Delirium is the most common and distressing neuropsychiatric syndrome in cancer patients. It has a negative effect on symptom assessment, patient-clinician communication, decision making, and survival. Agitated delirium can be particularly distressing to patients and caregivers. Lorazepam may have a role as adjuvant therapy in the management of agitated delirium. Specifically, it may provide more rapid control of agitation and anxiety, thus decreasing delirium-related distress in patients, caregivers, and healthcare professionals. Furthermore, lorazepam may reduce delirium recall through its amnesic effect. Few clinical trials of delirium have been conducted in the palliative care setting; such trials are urgently needed to improve the quality of life of cancer patients with this devastating syndrome. The proposed study is a high-impact, double-blind, randomized, placebo-controlled study to determine lorazepam's effectiveness, when given as adjuvant therapy to haloperidol, in the treatment of agitated delirium in cancer patients. The primary aim of this study is to assess the within-arm effect of single-dose lorazepam or placebo on agitation intensity (Richmond Agitation Sedation Scale [RASS]) over 8 hours among patients admitted to an acute palliative care unit (APCU); the secondary aims are to obtain preliminary estimates of single-dose lorazepam's within-arm effects, when given as an adjuvant agent to haloperidol, on (1) the proportion of patients with target RASS -2 to +1, (2) delirium-related distress in nurses and caregivers, (3) symptom expression, (4) delirium severity, (5) need for neuroleptics, (6) delirium recall in patients, (7) adverse effects, (8) discharge outcomes, and (9) survival in cancer patients, and to obtain preliminary estimates of the between-arm effect size between single-dose lorazepam and placebo on RASS over 8 hours. After obtaining surrogate consent, we will administer a single dose of lorazepam or placebo, in addition to haloperidol for agitation. Participants will be observed closely over the first 8 hours; follow-up assessments will be completed daily until discharge. This study is highly innovative because of the (1) never-before-tested indication of lorazepam as adjuvant therapy for refractory delirium, (2) the unique study population (i.e., advanced cancer patients and caregivers), (3) the distinctive study setting (i.e. the APCU), and (4) the novel outcome measures (i.e., delirium-related distress and delirium recall). Successful completion of this proof-of-concept study will pave the way for a large randomized controlled trial that is adequately powered to determine the effect of lorazepam on agitated delirium. This study is expected to have a positive effect by offering new evidence-based therapeutic options for palliating agitated delirium beyond single-agent haloperidol, thus enhancing our understanding of lorazepam's effects on clinically important delirium outcomes, shifting paradigms in end-of-life care and research, and ultimately, improving the quality of life of patients with advanced cancer and their caregivers.
The goal of this study is to assess the effect of lorazepam and placebo, when given as adjuvant therapy with haloperidol, at reducing agitation in advanced cancer patients with refractory delirium. We will also determine the effects of lorazepam and a placebo on the level of agitation, need for neuroleptics, delirium-related distress in nurses and caregivers, delirium recall, symptom expression, adverse effects, delirium severity, discharge outcomes, and survival. We expect that adjuvant lorazepam will facilitate a clinically relevant improvement in agitation, delirium-related distress, delirium recall, and delirium severity in cancer patients.
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