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Trial registered on ANZCTR


Registration number
ACTRN12619000878178
Ethics application status
Approved
Date submitted
4/06/2019
Date registered
20/06/2019
Date last updated
10/08/2020
Date data sharing statement initially provided
20/06/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Venlafaxine for pain reduction in patients with knee osteoarthritis
Scientific title
A randomised controlled trial of venlafaxine to treat patients with knee osteoarthritis pain
Secondary ID [1] 298414 0
None
Universal Trial Number (UTN)
U1111-1234-6868
Trial acronym
PROVOKE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic pain 313124 0
Knee osteoarthritis 313125 0
Condition category
Condition code
Musculoskeletal 311600 311600 0 0
Osteoarthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Venlafaxine; 75 mg daily for 4 weeks and then increase to 150 mg daily for next 8 weeks; Tablet/oral administration; 12-week duration; Drug tablet return
Intervention code [1] 314663 0
Treatment: Drugs
Comparator / control treatment
Placebo (microcrystalline cellulose powder); Tablet/oral administration; 12-week duration
Control group
Placebo

Outcomes
Primary outcome [1] 320307 0
Change in knee pain measured on the visual analog scale (VAS, 0-100 mm) over 12 weeks
Timepoint [1] 320307 0
Baseline, 4, 8 and 12 weeks post intervention commencement.
Secondary outcome [1] 371139 0
Change in knee pain assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale from baseline to 4, 8 and 12 weeks
Timepoint [1] 371139 0
Baseline and 4, 8 and 12weeks post intervention commencement.
Secondary outcome [2] 371140 0
Change in physical function using WOMAC function subscale from baseline to 4, 8 and 12 weeks
Timepoint [2] 371140 0
Baseline and 4, 8 and 12 weeks post intervention commencement.
Secondary outcome [3] 371141 0
Change in quality of life measured by 36-item short-form health survey (SF-36)
Timepoint [3] 371141 0
Baseline and 12 weeks post intervention commencement.
Secondary outcome [4] 371142 0
Change in total painDETECT score using painDETECT questionnaire
Timepoint [4] 371142 0
Baseline and 12 weeks post intervention commencement.
Secondary outcome [5] 371143 0
Change in anxiety score measured by Hospital Anxiety and Depression Scale (HADS)-A
Timepoint [5] 371143 0
Baseline and 12 weeks post intervention commencement.
Secondary outcome [6] 371145 0
Change in Pain Catastrophizing Scale (PCS) scores measured by PCS
Timepoint [6] 371145 0
Baseline and 12 weeks post intervention commencement.
Secondary outcome [7] 371146 0
Change in Fibromyalgia scores measured by fibromyalgia-ness score
Timepoint [7] 371146 0
Baseline and 12 weeks post intervention commencement.
Secondary outcome [8] 371147 0
Change in Pain Disability Index (PDI) score measured by PDI
Timepoint [8] 371147 0
Baseline and 12 weeks post intervention commencement.
Secondary outcome [9] 371148 0
A simplified set of responder criteria focused on pain, function and patient global assessment developed by OMERACT (Outcome measures in Rheumatology)- OARSI (Osteoarthritis Research Society International), all time-points.
Timepoint [9] 371148 0
Baseline, 4, 8 and 12 weeks post intervention commencement.
Secondary outcome [10] 371340 0
Change in depression score measured by the Hospital Anxiety and Depression Scale (HADS)-D
Timepoint [10] 371340 0
Baseline and 12 weeks post intervention commencement.
Secondary outcome [11] 371341 0
Change in depression score measured by the Patient Health Questionnaire-9 (PHQ-9)
Timepoint [11] 371341 0
Baseline and 12 weeks post intervention commencement.
Secondary outcome [12] 371342 0
Change in depression score measured by the Beck Depression Inventory-II (BDI-II)
Timepoint [12] 371342 0
Baseline and 12 weeks post intervention commencement.

