Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001423707
Ethics application status
Approved
Date submitted
31/08/2022
Date registered
7/11/2022
Date last updated
2/10/2023
Date data sharing statement initially provided
7/11/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Digital Support For People With Chronic Pain Who Are Reducing Prescription Opioids
Scientific title
Digital Support For People With Chronic Pain Who Are Reducing Prescription Opioids - A Double-Blind Randomised Controlled Trial Evaluating The Feasibility, Acceptability, And Efficacy
Secondary ID [1] 307879 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Pain 327508 0
Opioid Analgesics 327509 0
Opioid Tapering 327510 0
Condition category
Condition code
Anaesthesiology 324620 324620 0 0
Pain management
Public Health 324621 324621 0 0
Health promotion/education

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients with chronic non-cancer pain on long-term opioid therapy who are tapering opioids under supervision of their doctor will be randomised to two groups.

Participants randomised to group 1 will initially receive an educational video of approximately 10 minutes to watch. The video which is specifically designed for this study has information about a) Chronic pain and opioid medications, b) What to expect while reducing opioid dose? c) How reducing opioid dose can help? d) Pain management techniques that can help while reducing opioid dose, e) What did other patients experience when they reduced their opioid dose? The video will be followed by daily text messages sent to their mobile phone for 12 weeks, twice per day, between 9 AM and 5 PM. These messages will provide further information, education, and support mentioned above. All participants in group 1 will receive the same messages in the same order. Participants are not required to respond to the SMS system (i.e., one-way message).
Participants in group 1 will receive all scheduled messages, unless they choose to withdraw from the study or from receiving text messages. Delivery of the text messages will be automatically logged by the SMS software.
Intervention code [1] 324342 0
Behaviour
Intervention code [2] 324416 0
Treatment: Other
Comparator / control treatment
Group 2 will receive the educational video to watch which is specifically designed for this study and is similar to the video in group 1 but lacking only information about text messaging.

Both groups will receive usual care. Usual care in this study is defined as the care that each participant is receiving at the discretion of their care providers (GP, Pain Specialist, etc.). This may include multidisciplinary care involving a combination of medical (procedural, pharmacological), psychological (group or individual cognitive behaviour therapy for pain), and physiotherapy interventions (exercise programs delivered individually or in a group). Participants in the current study are those who are tapering their opioid medications under the guidance of their physician. The decision to taper and tapering schedules are negotiated between the patient and their physician. Hence, the rate of opioid tapering is patient-centred and may not be standardised. The attending physician is responsible for the monitoring and management of withdrawal symptoms and other possible adverse events of opioid tapering. Digital support (or participation in the study) does not intervene in the clinical decision to reduce opioid dose, the rate of dose reduction, or any other care that participants might be receiving.
Control group
Active

