Duloxetine RCT on Postop TKA Outcomes

Pain, Postoperative Clinical Trial

Official title:

A Prospective, Triple-Blind, Randomized Controlled Trial Evaluating Duloxetine on Post-Operative Outcomes Following Primary Total Knee Arthroplasty in Patients With and Without Central Sensitization

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05086393
• Other study ID #: 19081605
• Status: Recruiting
• Phase: Phase 4
• Start date: November 1, 2021
• Est. completion date: February 1, 2025

Study information

• Verified date: June 2024
• Source: Rush University Medical Center
• Contact: Denis Nam, MD, MSc
• Phone: (312)432-2468
• Email: denis.nam[@]rushortho.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Despite advances in surgical techniques and multimodal analgesia, many patients experience severe pain following total knee arthroplasty (TKA). In addition, chronic osteoarthritis, the most common reason patients undergo arthroplasty, predisposes patients to neuropathic pain with an estimated 23% of osteoarthritic patients suffering from neuropathic pain in addition to their nociceptive pain. This process is believed to lower the pain threshold and may lead to central sensitization, a condition defined as "the increase in the excitability and synaptic efficacy of neurons in the central nociceptive pathways that manifests as pain hypersensitivity." Central sensitization is present in 20% to 40% of patients with advanced knee osteoarthritis and believed to predispose them to increased preoperative and postoperative levels of pain.

In previous studies, duloxetine has been shown to reduce postoperative pain and opioid consumption. In a 2019 randomized controlled trial (RCT), Ko et al. reported that 30 milligrams (mg) of duloxetine administered one day prior to surgery and continued for 6 weeks after surgery decreased pain scores in patients with central sensitization who underwent TKA. Duloxetine administered for a shorter duration of time has also shown beneficial results. In their 2010 study, Ho et al. found that although 60 mg of duloxetine administered prior to surgery and on the first postoperative day did not significantly improve postoperative pain scores, it significantly reduced postoperative inpatient morphine requirements following TKA. Similarly, in a 2016, triple-blinded, randomized, placebo-controlled trial, YaDeau et al. found that 60 mg of duloxetine given for 15 days following surgery did not significantly impact pain scores but did significantly reduce opioid consumption in the two weeks following TKA. Although promising, these previous studies are difficult to interpret as they evaluated different patient populations, used different dosages of duloxetine, and administered for different lengths of time.

To our knowledge, all previous prospective, randomized controlled trials have examined only patients undergoing TKA, either focused only on patients with central sensitization or failed to differentiate between patients with and without central sensitization in their study population, or failed to administer duloxetine for the 4-8 week duration that has been traditionally recommended to assess the efficacy of SNRIs for other clinical indications.

The researchers propose to fill this knowledge gap by conducting a study that evaluates TKA patients, includes and differentiates patients with and without central sensitization, and administers duloxetine for the full recommended trial duration.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 504
• Est. completion date: February 1, 2025
• Est. primary completion date: November 1, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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)

Related Conditions & MeSH terms

• Pain, Postoperative
• Total Knee Arthroplasty

Intervention

Drug:
• Duloxetine
Patients will be randomized to receive Duloxetine or a placebo.
• Placebos
Patients will be randomized to receive Duloxetine or a placebo.

Locations

Country	Name	City	State
United States	Rush University medical Center	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Rush University Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Patient reported outcome: Visual Analogue Scale (VAS) pain score	Using daily VAS pain score, scale of 1 to 10, 10 being the worst	At the 6 week postoperative mark, following TKA
Secondary	Patient reported outcome: Knee injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS,JR)	KOOS,JR outcome assessed at 6 weeks post op from TKA. This is a 0-100 score where 100 represents a perfectly functioning joint.	At the 6 week postoperative mark, following TKA
Secondary	Patient reported outcome: Sleep duration and quality	Post-operative sleep duration and quality assessed daily, number of hours slept	Daily reporting of sleep duration for 2 weeks following TKA
Secondary	Complications	Adverse medication effects after initiating duloxetine	Up to 3 months following surgery