Eligibility
Key inclusion criteria
1. Age 40 to 80 years.
2. Knee pain for greater than or equal to 14 days of each month for >3 months.
3. Significant knee pain on most days (defined as a visual analogue scale (VAS) >40mm) on 100mm VAS pain.
4. Meet American College of Rheumatology (ACR) clinical criteria for knee OA confirmed by a rheumatologist.
Minimum age
40 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Severe knee OA (defined as joint space narrowing (JSN) on X-ray as Grade 3 using the OARSI atlas)
2. Prior knee joint replacement surgery.
3. Arthroscopy or open surgery in the study knee <12 months.
4. Intra-articular steroid injection <3 months.
5. Inflammatory arthritis (gout, rheumatoid arthritis, juvenile arthritis, etc).
6. Patients with a psychiatric disorder including major depressive disorder (Patient Health Questionnaire-9 score (PHQ-9)>9).
7. Contraindication to venlafaxine use including:
• Hypersensitivity to venlafaxine hydrochloride or to any excipients in the formulation;
• Current use of opioid medication;
• Concomitant use in patients taking monoamine oxidase inhibitors (MAOIs).
• History of seizures.
• Current use of venlafaxine or other antidepressants, amiodarone or domperidone.
• Pregnancy or breastfeeding.
• High cholesterol (total cholesterol >13.3 mmol/l).
• Hyponatremia (low amount of sodium in the blood <135 mmol/L).
• Increased risk of bleeding due to clotting disorder;
• History of increased intra-ocular pressure or closed angle glaucoma.
• Severe uncontrolled high blood pressure (supine diastolic blood pressure (SDBP) greater than or equal to 90 mm Hg).
• Heart attack within the last 3 months.
• Cirrhosis of the liver or abnormal liver function (alanine transaminase (ALT) 3x upper normal limit).
• Mild to moderate kidney impairment (estimated glomerular filtration rate (eGFR) <89 ml/min per 1.73 m2).
8. Inability to provide informed consent.

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 concealment will be ensured by the use of identical venlafaxine and placebo, and the use of central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
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 2
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/10/2020
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
116
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
TAS
Recruitment hospital [1] 13908 0
Royal Hobart Hospital - Hobart
Recruitment postcode(s) [1] 26681 0
7000 - Hobart

Funding & Sponsors
Funding source category [1] 302961 0
University
Name [1] 302961 0
University of Tasmania
Country [1] 302961 0
Australia
Primary sponsor type
University
Name
University of Tasmania
Address
Menzies Institute for Medical Research
17 Liverpool Street
Hobart
Tasmania 7000
Country
Australia
Secondary sponsor category [1] 302918 0
Individual
Name [1] 302918 0
Feng Pan
Address [1] 302918 0
Menzies Institute for Medical Research
17 Liverpool Street
Hobart
Tasmania 7000
Country [1] 302918 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303516 0
Tasmania Health & Medical Human Research Ethics Committee
Ethics committee address [1] 303516 0
Private Bag 1
Hobart
Tasmania 7001
Ethics committee country [1] 303516 0
Australia
Date submitted for ethics approval [1] 303516 0
21/08/2018
Approval date [1] 303516 0
15/04/2019
Ethics approval number [1] 303516 0
H0017601

Summary
Brief summary
Background: Osteoarthritis (OA) is a common, painful and disabling condition. Venlafaxine, a centrally acting antidepressant, has demonstrated analgesic effects in other chronic pain conditions.

Primary aim: To determine the effectiveness, safety and tolerability of venlafaxine (75-150mg daily) compared to placebo in reducing pain in knee OA patients using a randomised, placebo-controlled double-blind design over 12-week.

Primary hypothesis: Compared with placebo, in knee OA pain patients, 12-week treatment with venlafaxine will lead to a 10mm reduction in pain (assessed by 100mm visual analogue scale (VAS)).

Significance and Innovation: Positive results will have a substantial and immediate impact on OA pain management. It will provide compelling evidence that venlafaxine can reduce pain in OA patients. Such findings can be easily translatable into clinical practice, as venlafaxine is low cost, well tolerated and currently available in Australia.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 93934 0
Dr Feng Pan
Address 93934 0
Menzies Institute for Medical Research
17 Liverpool Street
Hobart
Tasmania 7000
Country 93934 0
Australia
Phone 93934 0
+61 3 6226 7705
Fax 93934 0
Email 93934 0
[email protected]
Contact person for public queries
Name 93935 0
Feng Pan
Address 93935 0
Menzies Institute for Medical Research
17 Liverpool Street
Hobart
Tasmania 7000
Country 93935 0
Australia
Phone 93935 0
+61 3 6226 7705
Fax 93935 0
Email 93935 0
[email protected]
Contact person for scientific queries
Name 93936 0
Feng Pan or Prof Graeme Jones
Address 93936 0
Menzies Institute for Medical Research
17 Liverpool Street
Hobart
Tasmania 7000
Country 93936 0
Australia
Phone 93936 0
+61 3 6226 7705
Fax 93936 0
Email 93936 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
2260Ethical approval    377719-(Uploaded-04-06-2019-14-34-19)-Study-related document.pdf



Results publications and other study-related documents

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