hospital suffering from acute delirium To fill this gap an open-label randomized clinical trial is proposed to compare the effects of haloperidol and olanzapine in the management of terminal delirium in home hospice patients who are imminently dying Key outcome measures are the reduction of delirium symptoms and the reduction of agitation Secondary outcome is comparing the adverse effect burden on patients
Detailed Description:
Our study defines terminal delirium as an episode of delirium that occurs during the dying phase usually 72 hours before death Episodes of delirium in the dying phase may be described as terminal restlessness or terminal delirium The use of the label terminal implies a causal relationship between the dying phase and the delirium although the aetiology is often multi-factorial
A prospective open-label randomized controlled trial was designed When a home hospice clinician identifies a patient who meets inclusion criteria their proxy ie family caregivers will be approached by the study team and invited to participate in the study Patients will be randomly assigned to one of two groups as part of follow-up management i Oral Transmucosal Haloperidol or ii Oral Transmucosal Olanzapine
After commencement of the first dose of medication each patient will be observed by their family caregiver and the attending clinician over 72 hours less if the patient dies earlier Time-points for data collection will be at 24 hours 48 hours and 72 hours after first commencement of medication
This study compares two common treatments in clinical practice both of which have demonstrated efficacy greater than placebo Since all participants will receive treatment that is no different from accepted practice a placebo group was deemed unnecessary and unethical thus it was not included
Proxy consent is a method for collecting informed consent where the proxy or person responsible for the potential participant is approached to provide consent on behalf of the prospective participant Proxy consent was suggested as a suitable method for consent collection given the patients absent or fluctuating capacity to consent It was successfully used in dementia and delirium research and was reported to have been acceptable to patients and their caregivers
The clinical staff of the hospice service will be briefed about the study and will assist in recruitment As they provide standard palliative care to the patient the clinical staff will i identify patients who meet inclusion criteria and share preliminary information with caregivers ii confirm the diagnosis of delirium and iii advise caregivers on appropriate non-pharmacological management
The primary caregiver ie proxy will be approached by a study team member who is independent from the management of the patient They will provide more detailed information about the study to the primary caregiver If agreeable the proxy will sign the informed consent form and the dyad is assigned a participant ID number Basic demographic information including patients age sex primary diagnosis and co-morbidities will be collected
Patients may withdraw from the study anytime without compromising further treatment using other drugs or alternative dosage regimen
Randomization sequence is created using Microsoft Excel 2016 with 11 allocation using random block sizes of 2 and 4 As each participant joins they are dispensed either haloperidol or olanzapine according to the generated randomization list
After obtaining consent the participant-caregiver pair will be randomized into either the Haloperidol or Olanzapine group Instructions on how to administer the medication will be provided Caregivers will be advised to serve breakthrough doses of the assigned anti-psychotic drug as needed
A daily pack of medication will be prepared for the caregiver during daily clinical reviews at home The pack will have the correct dosages of medication prepared Subcutaneous SC Midazolam is prepared as rescue medication in the event delirium symptoms remain uncontrolled and distressing after the trial medication are depleted
Per clinical practice the first dose of medication will be given under the supervision of the study team The caregiver will be instructed how to rate the patient using the RASS and will provide the baseline RASS rating The study team will assess the patients baseline symptom severity with the MDAS
Alongside drug therapy usual non-pharmacological interventions will be provided to all patients These interventions include i regularly orientating the patient ii keeping the room bright during the day iii minimizing the use of tubes catheters physical restraints or other immobilizing devices and iv minimizing unnecessary disturbances to the patient
Every six hours caregivers will chart the patients agitation using the RASS Additionally if breakthrough medication is required the time of administration will be documented
To conduct assessments as well as to ensure patients safety the study team will make regular home visits to review the patient 24-hours 48-hours and 72-hours after first dose During each review the study team will document their assessments of patients symptom severity MDAS and observe for adverse events NCI CTCAE The researchers will take appropriate action to ensure patients safety during the trial up to and including recommending the termination of the trial
The trial will be conducted for up to 72 hours after recruitment or until patients death If the patient completes the trial and survives the family will continue to receive support from their primary nurse and attending physician Patients who survive beyond seven days after recruitment will be excluded from per-protocol analysis as they no longer fit the inclusion criteria for the study
