Perioperative duloxetine to reduce opioid use after knee replacement

Effect of Perioperative Duloxetine Administration on Opioid Consumption Following Total Knee Arthroplasty

This trial will test whether taking 60 mg duloxetine starting two weeks before and continuing after knee replacement helps people with knee osteoarthritis use fewer opioid pain medicines in the first week after surgery.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 150 (estimated)
• Ages: 50 Years and up
• Sex: All
• Sponsor: Sunnybrook Health Sciences Centre (Academic / other)
• Locations: 2 sites (Toronto, Ontario and 1 other locations)
• Trial ID: NCT06423716 on ClinicalTrials.gov

What this trial studies

This randomized, double-blind, placebo-controlled Phase 4 trial will assign adults having elective unilateral total knee arthroplasty to receive either 60 mg duloxetine daily starting two weeks before surgery or matching placebo alongside standard analgesic care. The primary outcome is cumulative opioid consumption over the first postoperative week, and secondary outcomes include nausea/vomiting and discharge readiness. Investigators will collect opioid use and patient-reported outcomes during the perioperative period and follow standardized prescribing and analgesia protocols. The design addresses limitations of earlier trials by using the recommended 60 mg dose and initiating therapy preoperatively for a longer duration.

Who should consider this trial

Good fit: Adults aged 50 or older with knee osteoarthritis scheduled for elective unilateral total knee replacement who do not have contraindications to duloxetine are the intended participants.

Not a fit: Patients on interacting antidepressants or contraindicated medications, or those with severe liver or kidney disease, or undergoing non-elective or bilateral procedures may not be eligible or likely to benefit.

Why it matters

Potential benefit: If successful, this approach could reduce opioid use and opioid-related side effects after knee replacement and ease early recovery.

How similar studies have performed: Previous studies of duloxetine around knee surgery showed small or inconsistent opioid-sparing and pain benefits, often using lower doses or shorter durations, so the preoperative 60 mg approach is less well tested.

Eligibility criteria

Inclusion Criteria:

1. Age \>=50
2. Presence of knee osteoarthritis
3. Planned for elective unilateral total knee arthroplasty
4. ASA I - III
5. 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.

Exclusion Criteria:

1. Lack of patient consent; unlikely to comply with follow-up
2. 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
3. Chronic and high dose opioid use (\&gt;30mg oral morphine equivalent per day)
4. Substance use disorder (cannabis and related products, alcohol use disorder, opioid used disorder, illicit drugs)
5. Uncontrolled hypertension (systolic BP \&gt; 180mmHg)
6. Untreated psychiatric illness (e.g. depression, suicidal ideation, bipolar disorder)
7. Involved in worker's compensation case/law suit (verbally declared by patient)

Where this trial is running

Toronto, Ontario and 1 other locations

• Sunnybrook Health Sciences Centre — Toronto, Ontario, Canada (Recruiting)
• Sunnybrook Health Sciences Centre — Toronto, Ontario, Canada (Recruiting)

Study contacts

• Study coordinator: Howard Meng, MD

Conditions Knee Osteoarthritis; total knee arthroplasty; duloxetine; postoperative pain