Outcomes
Primary outcome [1] 332439 0
The primary outcome in this trial is pain intensity and interference measured at 12 weeks after enrolment using a validated composite outcome measure, the 3-item Pain, Enjoyment of Life and General Activity scale (PEG).
Timepoint [1] 332439 0
The PEG will be administered at baseline and then every 4 weeks during the study for 12 weeks.
Secondary outcome [1] 413500 0
Severity of depression symptoms 12 weeks after enrolment. We will measure the severity of depression symptoms with the Patient Health Questionnaire-2 (PHQ-2).
Timepoint [1] 413500 0
The PHQ-2 will be administered at baseline and then every 4 weeks during the study for 12 weeks.
Secondary outcome [2] 413502 0
Participant’s rating of global improvement 12 weeks after enrolment. We will measure global improvement using the Patient Global Impression of Change (PGIC) scale.
Timepoint [2] 413502 0
The PGIC scale will be administered 12 weeks after enrolment.
Secondary outcome [3] 413503 0
Pain self-efficacy 12 weeks after enrolment. We will measure pain self-efficacy using the 2-item Pain Self-Efficacy Questionnaire (PSEQ-2).
Timepoint [3] 413503 0
The PSEQ-2 will be administered at baseline and then every 4 weeks during the study for 12 weeks.
Secondary outcome [4] 413504 0
Percentage of opioid dose change 12 weeks after enrolment: To measure opioid dose change, we will use two sources of information: 1) participants’ self-reports of their current medication (i.e., drug names, doses, regimen) at baseline and then every 4 weeks; 2) prescription history obtained from The National Real Time Prescription Monitoring system (RTPM). The RTPM is a nationally implemented system in Australia which collects prescribing and dispensing information about monitored medicines via the electronic prescription exchange services. The National Data Exchange component of the RTPM captures information from state and territory regulatory systems, prescribing and dispensing software, and a range of external data sources. The total daily dose (TDD) of opioid will be converted to mg of oral morphine equivalents (OME) and the percentage of change from baseline will be calculated.
Timepoint [4] 413504 0
Opioid medication/dose will be evaluated at baseline and then every 4 weeks during the study for 12 weeks.
Secondary outcome [5] 413505 0
Cumulative incidence of withdrawal symptoms 12 weeks after enrolment. We will evaluate the experience of withdrawal-like symptoms during the study period using a binary question (Yes/No) in online surveys followed by an open-ended prompt for patients to explain the experienced symptoms: "Have you experienced any withdrawal symptoms in the past week? Please explain if yes"
Timepoint [5] 413505 0
Incidence of withdrawal symptoms will be evacuated every 4 weeks during the study for 12 weeks.
Secondary outcome [6] 413506 0
Concerns about pain 12 weeks after enrolment: Pain catastrophising cognitions will be measured using the 2-item Concerns About Pain scale (CAP-6)
Timepoint [6] 413506 0
CAP-6 will be administered at baseline and then every 4 weeks during the study for 12 weeks.
Secondary outcome [7] 413507 0
Acceptability of digital support will be measured using a survey at the end of the study period. The survey contains Likert scales and open-ended questions about the usefulness, readability, and acceptability of the digital support. We will also conduct a semi-structured interview at the end of the study period in both groups.
Timepoint [7] 413507 0
12 weeks after enrolment
Secondary outcome [8] 413508 0
Feasibility of digital support will be evaluated at the end of the study according to the number of messages delivered/not delivered which will be recorded automatically by the text message system. To measure participant disposition, we will also report on (1) the recruitment process and percentage of participants enrolled from each recruitment method as assessed by self-report in an online screening form; (2) the number of candidate participants who were excluded and reasons for exclusion based on the online screening form; (3) the number of candidates who chose not to enter the trial and the reasons for not entering as noted in the patient recruitment database; (4) the use of concomitant care (e.g., physiotherapy, psychotherapy) as assessed by self-report in baseline assessment form; (5) all protocol deviations that may impact the interpretation of the trial results based on trial process log; (6) the number of withdrawals from each treatment group, including patients lost to follow up, and the reasons for withdrawals based on REDCap records; and (7) the types, rates, and reasons for non-adherence with treatment in each treatment group (e.g., not watching the video) based on REDCap records and the SMS software.
Timepoint [8] 413508 0
12 weeks after enrolment
Secondary outcome [9] 413509 0
Potentially adverse and unwanted events 12 weeks after enrolment. To evaluate this, participants will complete the 20-item Negative Effects Questionnaire.
Timepoint [9] 413509 0
12 weeks after enrolment
Secondary outcome [10] 413815 0
Severity of anxiety symptoms 12 weeks after enrolment. We will measure the severity of anxiety symptoms with the Generalised Anxiety Disorder-2 (GAD-2).
Timepoint [10] 413815 0
The GAD-2 will be administered at baseline and then every 4 weeks during the study for 12 weeks.
Secondary outcome [11] 413816 0
Opioid tapering self-efficacy 12 weeks after enrolment. We will measure self-efficacy in reducing opioid medications using the Opioid Tapering Self-Efficacy Questionnaire (OTSEQ).
Timepoint [11] 413816 0
The OTSEQ will be administered at baseline and then every 4 weeks during the study for 12 weeks.

