Effect of peRiopErative duLoxetIne Administration on Opioid Consumption Following Total kneE Arthroplasty (RELIFE)

NCT06423716 | Recruiting Phase 4

• 1 other identifier: SBK 6156
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 2

Brief Summary

Knee replacement surgery for osteoarthritis is a commonly performed procedure in Canada with 75,000 of these surgeries performed each year. Success rate for knee replacement surgery is high but more than 20% of patients are still dissatisfied mainly due to reports of ongoing pain. Pain control following knee surgery is important in order to allow patients to engage in recovery and rehabilitation. The current standard of pain management after surgery centers around the use of opioids which is a concerning practice as highlighted by the opioid epidemic. Duloxetine is an antidepressant that has pain relieving properties and it has been studied in patients undergoing knee replacement surgery. Studies to date have not been designed optimally to demonstrate the full effects of opioid dose reduction and the use of duloxetine as a medication following knee replacement surgery. This research study seeks to start duloxetine before surgery, at the recommended therapeutic dose, and for the duration of the early rehabilitation period. If the study is successful, this low-cost medication can improve satisfaction rates and change the standard way the pain management is typically carried out for patients undergoing the knee replacement surgery.

Conditions

Knee Osteoarthritis

Keywords

total knee arthroplasty; duloxetine; postoperative pain

Outcome Measures

Primary Outcomes (1)

• Opioid consumption

  Cumulative opioid consumption at 1 week post-operatively

  Cumulative opioid consumption at 1 week post-operatively

Secondary Outcomes (14)

• Nausea/vomiting

  12 weeks (i.e., duration of study)

• Pain at rest and with activity

  10-14 days preoperative; 1,6,12 weeks and 4.5 months

• Additional analgesic use

  8 weeks (i.e., duration of study)

• Additional analgesic use: opioid prescription

  8 weeks (i.e., duration of study)

• Physical function measured by BPI

  Preoperative, 6, 12 weeks and 4.5 months

Study Arms (2)

Intervention

EXPERIMENTAL

Duloxetine 60mg OD for 2 weeks preoperatively then 60mg OD for 6 weeks post-surgery.

Drug: Duloxetine

Control

PLACEBO COMPARATOR

Placebo OD for 2 weeks preoperatively then OD for 6 weeks post-surgery.

Drug: Placebo

Interventions

Duloxetine DRUG

60mg duloxetine given 2 weeks prior to total knee arthroplasty and continued for 6 weeks after surgery.

Intervention

Placebo DRUG

Placebo given 2 weeks prior to total knee arthroplasty and continued for 6 weeks after surgery.

Control

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>=50
• Presence of knee osteoarthritis
• Planned for elective unilateral total knee arthroplasty
• ASA I - III
• Baseline creatinine clearance (CrCl) ≥ 30 mL/min within 60 days prior to enrolment, if available. If not available, verbal report from patient of no known renal disease.

You may not qualify if:

• Lack of patient consent; unlikely to comply with follow-up
• Presence of contraindications to study drug use:
• Known hypersensitivity to the drug or components of the product
• Known liver disease - history of cirrhosis, non-alcoholic steatohepatitis
• Uncontrolled narrow - angle glaucoma
• Severe renal impairment (CrCl\<30mL/min)
• Concurrent use of thioridazine
• Concurrent use of potent CYP1A2 inhibitors (e.g. fluvoxamine) and some quinolone antibiotics (e.g. ciprofloxacin or enoxacin)
• Concurrent use of antidepressants (e.g. MAOI, SSRI, SNRI, TCA, St. John's Wort, buspirone)
• Concurrent use of triptan or lithium
• Chronic and high dose opioid use (\&gt;30mg oral morphine equivalent per day)
• Substance use disorder (cannabis and related products, alcohol use disorder, opioid used disorder, illicit drugs)
• Uncontrolled hypertension (systolic BP \&gt; 180mmHg)
• Untreated psychiatric illness (e.g. depression, suicidal ideation, bipolar disorder)
• Involved in worker's compensation case/law suit (verbally declared by patient)

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead

Study Sites (2)

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

RECRUITING

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

RECRUITING

MeSH Terms

Conditions

Osteoarthritis, Knee; Pain, Postoperative

Interventions

Duloxetine Hydrochloride

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Howard Meng, MD

CONTACT

416-480-4864; howard.meng@sunnybrook.ca

Stephen Choi

CONTACT

416-480 -4864; stephen.choi@sunnybrook.ca

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Group 1: Intervention Duloxetine 60mg OD for 2 weeks preoperatively then 60mg OD for 6 weeks post-surgery. Group 2: Control Placebo OD for 2 weeks preoperatively then OD for 6 weeks post-surgery.

Study Record Dates

• First Submitted: May 16, 2024
• First Posted: May 21, 2024
• Study Start: November 1, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: December 19, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Upon publication, no limit on time
• Access Criteria: Contact study investigators

Locations

CA (2)