Perioperative Vitamin C to Reduce Persistent Pain After Total Knee Arthroplasty

Study Overview
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Brief Summary
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Phase II Multicentre, pilot, parallel-group, blinded, 1:1 randomized controlled trial to determine the feasibility of conducting a larger definitive trail of using vitamin C to reduce persistent pain in patients undergoing total knee arthroplasty surgery.

Detailed Description
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PROVISION is a multicentre, pilot, parallel-group, blinded, randomized controlled trial of 100 patients undergoing total knee arthroplasty surgery. Consented eligible patients will be randomized to receive vitamin C: 2000 mg taken orally within 4 hours of the start of surgery, followed by 500 mg of vitamin C taken twice daily from post-operative day 1 to day 56 (8 weeks). Patient in the control group will receive placebo lactose monohydrate capsules. Study medications will be prepared to look similar and labelled as per regulatory requirements. Patients will follow up on post-operative days 1-3, weeks 2,4,6, and 8 post-operatively, and at 3- and 12-months post-operatively to report on pain, opioid and analgesic consumption, medication adherence, adverse events, functional, mood, and quality of life outcomes.

Official Title
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PeRiOperative VItamin C to Reduce perSistent paIn After tOtal kNee Arthroplasty (PROVISION): a Pilot Multicentre Randomized Controlled Trial

Conditions
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Chronic Pain, Knee Pain Chronic, Post Operative Pain

Intervention / Treatment
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* Drug: Vitamin C
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients >18 years old Undergoing a unilateral or bilateral primary total knee arthroplasty for advanced osteoarthritis of the knee Exclusion Criteria: TKA for infection (septic joint), fracture, ankylosing spondylitis, lupus, or psoriatic arthritis History of kidney stones, acute or chronic renal failure, hemochromatosis, or glucose-6-phosphate deficiency Unlikely to comply with follow-up (e.g., no fixed address, plans to move out of town) Language difficulties that would impede valid completion of questionnaires Planned staged bilateral TKA Treating surgeon deems patient inappropriate for inclusion in trial Any allergy or sensitivity to milk Pregnant or planning to become pregnant during the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Preoperative Vitamin C capsules | Drug: Vitamin C<br>* Drug: Patients in the intervention group will receive 2g Vitamin C orally within 4 hours of the start of the surgery followed by 500 mg of Vitamin C to be taken orally twice a day from post-op day1 to day 56.<br>* Other names: Ascorbic Acid;|
| Placebo Comparator: Placebo<br>Preoperative placebo capsules | Drug: Placebo<br>* Drug: Patients in the placebo group will receive identical placebo capsules taken orally within 4 hours of the start of the surgery followed by placebo capsules taken orally twice a day from post-op day 1 to day 56.<br>* Other names: Lactose (Monohydrate);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Study will determine feasibility of enrolling, recruiting, and follow-up with patients. | The study will assess the feasibility of enrolling, recruiting, and following-up with patients undergoing a primary total knee arthroplasty (TKA) through active monitoring of recruitment/enrollment rates on a monthly basis for a total of one year using excel trackers. The follow-up rate of patients will be assessed at 12 months based on completion of all 12 month questionnaires. | 12 months | 
| Clinical site compliance | Clinical site compliance with trial protocol will be determined based on number of protocol deviations at each site as logged on the deviation logs. This will be assessed on a monthly basis for a full year to maintain active monitoring of compliance. | 12 months | 
| Resource Assessment | This pilot study will help determine the resources required for larger definitive trial based on critical analysis of recruitment trackers to assess time spent on recruitment/enrollment. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of persistent pain | Pain intensity measured using 0-10 Numeric Rating Scale (NRS) scale at rest and movement | 3 months and 12 months | 
| Qualities and characteristics of persistent pain | Pain qualities measured using the 0-10 scale of the Short Form McGill Pain Questionnaire 2 (SF-MPQ-2) | 3 months and 12 months | 
| Persistent Neuropathic Pain | Neuropathic pain assessed on a binary scale of Yes or No using the Douleur Neuropathique 4 (DN4) symptoms interview | 3 months and 12 months | 
| Acute and chronic analgesic consumption | Analgesic and oral morphine-equivalent opioid consumption | Day of surgery, post-operative day 1-3, 3 months, and 12 months | 
| Development of Complex Regional Pain Syndrome (CRPS) | Presence of CRPS measured by a physical assessment of sensory, vasomotor, sudomotor/edema, and motor/tropic categories using the Budapest Criteria | 3 months and 12 months | 
| Physical function | Patient reported outcome measure to assess level of function, daily living activities and their affect on pain measured by answering 12 questions using the Oxford Knee Score (OKS) | 3 months and 12 months | 
| Emotional functioning | Patients emotional functioning measured on a scale of 1-5 using the Profile of Mood States (POMS) | 3 months and 12 months | 
| Postoperative cognitive impairment | Assessment of different cognitive domains such as attention, concentration, memory, language, conceptual thinking, calculations, and orientation out of a total score of 22 using Montreal Cognitive Assessment - Blind (MoCA-BLIND) | 3 months | 
| Patient Satisfaction | Assessment of patient satisfaction with surgery on scale of 0-100 | 3 months and 12 months | 
| Quality of life assessment | Patient reported assessment of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression on a scale of level 1 - level 5 using the EuroQol 5-dimension 5-level (EQ-5D-5L) | 3 months and 12 months | 
| Adverse events | Monitored as a secondary safety outcome using an assessment of follow-up visits for drug related adverse events and passive surveillance of clinical notes | 3 months and 12 months |