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Trial registered on ANZCTR


Registration number
ACTRN12615000775516
Ethics application status
Approved
Date submitted
14/07/2015
Date registered
27/07/2015
Date last updated
12/06/2019
Date data sharing statement initially provided
8/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
OPAL: The first placebo-controlled trial of opioid analgesia for acute spinal pain
Scientific title
In patients with acute spinal pain, will taking a short course of an opioid analgesic, compared to placebo, in addition to receiving guideline care be more beneficial in reducing pain severity?
Secondary ID [1] 287083 0
Nil
Universal Trial Number (UTN)
Trial acronym
OPAL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute spinal pain: low back pain and/or neck pain 295593 0
Condition category
Condition code
Musculoskeletal 295869 295869 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Modified-release oxycodone tablets for up to 6 weeks, administered orally.

Participants will start at a dose of 5 mg, 2 times a day which will gradually be titrated up to the maximum dose of 10 mg, 2 times a day based on individual participant progress, tolerability and sedation score monitored by a study general practitioner at up to weekly intervals, up to 6 weeks in total. Treatment will continue until ‘adequate improvement’ (0 to 1 out of 10 pain for 3 consecutive days) or for a maximum of 6 weeks. When adequate improvement is achieved or after a maximum of 5 weeks of treatment, the study medication will be titrated down to cessation over 1 week.

Adherence to study medication will be monitored by a daily medication diary and returned medication count.

In addition all participants will receive guideline care, including advice (patient reassurance, staying active and avoiding bed rest) and, if required, other guideline-recommended treatments. For example, spinal manipulative therapy may be offered if pain is over 12 weeks in duration since onset and if more pain relief is required, simple analgesics or adjuvants may be provided in addition to the study medication in accordance to the WHO analgesic ladder. However, no concomitant opioid analgesics should be used.
Intervention code [1] 292323 0
Treatment: Drugs
Comparator / control treatment
Matching placebo tablets for up to 6 weeks, administered orally. Placebo tablets will contain colloidal silicon dioxide, microcrystalline cellulose, sodium starch glycolate and sodium stearyl fumarate in the tablet core, and brilliant blue FCF CI42090 in the coating.

As per the intervention group, participants will be monitored by a study general practitioner at up to weekly intervals, up to 6 weeks in total. Adherence to study medication will be monitored by a daily medication diary and returned medication count.

In addition all participants will receive guideline care, including advice (patient reassurance, staying active and avoiding bed rest) and, if required, other guideline-recommended treatments. For example, spinal manipulative therapy may be offered if pain is over 12 weeks in duration since onset and if more pain relief is required, simple analgesics or adjuvants may be provided in addition to the study medication in accordance to the WHO analgesic ladder. However, no concomitant opioid analgesics should be used.
Control group
Placebo

Outcomes
Primary outcome [1] 295547 0
Pain severity measured by the Pain Severity Score of the Brief Pain Inventory
Timepoint [1] 295547 0
The primary timepoint to determine treatment efficacy is over the 6-week treatment period.

The primary outcome will be collected at 2, 4, 6 and 12 weeks, and 6 and 12 months after randomisation.
Secondary outcome [1] 315829 0
Physical functioning measured by the Pain Interference Score of the Brief Pain Inventory
Timepoint [1] 315829 0
2, 4, 6 and 12 weeks after randomisation
Secondary outcome [2] 315830 0
Physical functioning measured by the Roland-Morris Disability Questionnaire (24 items, for participants reporting low back pain only) and Neck Disability Questionnaire (for participants reporting neck pain only)
Timepoint [2] 315830 0
6 weeks after randomisation
Secondary outcome [3] 315831 0
Time to recovery (recovery is defined as the average daily pain of 0 or 1 out of 10 for the past 7 consecutive days) measured by a daily diary
Timepoint [3] 315831 0
Until recovery or up to 12 weeks
Secondary outcome [4] 315832 0
Quality of life measured by SF-12
Timepoint [4] 315832 0
2, 4, 6 and 12 weeks after randomisation
Secondary outcome [5] 315833 0
Participants’ rating of global improvement measured by the global perceived effect scale
Timepoint [5] 315833 0
2, 4, 6 and 12 weeks after randomisation
Secondary outcome [6] 315834 0
Adverse events (e.g. constipation) measured by self report and by clinician report
Timepoint [6] 315834 0
By self report - 2, 4, 6 and 12 weeks after randomisation
By clinician report - after each participant follow-up visit
Secondary outcome [7] 315835 0
Work absenteeism measured by self report
Timepoint [7] 315835 0
2, 4, 6 and 12 weeks after randomisation
Secondary outcome [8] 315836 0
Use of other treatments or health care services measured by by self report
Timepoint [8] 315836 0
2, 4, 6 and 12 weeks after randomisation, and additionally at 6 and 12 months if participants are still experiencing low back pain and/or neck pain (>1/10).
Secondary outcome [9] 315837 0
Cost-effectiveness analysis using use of treatments or health care services to generate cost and SF-12 to generate utility
Timepoint [9] 315837 0
12 weeks
Secondary outcome [10] 315987 0
Adherence to study medication measured by a diary (supported by returned medication count)
Timepoint [10] 315987 0
Daily while on study medication
Secondary outcome [11] 315988 0
Risk of misuse measured by the Current Opioid Misuse Measure
Timepoint [11] 315988 0
3, 6 and 12 months after randomisation