The study may be terminated at any point during the trial In that event the caregivers will cease assessment using the RASS while the clinicians will record the reason for cessation and make a final MDAS and NCI CTC assessment where applicable The family will continue to receive support from their primary nurse and attending physician
The proxy may choose to decline from having the patient participate in the trial They may also choose to withdraw the patient from the study at any point during the trial The patient and the family will continue to receive service support from their primary nurse and attending physician thereafter They will advise how persisting symptoms should be managed outside of the study The study team will assure the proxy of this fact before informed consent is collected
SC Midazolam is prepared as rescue medication in the event the symptoms of delirium remain uncontrolled and distressing Rescue medications will be used in any one of the following situations
1 Within 24 hours the total doses for Haloperidol or Olanzapine reach more than 10mg or 20mg respectively and patient remains unsettled ie all prepared medication are finished any time before the next clinical review
2 Patient is unable to tolerate Oral Transmucosal medication
3 Patient experiences serious adverse effects from trial medication
The study will be terminated for that patient in any one of the following situations
1 Rescue medication is used
2 Adverse events related to the trial medication were observed to be intolerable
3 Caregiver asks to withdraw the patient from the study
4 Patient is admitted to hospital
Changes to the severity of delirium are analysed with scores from MDAS Repeated-measures between-factors ANOVA will be employed to analyse differences in MDAS scores over time
If a statistically significant difference is found between medications post-hoc analysis will be conducted to analyse the change in MDAS scores at each time-point
Changes in the patients agitation will be trended using the RASS score The RASS scores from Baseline 6 hours 12 hours and 24 hours will be analysed Moreover an average of the RASS scores for the second day and the third day will be calculated and trended
Secondary outcomes are possible adverse effects due to the medication which is measured using NCI CTCAE For each group the toxicities Akathasia Extrapyramidal disorder and spasticity for each group will be compared
Based on validation studies by Breitbart et al 1997 and Lawlor et al 2000 the mean MDAS scores for patients with delirium is roughly 18 SD 764 Jain et al 2018 reported that using either Haloperidol or Olanzapine led to nearly 55 reduction in patients MDAS score 7-8 points 2 points was estimated to be the minimal important difference between Haloperidol and Olanzapine
Assuming a data collection period of 27 months and a target recruitment size of 80 participants the study must successfully recruit 3 - 4 participants per month
A review of HCA Hospice Cares medical notes from January 2020 to August 2020 found that 250 patients exhibited symptoms of confusion agitation or delirium while in an unstable or deteriorating state approximately 30 patients per month The duration between the date of these case notes and the date of patients death ranged 0 days to 17 days 187 patients died within 7 days Hence an average of 23 potential patients per month would be recruited for the study
A prospective open-label randomized controlled trial was designed When a home hospice clinician identifies a patient who meets inclusion criteria their proxy ie family caregivers will be approached by the study team and invited to participate in the study Patients will be randomly assigned to one of two groups as part of follow-up management i Oral Transmucosal Haloperidol or ii Oral Transmucosal Olanzapine
After commencement of the first dose of medication each patient will be observed by their family caregiver and the attending clinician over 72 hours less if the patient dies earlier Time-points for data collection will be at 24 hours 48 hours and 72 hours after first commencement of medication
This study compares two common treatments in clinical practice both of which have demonstrated efficacy greater than placebo Since all participants will receive treatment that is no different from accepted practice a placebo group was deemed unnecessary and unethical thus it was not included
Proxy consent is a method for collecting informed consent where the proxy or person responsible for the potential participant is approached to provide consent on behalf of the prospective participant Proxy consent was suggested as a suitable method for consent collection given the patients absent or fluctuating capacity to consent It was successfully used in dementia and delirium research and was reported to have been acceptable to patients and their caregivers
The clinical staff of the hospice service will be briefed about the study and will assist in recruitment As they provide standard palliative care to the patient the clinical staff will i identify patients who meet inclusion criteria and share preliminary information with caregivers ii confirm the diagnosis of delirium and iii advise caregivers on appropriate non-pharmacological management
The primary caregiver ie proxy will be approached by a study team member who is independent from the management of the patient They will provide more detailed information about the study to the primary caregiver If agreeable the proxy will sign the informed consent form and the dyad is assigned a participant ID number Basic demographic information including patients age sex primary diagnosis and co-morbidities will be collected
Patients may withdraw from the study anytime without compromising further treatment using other drugs or alternative dosage regimen
Randomization sequence is created using Microsoft Excel 2016 with 11 allocation using random block sizes of 2 and 4 As each participant joins they are dispensed either haloperidol or olanzapine according to the generated randomization list
