Perioperative Vitamin C to Reduce Persistent Pain After Total Knee Arthroplasty

Phase 2

Recruiting

• Conditions: Knee Pain Chronic; Post Operative Pain; Chronic Pain
• Interventions: Drug: Placebo; Drug: Vitamin C

• Registration Number: NCT06123715
• Lead Sponsor: University Health Network, Toronto

Brief Summary

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

PROVISION is a multicentre, pilot, parallel-group, blinded, randomized controlled trial of 300 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.

Study Timeline

• Study First Submitted: 2023-10-10
• Study First Submitted QC: 2023-11-07
• Study First Posted: 2023-11-09
• Study Start: 2024-04-16
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-22
• Last Update Posted: 2025-04-25
• Primary Completion: 2025-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 300

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Preoperative placebo capsules
Intervention	Vitamin C	Preoperative Vitamin C capsules

Primary Outcome Measures

Name	Time	Method
Study will determine feasibility of enrolling, recruiting, and follow-up with patients.	12 months	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.
Resource Assessment	12 months	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.
Clinical site compliance	12 months	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.

Secondary Outcome Measures

Name	Time	Method
Prevalence of persistent pain	3 months and 12 months	Pain intensity measured using 0-10 Numeric Rating Scale (NRS) scale at rest and movement
Qualities and characteristics of persistent pain	3 months and 12 months	Pain qualities measured using the 0-10 scale of the Short Form McGill Pain Questionnaire 2 (SF-MPQ-2)
Persistent Neuropathic Pain	3 months and 12 months	Neuropathic pain assessed on a binary scale of Yes or No using the Douleur Neuropathique 4 (DN4) symptoms interview
Acute and chronic analgesic consumption	Day of surgery, post-operative day 1-3, 3 months, and 12 months	Analgesic and oral morphine-equivalent opioid consumption
Development of Complex Regional Pain Syndrome (CRPS)	3 months and 12 months	Presence of CRPS measured by a physical assessment of sensory, vasomotor, sudomotor/edema, and motor/tropic categories using the Budapest Criteria
Physical function	3 months and 12 months	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)
Emotional functioning	3 months and 12 months	Patients emotional functioning measured on a scale of 1-5 using the EQ-5D-5L
Patient Satisfaction	3 months and 12 months	Assessment of patient satisfaction with surgery on scale of 0-100
Adverse events	3 months and 12 months	Monitored as a secondary safety outcome using an assessment of follow-up visits for drug related adverse events and passive surveillance of clinical notes
Quality of life assessment	3 months and 12 months	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)

Trial Locations

Locations (3)

Sunnybrook - Holland Centre; 🇨🇦 Toronto, Ontario, Canada

Toronto Western Hospital; 🇨🇦 Toronto, Ontario, Canada

Mount Sinai Hospital; 🇨🇦 Toronto, Ontario, Canada