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Trial registered on ANZCTR


Registration number
ACTRN12620001143910
Ethics application status
Approved
Date submitted
22/09/2020
Date registered
2/11/2020
Date last updated
2/11/2020
Date data sharing statement initially provided
2/11/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
A Randomised, Double-Blind, Placebo Controlled Feasibility Study of Oral Lorazepam for Symptoms of Anxiety in Patients with Advanced Life-Limiting Disease
Scientific title
A Randomised, Double-Blind, Placebo Controlled Feasibility Study of Oral Lorazepam for Symptoms of Anxiety in Patients with Advanced Life-Limiting Disease
Secondary ID [1] 302340 0
None
Universal Trial Number (UTN)
Trial acronym
LORAZEPAM Study
Linked study record
None

Health condition
Health condition(s) or problem(s) studied:
Anxiety 319112 0
Condition category
Condition code
Mental Health 317073 317073 0 0
Anxiety

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 318632 0
Treatment: Drugs
Comparator / control treatment
Placebo as a size 3 gelatin capsule in opaque white containing maize starch.
Control group
Placebo

Outcomes
Primary outcome [1] 325162 0

Feasibility - study will be considered feasible if at least 21 participants are enrolled within 12 months,etc
Timepoint [1] 325162 0
12 months
Primary outcome [2] 325163 0
Feasibility- study will be considered feasible if at least 80% of enrolled participants completing 1 week of intervention and at least 80% of scheduled study assessments up to and including the End of Week 1 assessments
Timepoint [2] 325163 0
End of Week 1 assessments
Primary outcome [3] 325164 0
Participant retention on study and on study treatment at End of Week 1
Timepoint [3] 325164 0
End of Week 1
Secondary outcome [1] 387052 0
To assess participant retention and study assessment completion rates at 2 to 12 weeks
Timepoint [1] 387052 0
Week 2 to week 12

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Psychiatric disorder other than anxiety or depression.
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation involved contacting the holder of the allocation schedule who was "off-site" or at central administration site.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table from a statistic book
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Quantitative data will be summarised using descriptive statistics. Frequency counts and percentages will be used to summarise categorical variables. Mean (standard deviation) or median (interquartile range) will be used for continuous variables. Retention rates will be calculated overall and by arm at 1, 2, 4, 8 and 12 weeks. Thematic content analysis will be used for qualitative data from semi-structured interviews.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 17554 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [2] 17555 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [3] 17556 0
Sunshine Hospital - St Albans
Recruitment hospital [4] 17557 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [5] 17558 0
Royal Melbourne Hospital - Royal Park campus - Parkville
Recruitment postcode(s) [1] 31289 0
3000 - Melbourne
Recruitment postcode(s) [2] 31290 0
3065 - Fitzroy
Recruitment postcode(s) [3] 31291 0
3021 - St Albans
Recruitment postcode(s) [4] 31292 0
3084 - Heidelberg
Recruitment postcode(s) [5] 31293 0
3052 - Parkville

Funding & Sponsors
Funding source category [1] 306769 0
Charities/Societies/Foundations
Name [1] 306769 0
Peter MacCallum Cancer Centre Foundation
Address [1] 306769 0
305 Grattan Street, Melbourne , VIC-3000
Country [1] 306769 0
Australia
Funding source category [2] 306772 0
Charities/Societies/Foundations
Name [2] 306772 0
Bethlehem Griffiths Research Foundation
Address [2] 306772 0
476 Kooyong Rd, Caulfield South VIC 3162
Country [2] 306772 0
Australia
Primary sponsor type
Hospital
Name
Peter MacCallum Cancer Centre
Address
305 Grattan Street, Melbourne , VIC-3000
Country
Australia
Secondary sponsor category [1] 307322 0
None
Name [1] 307322 0
Address [1] 307322 0
Country [1] 307322 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306934 0
Peter MacCallum Cancer Centre
Ethics committee address [1] 306934 0
305 Grattan Street
Melbourne Vic 3000
Ethics committee country [1] 306934 0
Australia
Date submitted for ethics approval [1] 306934 0
27/04/2020
Approval date [1] 306934 0
04/09/2020
Ethics approval number [1] 306934 0
HREC/64219/PMCC

Summary
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.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 105502 0
Dr Nicola Atkin
Address 105502 0
Parkville Integrated Palliative Care Service
Peter MacCallum Cancer Centre
305 Grattan Street, Melbourne VIC 3000
Country 105502 0
Australia
Phone 105502 0
+613 8559 7960
Fax 105502 0
Email 105502 0
Nicola.Atkin@petermac.org
Contact person for public queries
Name 105503 0
Dr Nicola Atkin
Address 105503 0
Parkville Integrated Palliative Care Service
Peter MacCallum Cancer Centre
305 Grattan Street, Melbourne VIC 3000
Country 105503 0
Australia
Phone 105503 0
+613 8559 7960
Fax 105503 0
Email 105503 0
Nicola.Atkin@petermac.org
Contact person for scientific queries
Name 105504 0
Dr Nicola Atkin
Address 105504 0
Parkville Integrated Palliative Care Service
Peter MacCallum Cancer Centre
305 Grattan Street, Melbourne VIC 3000
Country 105504 0
Australia
Phone 105504 0
+613 8559 7960
Fax 105504 0
Email 105504 0
Nicola.Atkin@petermac.org

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Applications to access data for secondary studies or other research purposes can be forwarded to the sponsor for consideration.
All de-identified study data collected.
When will data be available (start and end dates)?
From 3 months up to 3 years following main publication.
Available to whom?
This will be considered on case-by-case basis.
Available for what types of analyses?
Any purpose.
How or where can data be obtained?
Data can be obtain by emailing the sponsor Peter MacCallum Cancer Centre (ocr@petermac.org)
What supporting documents are/will be available?
No other documents available
Summary results
No Results