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Trial registered on ANZCTR


Registration number
ACTRN12619001082190
Ethics application status
Approved
Date submitted
18/06/2019
Date registered
6/08/2019
Date last updated
18/10/2019
Date data sharing statement initially provided
6/08/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Serotonin Noradrenaline Reuptake Inhibitors (SNRI) medications for the treatment of osteoarthritis pain (STOP) trial
Scientific title
Venlafaxine compared to duloxetine for the treatment of osteoarthritis pain: A double-blind, randomised, non-inferiority trial
Secondary ID [1] 298524 0
Nil known
Universal Trial Number (UTN)
U1111-1228-2143
Trial acronym
STOP (SNRI medications for the treatment of osteoarthritis pain)
Linked study record
Not Applicable (N/A)

Health condition
Health condition(s) or problem(s) studied:
Knee osteoarthritis 313332 0
Condition category
Condition code
Musculoskeletal 311771 311771 0 0
Osteoarthritis
Anaesthesiology 311772 311772 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Inert gelatin placebo taken orally once a day in 1 opaque microcellulose capsule for 1 week; Venlafaxine (75mg) taken orally once a day in 1 opaque microcellulose capsule for 1 week; Venlafaxine (150mg) taken orally once a day in 1 opaque microcellulose capsules for 7 weeks (trial endpoint); Venlafaxine (75mg) taken orally once a day in 1 opaque microcellulose capsule for 2 weeks (tapering dose). Participant adherence will be monitored through the use of daily drug diaries, weekly follow up phone calls and the return of any unused medications at the end of the intervention period.
Intervention code [1] 314773 0
Treatment: Drugs
Comparator / control treatment
Inert gelatin placebo taken orally once a day in 1 opaque microcellulose capsule for 1 week; Duloxetine (30mg) taken orally once a day in 1 opaque microcellulose capsule for 1 week; Duloxetine (60mg) taken orally once a day in 1 opaque microcellulose capsules for 7 weeks (trial endpoint); Duloxetine (30mg) taken orally once a day in 1 opaque microcellulose capsule for 2 weeks (tapering dose). Participant adherence will be monitored through the use of daily drug diaries, weekly follow up phone calls and the return of any unused medications at the end of the intervention period
Control group
Active

Outcomes
Primary outcome [1] 320457 0
Change in the Brief Pain Inventory average pain rating.
Timepoint [1] 320457 0
Weekly from baseline to end of week 9.
Secondary outcome [1] 371650 0
Change in the Brief Pain Inventory worst pain rating.
Timepoint [1] 371650 0
Weekly from baseline to end of week 9.
Secondary outcome [2] 371651 0
Change in the Brief Pain Inventory least pain rating.
Timepoint [2] 371651 0
Weekly from baseline to the end of Week 9.
Secondary outcome [3] 371652 0
Change in the Brief Pain Inventory pain right now rating.
Timepoint [3] 371652 0
Weekly from baseline to end of Week 9
Secondary outcome [4] 371653 0
Change in symptoms of anxiety and depression (hospital anxiety and depression scale)
Timepoint [4] 371653 0
Measured at baseline and the end of week 9.
Secondary outcome [5] 371654 0
Change in physical function (lower limb tasks questionnaire)
Timepoint [5] 371654 0
Measured at baseline and the end of week 9.
Secondary outcome [6] 371655 0
Change in quality of life (EuroQOL5D)
Timepoint [6] 371655 0
Measured at baseline and the end of week 9.
Secondary outcome [7] 371656 0
Patient global impression of change with respect to their overall osteoarthritis condition
Timepoint [7] 371656 0
End of week 9 (post baseline)
Secondary outcome [8] 371657 0
Number of treatment responders (> or = to 50% improvement in brief pain inventory average pain score)
Timepoint [8] 371657 0
Calculated from measurements at baseline and the end of week 9.
Secondary outcome [9] 371658 0
Number of treatment responders (> or = 30% improvement in brief pain inventory average pain score)
Timepoint [9] 371658 0
Calculated from measurements at baseline and the end of week 9.

Eligibility
Key inclusion criteria
Males and females at least 40 years old who have radiographic evidence of knee osteoarthritis and meet the American College of Rheumatology clinical criteria for the diagnosis of knee osteoarthritis.
A history of knee pain for > 14 days days of each month for 3 months or more.
A brief pain inventory average pain rating of at least 4/10 at the time of initial screening
Minimum age
40 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Current use of antidepressant medication or any other medication with a serotonergic effect; use of a MAOI inhibitor in the last 14 days; narrow-angle glaucoma; BMI > or = to 40; diagnosis of any other type of arthritis; joint injection or surgery on the index knee within the last 3 months; impending surgery in the next 3 months; medical contraindication to the use of rescue medications (acetaminophen and NSAIDs); patients taking any excluded medications that cannot be discontinued; women who are pregnant, breast feeding or planning to get pregnant; previous diagnosis of a major psychiatric disorder; history of alcoholism; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 100 IU/L or total bilirubin > 27.4 umol/L; glomerular filtration rate of < 30ml/min; a history of myocardial infarction in the last 12 months, QTc interval > 500ms, unstable coronary artery disease or recent unexplained cardiac symptoms; uncontrolled hypertension (> or = to 140mmHg systolic or > or = to 90mmHg diastolic BP); a history of seizures; a history of multiple falls in the last 12 months; current use of warfarin; an inability to perform psychophysical testing.