Eligibility
Key inclusion criteria
- A resident of Australia
- Age greater than or equal to 18 years
- Having a chronic (greater than or equal to 3 months) non-cancer pain condition
- Using opioid analgesics for at least four weeks before enrolment
- Has started or is starting voluntarily reducing opioid dose under the supervision of a physician (GP or Specialist)
- Willing to provide contact details of their physician (GP or Specialist)
- Able to understand written and spoken English well
- Owns a mobile phone that can receive text messages
- Has access to the internet via their mobile phone
- Able to give informed consent and comply with the study procedures
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Having opioid or other substance use disorder
- Having a poorly controlled or unstable mental illness
- Suicidal ideation or attempt in the past 12 months
- Major surgery in the past 6 months or scheduled in the next 3 months
- Participation in another clinical trial concurrently
- Pregnant

Study design
Purpose of the study
Educational / counselling / training
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The person who determines if a subject is eligible for inclusion in the trial is unaware, when this decision is made, to which group the subject will be allocated. Allocation is concealed as it is done by REDCap with no access to the imbedded random table for the person who enrols participants.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table generated by https://www.randomizer.org/ and imbedded in REDCap.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample size
With a 2-sided a level of 0.05, a study power of 0.8, a standard deviation (SD) of 2 points in the PEG scale score (primary outcome measure), and assuming a 20% drop-out rate, we require 74 participants in total to detect 1.5 point difference (MCID of PEG, Cohen’s d = 0.75) between the two study groups in mean PEG score after 12 weeks.
Statistical analysis
Researchers conducting analyses will be blinded to the group status. Our primary outcome is patients’ level of PEG total score at 12 weeks post-randomisation. The study primary hypothesis (H1) is that the PEG scale total score at 12 weeks after randomisation is lower in the intervention compared to the control group. To test this hypothesis, a linear mixed model containing fixed effects of treatment group, time, and time x group interaction as well as baseline values of the outcome, will be used. A planned contrast (i.e., between-group difference at week 12) will be used to test the study primary hypothesis. We will also include the measures of PEG scale at 4 and 8 weeks after randomisation in our primary analysis model, so that in the case of missingness at 12 weeks, the model can use these data to obtain a better estimate at 12 weeks despite the missingness by applying maximum likelihood methods (i.e., including the random effect of participants and fixed effect of time). This approach provides valid inferences under the assumption that the mechanism of missing data is ignorable (or Missing At Random). To account for correlation between repeated measures at 4, 8, and 12 weeks, a random intercept will be included at the subject level. We will explore if baseline adjusted model (i.e., including baseline values of the dependent variable in the model as covariate) can improve the precision of the estimates based on the fit statistics and residual distribution. Normal distribution of the residuals will be tested. If departed from normality, first we will look for a more appropriate distribution shape and data will be transformed if appropriate to approximate residuals to normality.
Similarly, linear mixed model will be used to analyse the study secondary outcomes with repeated measures after randomisation (e.g., emotional functioning). To analyse continuous clinical secondary outcomes, we will use the same model as for the primary analysis. This involves linear mixed models that incorporate outcome measures at all available time points, along with a time by treatment interaction term that enables estimation of the difference between arms at each time point. For binary secondary outcomes, we will employ a logistic mixed effects model, again including the outcome at all available time points and with two levels. The statistical significance will be defined as P < 0.05 (two-sided) and the effect estimates will be reported with corresponding Confidence Intervals (CIs). Cohen’s d (effect size) will be calculated based on the estimates and standard errors. Analyses will be conducted using SAS software (v 9.4, SAS Institute Inc., Cary, NC, USA).
Explorative analysis
The PEG scale total score is the primary outcome measure to test the efficacy of the intervention according to the pre-specified MCID for this measure. However, each of the PEG scale items will also be analysed and reported separately with explorative aims. Explorative analyses will be done to investigate trends of change in outcomes within- and between-group (i.e., group by time interaction effect) and potential moderating and mediating factors. Model statement and parameters (i.e., estimation method, covariance structure) will be determined based on the fit statistics and residuals distribution. In addition to marginal linear mixed models (where time is a categorical variable), linear mixed models (where time is a continuous variable) with random intercept and random slope will also be conducted. Pairwise contrasts will be done to compare the outcomes between the two groups at weeks 4 and 8. In these explorative analyses, P value adjustment will be done to account for multiple comparisons according to the Holm–Bonferroni method.
Sensitivity analyses and missing data imputation
Sensitivity analyses will be done with both per-protocol and intention-to-treat (ITT) analyses based on drop-outs and missing data, as well as based on participants’ compliance (e.g., refusing to receive SMS if allocated to). For the analyses where all levels of the repeated measures are included in the model as dependent variable, missing data will be imputed by the mixed-model analysis without any further ad hoc imputation unless when only a baseline value is available. In such case, selective imputation will be done using the baseline observation carry forward method.
Qualitative analysis
For feasibility and acceptability outcomes, a mixed-method analysis will be conducted on quantitative-qualitative data. Transcripts and digital notes will be entered into NVivo (version 12, QSR International). Thematic analysis using an inductive approach will be followed. The Consolidated Framework for Implementation Research will be used to organise implementation barriers and facilitators into major constructs.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
10/03/2023
Actual
10/03/2023
Date of last participant enrolment
Anticipated
9/03/2024
Actual
Date of last data collection
Anticipated
10/06/2024
Actual
Sample size
Target
74
Accrual to date
27
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC

