Duloxetine RCT on Postop TKA Outcomes

NCT05086393 | Completed Phase 4 FDA Drug

• 1 other identifier: 19081605
• Study Type: interventional
• Target: 241
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to determine if duloxetine is associated with differences in post-operative pain, patient-reported outcome measures, and opioid consumption in patients undergoing primary total knee arthroplasty compared to patients who do not receive the medication. If so, duloxetine has the potential to become widely incorporated into the multi-modal analgesic regimen given to patients following knee replacements.

Conditions

Pain, Postoperative; Total Knee Arthroplasty

Keywords

duloxetine

Outcome Measures

Primary Outcomes (1)

• Cumulative opioid consumption at post op day 14 (POD14)

  Measuring in morphine equivalents, collect daily data on opioid consumption for each participant

  Daily reporting of opioid consumption for 2 weeks following TKA

Secondary Outcomes (4)

• Patient reported outcome: Visual Analogue Scale (VAS) pain score

  At the 6 week postoperative mark, following TKA

• Patient reported outcome: Knee injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS,JR)

  At the 6 week postoperative mark, following TKA

• Patient reported outcome: Sleep duration and quality

  Daily reporting of sleep duration for 2 weeks following TKA

• Complications

  Up to 3 months following surgery

Study Arms (2)

Duloxetine

EXPERIMENTAL

Patients randomized to the experimental arm of the study will receive 30 mg of duloxetine and will be advised to consume the medication orally (per os \[PO\]) daily starting one week prior to surgery and to continue until 6 weeks following surgery. The dose of 30 mg was selected as that has been used as that is the largest starting dose used in other RCTs without requiring a preceding adjustment period at a lower dosage.

Drug: Duloxetine

Control

PLACEBO COMPARATOR

Patients randomized to the control arm will receive PO-matched placebo tablets and advised to consume their medication similar to the treatment arm. Both groups of patients will receive their medications from the pharmacy at Rush Medical Center, which will be responsible for providing patients with the appropriate regimen. All patients will receive the same postoperative multimodal analgesic regimen that is normally administered as part of conventional care to patients undergoing TKA at Rush University Medical Center.

Drug: Placebos

Interventions

Duloxetine DRUG

Patients will be randomized to receive Duloxetine or a placebo.

Duloxetine

Placebos DRUG

Patients will be randomized to receive Duloxetine or a placebo.

Control

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Any patient undergoing primary total knee arthroplasty for osteoarthritis
• Age ≥ 18 years old
• Willingness to undergo randomization and return for all scheduled visits
• English speaking

You may not qualify if:

• Age \> 80 years old
• American Society of Anesthesiologists (ASA) Score ≥ 4
• Prior use of SSRIs or SNRIs
• Use of serotonergic drugs in the past 6 months with the exception of tramadol
• Known psychiatric disorder (specifically: generalized anxiety disorder, major depressive disorder, type I or type II bipolar disorder, and schizophrenia)
• Heavy alcohol consumption defined as ≥ 14 drinks per week for men and ≥ 7 drinks per week for women
• Opioid tolerant patients defined as ≥ 60 morphine equivalents (MEQs) per day within 90 days prior to surgery
• Renal impairment defined as a glomerular filtration rate (GFR) \< 30 mL/minute or creatinine \>1.3 mg/dL
• Non-English speaking
• Non-independent (i.e. requires a caretaker to make medical decisions on their behalf)

Sponsors & Collaborators

• Rush University Medical Center: lead

Study Sites (1)

Rush University medical Center

Chicago, Illinois, 60612, United States

Location

MeSH Terms

Conditions

Pain, Postoperative

Interventions

Duloxetine Hydrochloride

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: This study will be triple-blind, thus, the patients, clinicians, and study members involved will be unaware of patient allocation during this study. After the patient completes his or her Central Sensitization Inventory, a study coordinator will grade the survey to determine if the patient should be allocated to the groups with central sensitization or without. Each patient will receive a study ID based on his or her group (detailed in Section XIV). A computer randomization system will be used to allocate patients to receive either duloxetine or a placebo based on their study ID. Only members of the Rush pharmacy staff will possess the list matching the study ID to the study group assignment, ensuring that the study remains triple-blinded and that study coordinators are unaware of a patient's assignment when he or she picks up the study medication from the pharmacy.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Orthopedic Surgery

Model Details: Patients randomized to the experimental arm of the study will receive 30 mg of duloxetine and will be advised to consume the medication orally daily starting one week prior to surgery and to continue until 6 weeks following surgery. The dose of 30 mg was selected as that has been used as that is the largest starting dose used in other RCTs without requiring a preceding adjustment period at a lower dosage. Patients randomized to the control arm will receive placebo tablets and advised to consume their medication similar to the treatment arm. Both groups of patients will receive their medications from the pharmacy at Rush Medical Center, which will be responsible for providing patients with the appropriate regimen. All patients will receive the same postoperative multimodal analgesic regimen that is normally administered as part of conventional care to patients undergoing THA and TKA at Rush University Medical Center.

Study Record Dates

• First Submitted: September 10, 2019
• First Posted: October 20, 2021
• Study Start: November 1, 2021
• Primary Completion: June 1, 2025
• Study Completion: July 23, 2025
• Last Updated: November 14, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)