HALO Trial: Haloperidol vs Olanzapine in Hyperactive Delirium in Palliative Care Patients; A Multi-Centre, Randomised-Controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 72
- 试验地点
- 3
- 主要终点
- Change in Richmond Agitation and Sedation Scale (RASS) score
研究概览
简要总结
- 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.
详细描述
(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.
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
- Single (Outcomes Assessor)
盲法说明
The study statistician will be blinded to the treatment allocation and outcome assessments (for example, Richmond Agitation and Sedation Scale).
入排标准
- 年龄范围
- 21 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
- •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
研究组 & 干预措施
Haloperidol Arm
Haldol 2mg/ml oral solution
干预措施: Haldol 2mg/ml oral solution (Drug)
Olanzapine Arm
Olanzapine Actavis 5mg orodispersible tablet
干预措施: Olanzapine Actavis 5mg orodispersible tablet (Drug)
结局指标
主要结局
Change in Richmond Agitation and Sedation Scale (RASS) score
时间窗: 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.
次要结局
- 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.(72 hours)
- Mean dose used of Haloperidol and Olanzapine(72 hours)
- Mean Time to control of Hyperactive Delirium(72 hours)
- Rescue Psychotropic (Mean Doses): Midazolam(72 hours)
- Side-effects of Study Medications(72 hours)
- Survival time in days(72 hours)
- Edmonton Symptom Assessment Score revised (ESAS-r)(1 hour)
- Memorial Delirium Assessment Score (MDAS)(72 hours)
- Richmond Agitation and Sedation Scale (RASS) score(72 hours)
- Caregiver and Nurses Perception on the control of hyperactive delirium(72 hours)
研究者
Mervyn Koh Yong Hwang
Senior Consultant
Tan Tock Seng Hospital