Open-label Randomized Controlled Trial of Oral Transmucosal Haloperidol and Olanzapine in the Treatment of Terminal Delirium
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Severity of terminal delirium, measured by the Richmond Agitation-Sedation Scale modified for palliative care (RASS-PAL)
研究概览
简要总结
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.
详细描述
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 (i.e. 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 patient's 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 21 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient is above 21 years of age.
- •Patient was diagnosed with a terminal illness and is receiving end-of-life care at home.
- •Patient is assessed to be acutely dying (estimated prognosis of three days or less).
- •Patient is diagnosed with delirium, as described in the DSM-V (American Psychiatric Association, 2013)
排除标准
- •Patient does not have a caregiver at home.
- •Patient has a prior history of dementia, psychosis, schizophrenia or any other mental health issue followed up by psychiatrists or other specialists.
- •Patient is currently receiving, or has been administered Haloperidol or Olanzapine less than a week before participating in the study.
- •Patient has known allergies or adverse reactions to Haloperidol or Olanzapine.
- •Patients who survive 7 days after recruitment will be excluded from the study.
研究组 & 干预措施
Haloperidol
Every 24 hours, patients will receive two regular doses of OT Haloperidol 2.5mg. Patients may also receive up to two breakthrough doses within a minimum interval of one hour from the last dose. In total, up to four doses of medication will be prepared.
干预措施: Haloperidol Solution (Drug)
Olanzapine
Every 24 hours, patients will receive two regular doses of OT Olanzapine 5.0mg. Patients may also receive up to two breakthrough doses within a minimum interval of one hour from the last dose. In total, up to four doses of medication will be prepared.
干预措施: Olanzapine Tablets (Drug)
结局指标
主要结局
Severity of terminal delirium, measured by the Richmond Agitation-Sedation Scale modified for palliative care (RASS-PAL)
时间窗: 72 hours
The RASS is a simple observational instrument assessing levels of sedation and agitation. It requires no patient input and ranges from +4 (overly combative) to -5 (unarousable). It is considered less time-consuming and easier to use than other similar instruments. Developed for adult intensive care unit patients, the scale demonstrated strong inter-rater reliability in that setting. A modified version was de-signed for use in the palliative care setting, which produced acceptable psychometric properties. Hui et. al. (2018) had caregivers using the RASS to assess patients, which gave ratings similar to clinicians.
Severity of agitation, measured by the Memorial Delirium Assessment Scale (MDAS)
时间窗: 72 hours
MDAS is a ten-item, four-point clinician-rated scale designed to quantify the severity of delirium in medically-ill patients (range 1 - 40). Items included in the scale reflect the diagnostic criteria for delirium in the DSM-IV. It has very good psychometric proper-ties, with high reliability (r = .91) and good Discriminant and Concurrent validity. Though the scale was intended to assess patients based on all ten items, it was suggested that items in MDAS can be pro-rated in the event the patient is not able to communicate. The higher the score, the more severe the agitation.
次要结局
- Adverse effects or toxicity, measured by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)(0-72 hours)