ANZCTR - Registration

Did you know?

The ANZCTR now automatically displays published trial results and simplifies the addition of trial documents such as unpublished protocols and statistical analysis plans.

These enhancements will offer a more comprehensive view of trials, regardless of whether their results are positive, negative, or inconclusive.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers

Trial registered on ANZCTR

Registration number

ACTRN12615000775516

Ethics application status

Approved

Date submitted

14/07/2015

Date registered

27/07/2015

Date last updated

15/04/2024

Date data sharing statement initially provided

8/01/2019

Date results provided

15/04/2024

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]

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

Condition category

Condition code

Musculoskeletal

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]

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]

Pain severity measured by the Pain Severity Score of the Brief Pain Inventory

Timepoint [1]

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]

Physical functioning measured by the Pain Interference Score of the Brief Pain Inventory

Timepoint [1]

2, 4, 6 and 12 weeks after randomisation

Secondary outcome [2]

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]

6 weeks after randomisation

Secondary outcome [3]

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]

Until recovery or up to 12 weeks

Secondary outcome [4]

Quality of life measured by SF-12

Timepoint [4]

2, 4, 6 and 12 weeks after randomisation

Secondary outcome [5]

Participants’ rating of global improvement measured by the global perceived effect scale

Timepoint [5]

2, 4, 6 and 12 weeks after randomisation

Secondary outcome [6]

Adverse events (e.g. constipation) measured by self report and by clinician report

Timepoint [6]

By self report - 2, 4, 6 and 12 weeks after randomisation
By clinician report - after each participant follow-up visit

Secondary outcome [7]

Work absenteeism measured by self report

Timepoint [7]

2, 4, 6 and 12 weeks after randomisation

Secondary outcome [8]

Use of other treatments or health care services measured by by self report

Timepoint [8]

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]

Cost-effectiveness analysis using use of treatments or health care services to generate cost and SF-12 to generate utility

Timepoint [9]

12 weeks

Secondary outcome [10]

Adherence to study medication measured by a diary (supported by returned medication count)

Timepoint [10]

Daily while on study medication

Secondary outcome [11]

Risk of misuse measured by the Current Opioid Misuse Measure

Timepoint [11]

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

Sex

Both males and females

Can healthy volunteers participate?

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

Completed

Date of first participant enrolment

Anticipated

1/02/2016

Actual

29/02/2016

Date of last participant enrolment

Anticipated

Actual

11/03/2021

Date of last data collection

Anticipated

11/03/2022

Actual

24/02/2022

Sample size

Target

346

Accrual to date

Final

347

Recruitment in Australia

Recruitment state(s)

NSW

Recruitment hospital [1]

Royal Prince Alfred Hospital - Camperdown

Recruitment hospital [2]

St Vincent's Hospital (Darlinghurst) - Darlinghurst

Recruitment postcode(s) [1]

2050 - Camperdown

Recruitment postcode(s) [2]

2010 - Darlinghurst

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

National Health and Medical Research Council

Address [1]

Level 1
16 Marcus Clarke Street
Canberra ACT 2601

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Human Research Ethics Committee, The University of Sydney

Ethics committee address [1]

Human Ethics Office
Margaret Telfer Building (K07)
University of Sydney
NSW 2006

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

16/01/2015

Approval date [1]

10/06/2015

Ethics approval number [1]

Project No. 2015-004

Ethics committee name [2]

Ethics Review Committee, Royal Prince Alfred Hospital

Ethics committee address [2]

Research Ethics and Governance Office
Royal Prince Alfred Hospital
Campderdown NSW 2050

Ethics committee country [2]

Australia

Date submitted for ethics approval [2]

15/09/2016

Approval date [2]

23/12/2016

Ethics approval number [2]

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

Prof Christine Lin

Address

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

Australia

Phone

+6128627 6267

Fax

sph.opal@sydney.edu.au

Contact person for public queries

Name

Hanan McLachlan

Address

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

Australia

Phone

+6128627 6267

Fax

sph.opal@sydney.edu.au

Contact person for scientific queries

Name

Christine Lin

Address

Country

Australia

Phone

+6128627 6267

Fax

sph.opal@sydney.edu.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

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?

Type	Citation	Link	Email	Other Details	Attachment
Study protocol				https://bmjopen.bmj.com/content/6/8/e011278
Statistical analysis plan	Jones, CMP, Lin C-WC, Day RO, Koes BW, Latimer J, Maher CG, McLachlan A, Billot L. OPAL: a randomised, placebo-controlled trial of opioid analgesia for the reduction of pain severity in people with acute spinal pain – a statistical analysis plan. Trials 2022 23:212	https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-022-06028-y

Results publications and other study-related documents

Documents added manually

Type	Is Peer Reviewed?	DOI	Citations or Other Details	Attachment
Study results article	Yes		Jones CMP, Day RO, Koes BW, Latimer J, Maher CG, M... [More Details]

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	OPAL: A randomised, placebo-controlled trial of opioid analgesia for the reduction of pain severity in people with acute spinal pain. Trial protocol.	2016	https://dx.doi.org/10.1136/bmjopen-2016-011278
Embase	OPAL: a randomised, placebo-controlled trial of opioid analgesia for the reduction of pain severity in people with acute spinal pain-a statistical analysis plan.	2022	https://dx.doi.org/10.1186/s13063-022-06028-y
Embase	Opioid analgesia for acute low back pain and neck pain (the OPAL trial): a randomised placebo-controlled trial.	2023	https://dx.doi.org/10.1016/S0140-6736%2823%2900404-X
Embase	The OPAL Trial Provides a Treasure of Evidence to Stop Using Opioids for Acute Neck and Back Pain: December 2023 Annals of Emergency Medicine Journal Club.	2023	https://dx.doi.org/10.1016/j.annemergmed.2023.10.002

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Did you know?

Documents added manually

Documents added automatically