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)
The study personnel conducting the recruitment and screening procedures will be unaware of the allocation schedule, which will be password protected and kept "off site" at the clinical trials pharmacy.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomised in a 1:1 ratio using a computer generated randomisation schedule with permuted blocks of random size.
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 3 / Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
As this is a non-inferiority trial, sample size estimates were carried out consistent with established regulatory guidelines. Results from Chappell et al were used to inform the estimate, where Duloxetine led to a mean (SD) 44% (27%) improvement in Brief Pain Inventory 24hr average pain in people with knee OA. Assuming a clinically important difference of 30%, power of 0.9, a of 0.025 and a 20% discontinuation rate, 146 participants are needed for a sufficiently powered appraisal of non-inferiority.

Linear or generalised linear mixed effects models will be used to assess the treatment effects of Venlafaxine and Duloxetine on the primary outcome measure (BPI average pain).Two levels of analysis will be performed 1) intention-to-treat and 2) according to treatment received. Secondary outcomes will be also analysed and compared between groups using linear or generalised linear mixed effects models. Analysis of differential versus non-differential occurrence of missing observations will be carried out to assure that any missing data are not systematic and further, to account for potential bias in the intention-to-treat analyses. We will report our imputation methods, and we will perform a sensitivity analysis, examining effects on the outcomes reported, with explicit reporting of missing observations and withdrawals.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
2/09/2019
Actual
30/09/2019
Date of last participant enrolment
Anticipated
1/04/2021
Actual
Date of last data collection
Anticipated
30/06/2021
Actual
Sample size
Target
146
Accrual to date
10
Final
Recruitment outside Australia
Country [1] 21616 0
New Zealand
State/province [1] 21616 0
Auckland

Funding & Sponsors
Funding source category [1] 303070 0
Government body
Name [1] 303070 0
Health Research Council of New Zealand
Country [1] 303070 0
New Zealand
Primary sponsor type
Hospital
Name
Waitemata District Health Board
Address
North Shore Hospital, 124 Shakespeare Rd, Takapuna, Auckland 0620
Country
New Zealand
Secondary sponsor category [1] 303053 0
None
Name [1] 303053 0
n/a
Address [1] 303053 0
n/a
Country [1] 303053 0
Other collaborator category [1] 280737 0
University
Name [1] 280737 0
Auckland University of Technlogy
Address [1] 280737 0
90 Akoranga Drive, Northcote, Auckland, 0627
Country [1] 280737 0
New Zealand
Other collaborator category [2] 280738 0
University
Name [2] 280738 0
University of Sherbrooke
Address [2] 280738 0
Université de Sherbrooke
Local E5-1283
Sherbrooke (Québec)
CANADA J1K 2R1
Country [2] 280738 0
Canada

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303618 0
Central Health and Disability Ethics Committee
Ethics committee address [1] 303618 0
Ethics committee country [1] 303618 0
New Zealand
Date submitted for ethics approval [1] 303618 0
28/02/2019
Approval date [1] 303618 0
03/04/2019
Ethics approval number [1] 303618 0
19/CEN/27

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 94282 0
Dr David Rice
Address 94282 0
Waitemata Pain Services, Level 10, North Shore Hospital, 124 Shakespeare Road, Takapuna, Auckland 0622
Country 94282 0
New Zealand
Phone 94282 0
+64 9 4868900
Fax 94282 0
Email 94282 0
david.rice@aut.ac.nz
Contact person for public queries
Name 94283 0
David Rice
Address 94283 0
Waitemata Pain Services, Level 10, North Shore Hospital, 124 Shakespeare Road, Takapuna, Auckland 0622
Country 94283 0
New Zealand
Phone 94283 0
+64 9 4868900
Fax 94283 0
Email 94283 0
david.rice@aut.ac.nz
Contact person for scientific queries
Name 94284 0
David Rice
Address 94284 0
Waitemata Pain Services, Level 10, North Shore Hospital, 124 Shakespeare Road, Takapuna, Auckland 0622
Country 94284 0
New Zealand
Phone 94284 0
+64 9 4868900
Fax 94284 0
Email 94284 0
david.rice@aut.ac.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Participant consent has not been given.


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
No additional documents have been identified.