After obtaining consent the participant-caregiver pair will be randomized into either the Haloperidol or Olanzapine group Instructions on how to administer the medication will be provided Caregivers will be advised to serve breakthrough doses of the assigned anti-psychotic drug as needed
A daily pack of medication will be prepared for the caregiver during daily clinical reviews at home The pack will have the correct dosages of medication prepared Subcutaneous SC Midazolam is prepared as rescue medication in the event delirium symptoms remain uncontrolled and distressing after the trial medication are depleted
Per clinical practice the first dose of medication will be given under the supervision of the study team The caregiver will be instructed how to rate the patient using the RASS and will provide the baseline RASS rating The study team will assess the patients baseline symptom severity with the MDAS
Alongside drug therapy usual non-pharmacological interventions will be provided to all patients These interventions include i regularly orientating the patient ii keeping the room bright during the day iii minimizing the use of tubes catheters physical restraints or other immobilizing devices and iv minimizing unnecessary disturbances to the patient
Every six hours caregivers will chart the patients agitation using the RASS Additionally if breakthrough medication is required the time of administration will be documented
To conduct assessments as well as to ensure patients safety the study team will make regular home visits to review the patient 24-hours 48-hours and 72-hours after first dose During each review the study team will document their assessments of patients symptom severity MDAS and observe for adverse events NCI CTCAE The researchers will take appropriate action to ensure patients safety during the trial up to and including recommending the termination of the trial
The trial will be conducted for up to 72 hours after recruitment or until patients death If the patient completes the trial and survives the family will continue to receive support from their primary nurse and attending physician Patients who survive beyond seven days after recruitment will be excluded from per-protocol analysis as they no longer fit the inclusion criteria for the study
The study may be terminated at any point during the trial In that event the caregivers will cease assessment using the RASS while the clinicians will record the reason for cessation and make a final MDAS and NCI CTC assessment where applicable The family will continue to receive support from their primary nurse and attending physician
The proxy may choose to decline from having the patient participate in the trial They may also choose to withdraw the patient from the study at any point during the trial The patient and the family will continue to receive service support from their primary nurse and attending physician thereafter They will advise how persisting symptoms should be managed outside of the study The study team will assure the proxy of this fact before informed consent is collected
SC Midazolam is prepared as rescue medication in the event the symptoms of delirium remain uncontrolled and distressing Rescue medications will be used in any one of the following situations
1 Within 24 hours the total doses for Haloperidol or Olanzapine reach more than 10mg or 20mg respectively and patient remains unsettled ie all prepared medication are finished any time before the next clinical review
2 Patient is unable to tolerate Oral Transmucosal medication
3 Patient experiences serious adverse effects from trial medication
The study will be terminated for that patient in any one of the following situations
1 Rescue medication is used
2 Adverse events related to the trial medication were observed to be intolerable
3 Caregiver asks to withdraw the patient from the study
4 Patient is admitted to hospital
Changes to the severity of delirium are analysed with scores from MDAS Repeated-measures between-factors ANOVA will be employed to analyse differences in MDAS scores over time
If a statistically significant difference is found between medications post-hoc analysis will be conducted to analyse the change in MDAS scores at each time-point
Changes in the patients agitation will be trended using the RASS score The RASS scores from Baseline 6 hours 12 hours and 24 hours will be analysed Moreover an average of the RASS scores for the second day and the third day will be calculated and trended
Secondary outcomes are possible adverse effects due to the medication which is measured using NCI CTCAE For each group the toxicities Akathasia Extrapyramidal disorder and spasticity for each group will be compared
Based on validation studies by Breitbart et al 1997 and Lawlor et al 2000 the mean MDAS scores for patients with delirium is roughly 18 SD 764 Jain et al 2018 reported that using either Haloperidol or Olanzapine led to nearly 55 reduction in patients MDAS score 7-8 points 2 points was estimated to be the minimal important difference between Haloperidol and Olanzapine
Assuming a data collection period of 27 months and a target recruitment size of 80 participants the study must successfully recruit 3 - 4 participants per month
A review of HCA Hospice Cares medical notes from January 2020 to August 2020 found that 250 patients exhibited symptoms of confusion agitation or delirium while in an unstable or deteriorating state approximately 30 patients per month The duration between the date of these case notes and the date of patients death ranged 0 days to 17 days 187 patients died within 7 days Hence an average of 23 potential patients per month would be recruited for the study
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None