Funding & Sponsors
Funding source category [1] 312153 0
Charities/Societies/Foundations
Name [1] 312153 0
Ernest Heine Family Foundation
Country [1] 312153 0
Australia
Primary sponsor type
University
Name
University of Sydney
Address
Pain Management Research Institute, Faculty of Medicine & Health, The University of Sydney.
Address PMRI, Ground Floor, Douglas Building, Royal North Shore Hospital, 1 Reserve Rd, St Leonards NSW 2065.
Country
Australia
Secondary sponsor category [1] 313681 0
None
Name [1] 313681 0
Address [1] 313681 0
Country [1] 313681 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311544 0
Northern Sydney Local Health District Human Ethics Committee
Ethics committee address [1] 311544 0
Research Ethics and Governance Manager | NSLHD Research Office
Level 13 Kolling Building, Royal North Shore Hospital, Reserve Road, St Leonards, NSW, 2065
Ethics committee country [1] 311544 0
Australia
Date submitted for ethics approval [1] 311544 0
31/08/2022
Approval date [1] 311544 0
02/11/2022
Ethics approval number [1] 311544 0
2022/ETH01795

Summary
Brief summary
This double-blind randomised controlled trial will investigate the the feasibility, acceptability, and efficacy of digital support to improve pain and well-being of people with chronic pain who are reducing prescription opioids. Participants will be patients with chronic non-cancer pain who are commencing prescription opioid tapering (dose reduction). 74 participants who meet the selection criteria will be randomized to receive either an educational video followed by text messages for 12 weeks (group 1) or an educational video (group 2) in addition to their usual care. The digital support intends to increase the self-efficacy to taper prescription opioids. This includes pain management and opioid tapering information, as well as supportive content. The study will evaluate the efficacy of the intervention in improving pain and well-being as the primary objective.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 121482 0
Prof Paul Glare
Address 121482 0
Pain Management Research Institute Ground floor, Douglas Building, Royal North Shore Hospital, 1 Reserve Road, ST LEONARDS, NSW, 2065
Country 121482 0
Australia
Phone 121482 0
+61 2 9463 1526
Fax 121482 0
Email 121482 0
paul.glare@sydney.edu.au
Contact person for public queries
Name 121483 0
Dr Ali Gholamrezaei
Address 121483 0
Pain Management and Research Centre. Ground floor, Douglas Building Royal North Shore Hospital, St. Leonards 2065, NSW, Australia
Country 121483 0
Australia
Phone 121483 0
+61 2 9463 1500
Fax 121483 0
Email 121483 0
ali.gholamrezaei@sydney.edu.au
Contact person for scientific queries
Name 121484 0
Dr Ali Gholamrezaei
Address 121484 0
Pain Management and Research Centre. Ground floor, Douglas Building Royal North Shore Hospital, St. Leonards 2065, NSW, Australia
Country 121484 0
Australia
Phone 121484 0
+61 2 9463 1500
Fax 121484 0
Email 121484 0
ali.gholamrezaei@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
Not in ethics approval


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseText messaging intervention to support patients with chronic pain during prescription opioid tapering: Protocol for a double-blind randomised controlled trial.2023https://dx.doi.org/10.1136/bmjopen-2023-073297
N.B. These documents automatically identified may not have been verified by the study sponsor.