None listed
Conditions
Brief summary
Anxiety is common in adults with advanced life-limiting disease, adversely affecting quality of life, social relationships and daily functioning at a critical time. This current study will assess the feasibility of a larger multi-centre, randomised, double-blind, placebo-controlled Phase III trial of oral lorazepam for symptoms of anxiety in participants with advanced life-limiting disease. Who is it for? You may be eligible to join this study if you are aged 18 and above with advanced life-limiting disease receiving specialist palliative care input and experiencing symptoms of anxiety and meet all the inclusion and none of the exclusion criteria. Study details Participants in this study are randomly allocated (by chance) to one of two groups. Arm 1 will be lorazepam and Arm 2 will be placebo. The study treatment will be commenced at a dose of 0.5mg (1 capsule) at night. If this is tolerated at Day 3, the dose will be increased to 0.5mg twice daily. A dose titration schedule with up to weekly dose review will then be followed. Each week the total daily dose may be increased by 0.5mg based on clinical assessment, adverse events assessment and HADS-A score, up to a maximum dose of 2mg twice daily (4 capsules twice daily). The study treatment will be continued for 12 weeks, unless criteria for discontinuation of treatment are met prior to this.
Interventions
The treatment with study drug - lorazepam will commence on Day 1, Week 1 and continue for up to 12 weeks.
On Days 1 and 2 lorazepam will be taken as 1 capsule (0.5 mg) at night only.
On Day 3 dose toxicity will be reviewed and if no toxicities occurred, the dose will be increased by 1 capsule (0.5 mg) and taken twice daily (in the morning and in the evening) starting from the following morning on Day 4.
At the end of each week (1, 2, 3, 4 etc.) dose toxicity will be assessed and if no toxicitie
The treatment with study drug - lorazepam will commence on Day 1, Week 1 and continue for up to 12 weeks. On Days 1 and 2 lorazepam will be taken as 1 capsule (0.5 mg) at night only. On Day 3 dose toxicity will be reviewed and if no toxicities occurred, the dose will be increased by 1 capsule (0.5 mg) and taken twice daily (in the morning and in the evening) starting from the following morning on Day 4. At the end of each week (1, 2, 3, 4 etc.) dose toxicity will be assessed and if no toxicities occurred, dose will be increased by 0.5 mg for the following week until dose maximum titration is reached (2mg twice a day). If the dose is not tolerated, the daily dose will be reduced by 1 capsule (0.5 mg). Sites must maintain an accurate record of dispensing and returns of each study drug for each trial participant. Participants will be instructed to keep all study drug bottles (empty or otherwise). Following each face-to-face assessment visit, these should be returned to the site pharmacy for accountability, using the established practice within the site/hospital.
Sponsors
Peter MacCallum Cancer Centre
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Provide written informed consent. Age greater than or equal to 18 years. Inpatient or outpatient receiving specialist palliative care input. Advanced cancer (histological or clinical diagnosis) defined by intent of treatment no longer being curative or diagnosis of non-malignant advanced life-limiting illness. Persistent or recurrent anxiety causing clinically significant distress or functional impairment, as determined by the Investigator through clinical interview as part of the medical assessment. Able to tolerate oral medication. Able to read and understand sufficient English to complete all required study questionnaires. Capable of completing assessments and complying with the study procedures.
Exclusion criteria
Psychiatric disorder other than anxiety or depression, unless stable for the past 3 months as assessed by the Investigator. Untreated depression, severe depression or suicidality as determined by the Investigator through clinical interview. Current or recent history of alcohol abuse or substance misuse. Formal diagnosis of severe respiratory failure (type 1 or 2). Formal diagnosis of sleep apnoea. Pregnant or breastfeeding. Uncontrolled physical symptoms, as determined by medical assessment. Hepatic dysfunction as defined as serum alanine aminotransferase or bilirubin >3.5 x upper limit of normal. History of adverse reaction to benzodiazepine or the constituents in the placebo. Regular use of benzodiazepines (more than 2 doses within the past seven days). Antidepressant medication commenced or dose changed within the past month. Enrolment in another clinical trial with an investigational agent for anxiety or depression within 30 days of screening. Clinician predicted survival less than 14 days. Use of clozapine currently or within the past 4 weeks.
Outcome results
None listed