Eligibility
Key inclusion criteria
Low back pain and/or neck pain no more than 12 weeks since onset, of at least moderate pain severity, and is considered by the treating doctor as appropriate for opioid analgesia.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Serious spinal pathology, contraindications to opioid analgesics, have taken an opioid analgesic for the current episode at a dose > 15mg of oral morphine equivalent per day for 5 or more consecutive days, spinal surgery in the preceding 6 months, scheduled or being considered for spinal surgery or interventional procedure, < 18 years of age, not having sufficient English or suitable translation is not available, or, for female participants only, planning conception, or is pregnant or breast-feeding.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
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)
NSW
Recruitment hospital [1] 12835 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 12836 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment postcode(s) [1] 25306 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 25305 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 291644 0
Government body
Name [1] 291644 0
National Health and Medical Research Council
Address [1] 291644 0
Level 1
16 Marcus Clarke Street
Canberra ACT 2601
Country [1] 291644 0
Australia
Primary sponsor type
Other
Name
The George Institute for Global Health
Address
Level 3,
50 Bridge St
Sydney NSW 2000
Country
Australia
Secondary sponsor category [1] 290313 0
None
Name [1] 290313 0
Address [1] 290313 0
Country [1] 290313 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294203 0
Human Research Ethics Committee, The University of Sydney
Ethics committee address [1] 294203 0
Human Ethics Office
Margaret Telfer Building (K07)
University of Sydney
NSW 2006
Ethics committee country [1] 294203 0
Australia
Date submitted for ethics approval [1] 294203 0
16/01/2015
Approval date [1] 294203 0
10/06/2015
Ethics approval number [1] 294203 0
Project No. 2015-004
Ethics committee name [2] 302300 0
Ethics Review Committee, Royal Prince Alfred Hospital
Ethics committee address [2] 302300 0
Research Ethics and Governance Office
Royal Prince Alfred Hospital
Campderdown NSW 2050
Ethics committee country [2] 302300 0
Australia
Date submitted for ethics approval [2] 302300 0
15/09/2016
Approval date [2] 302300 0
23/12/2016
Ethics approval number [2] 302300 0
Protocol No X16-0390 & HREC/16/RPAH/547

Summary
Brief summary
Low back pain and neck pain are extremely prevalent and are responsible for an enormous burden of disease both in Australia and globally. Strong analgesics, such as opioid analgesics, are recommended by clinical practice guidelines for people with acute low back pain or neck pain who are slow to recover and require more pain relief. The latest Australian data suggest that opioid analgesics are now the most widely prescribed medicine for low back pain and neck pain in general practice.

Despite the widespread use, there are no randomised, placebo-controlled trials evaluating opioid analgesics for acute low back pain or neck pain. Concerns regarding opioid use are further heightened due to the risks of adverse events, some of which can be serious such as opioid misuse, poisoning, and deaths.

Given the lack of evidence on efficacy and concerns regarding safety, there is an urgent need to understand whether opioid analgesics are beneficial for patients with acute low back pain and/or neck pain. OPAL is a randomised, placebo-controlled, triple-blinded trial that will investigate the judicious use of an opioid analgesic in 346 participants with acute low back pain and/or neck pain who are slow to recover. Participants will be recruited from general practice and randomised to receive the opioid analgesic (modified-release oxycodone up to 20 mg per day) or placebo in addition to guideline care for up to 6 weeks. The primary outcome will be pain severity measured up to 12 months with treatment efficacy over the 6-week treatment period being the primary time point for analysis. Medication-related adverse events will be assessed and a cost-effectiveness analysis will be conducted. We will additionally assess long-term use and risk of misuse of opioid analgesics for up to 12 months.

The results of this study will be critical in providing robust evidence to inform the quality use of opioid analgesia in acute low back pain and neck pain. The results will also influence international clinical practice guidelines and most importantly, improve care for patients suffering acute spinal pain.
Trial website
http://www.georgeinstitute.org.au/projects/opal-the-first-placebo-controlled-trial-of-opioid-analgesia-for-acute-spinal-pain
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 58766 0
A/Prof Christine Lin
Address 58766 0
Sydney School of Public Health, Faculty of Medicine and Health, The University of Sydney and Institute for Musculoskeletal Health

Level 10 North, King George V Building, Royal Prince Alfred Hospital (C39) PO Box 179, MISSENDEN ROAD NSW 2050
Country 58766 0
Australia
Phone 58766 0
+6128627 6267
Fax 58766 0
Email 58766 0
sph.opal@sydney.edu.au
Contact person for public queries
Name 58767 0
Ms Hanan McLachlan
Address 58767 0
Musculoskeletal Health Sydney
School of Public Health
The University of Sydney
Level 10 North, King George V Building, Royal Prince Alfred Hospital (C39)
PO Box 179, MISSENDEN ROAD NSW 2050
Country 58767 0
Australia
Phone 58767 0
+6128627 6267
Fax 58767 0
Email 58767 0
sph.opal@sydney.edu.au
Contact person for scientific queries
Name 58768 0
A/Prof Christine Lin
Address 58768 0
Sydney School of Public Health, Faculty of Medicine and Health, The University of Sydney and Institute for Musculoskeletal Health

Level 10 North, King George V Building, Royal Prince Alfred Hospital (C39) PO Box 179, MISSENDEN ROAD NSW 2050
Country 58768 0
Australia
Phone 58768 0
+6128627 6267
Fax 58768 0
Email 58768 0
sph.opal@sydney.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
We have no plans to make individual participant data publicly available at this stage, and have not obtained ethical approval for this. However, after the study results are published, contacts can be made with the study investigators to enquire about access to the study data for IPD analysis.
What supporting documents are/will be available?
Study protocol
How or where can supporting documents be obtained?
Type [1] 959 0
Study protocol
Citation [1] 959 0
Link [1] 959 0
Email [1] 959 0
Other [1] 959 0
https://bmjopen.bmj.com/content/6/8/e011278
Attachment [1] 959 0
Summary results
No Results