Effect of Duloxetine on Opioid Use After Total Knee Arthroplasty

Effect of Duloxetine on Opioid Use After Total Knee Arthroplasty: A Double-blinded Randomized Control Trial

Post-discharge pain after total knee arthroplasty remains problematic; many patients have excessive pain at the 2 week time point (and often thereafter). Reduction in opioid use has become a national goal, due to the 'epidemic' in opioid misuse.

In addition to enrolling non-opioid users, we will enroll up to 15 chronic opioid users.

Study Overview

• Status: Completed
• Conditions: Pain, Acute; Pain, Chronic; Joint Disease
• Intervention / Treatment: Drug: Cymbalta; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 160
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Hospital For Special Surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 25 to 75 years
• Planned use of regional anesthesia
• Ability to follow study protocol
• English speaking (Primary outcome obtained via telephone call and secondary outcomes include questionnaires validated in English only)
• Patients planning on being discharged home or to a rehabilitation center that has agreed to participate

Exclusion Criteria:

• Current Use of duloxetine or other SNRIs, SSRIs, MAOIs, Tricyclic antidepressants, triptans (sumatriptan, rizatriptan, naratriptan, eletriptan, almotriptan, frovatriptan), lithium, buspirone, St. John's Wort

• Hepatic insufficiency

  o Hepatoxicity is reported as a side effect of duloxetine. "Median time to detection of transaminase elevation was about two months" (package insert 5.2

• Renal insufficiency (ESRD, HD, estimated creatinine clearance < 50 ml/min)

  • Severe CRI may impair duloxetine clearance
  • CLcr=[(140-age (years)] x weight (kg)x0.85 (for female patients)/[72xserum creatinine (mg/dL)]
• Patients younger than 25 years old and older than 75
• Patients intending to receive general anesthesia
• Allergy or intolerance to one of the study medications
• Patients with an ASA of IV
• Chronic gabapentin/pregabalin use (regular use for longer than 3 months)
• Patients with major prior ipsilateral open knee surgery.

• Chronic opioid use (taking opioids for longer than 3 months)

  • However, patients using chronic opioids may enroll in a parallel pilot study entitled 'effect of duloxetine on opioid use after total knee athroplasty among patients exposed to opioids- a pilot study'. The chronic opioid users will be allowed to continue their customary analgesics. The pilot study is otherwise identical to the main study.
  • This study will enroll up to 15 chronic opioid users. After that, all chronic opioid users are excluded.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Duloxetine ("Cymbalta"); Epidural analgesia after knee arthroplasty is not as prevalent at HSS as formerly, in large part due to the rise of local infiltration analgesia. Studies using epidural analgesia may also lack generalizability given the infrequent use of epidural analgesia at other institutions. For these reasons, we plan to use adductor canal nerve blockade + local infiltration analgesia for management of immediate postoperative pain. Patients will receive spinal anesthesia as the primary anesthetic. It is particularly important to study duloxetine ("Cymbalta") in the context of local infiltration analgesia, as patients receiving local infiltration analgesia receive increased doses of opioids, compared to patients receiving epidural analgesia.	Drug: Cymbalta; Duloxetine ("Cymbalta") is a serotonin and norepinephrine dual reuptake inhibitor (SNRI) that is an effective treatment for painful diabetic neuropathy. It is approved for major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathy, fibromyalgia, and chronic musculoskeletal pain
PLACEBO_COMPARATOR: Placebo; Placebo to compare pain scores and opioid use againts Duloxetine	Other: Placebo; Placebo to compare outcomes against Duloxetine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Opioid Use	Opioid use (measured in cumulative morphine equivalents)	Post-operative day 14
Pain Scores	Numerical Rating Score pain with movement. Minimum value of 0, maximum value of 10. Higher scores mean more pain and worse outcome.	Post-operative day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Phenotype	2011 Survey Criteria for Fibromyalgia. Minimum value of 0, and maximum value of 12. A higher score means a worse outcome.	Day of surgery

Collaborators and Investigators

• Sponsor: Hospital for Special Surgery, New York

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 28, 2017
• Primary Completion (ACTUAL): December 3, 2020
• Study Completion (ACTUAL): February 10, 2021

Study Registration Dates

• First Submitted: August 29, 2017
• First Submitted That Met QC Criteria: August 31, 2017
• First Posted (ACTUAL): September 1, 2017

Study Record Updates

• Last Update Posted (ACTUAL): April 26, 2022
• Last Update Submitted That Met QC Criteria: March 29, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Musculoskeletal Diseases; Chronic Pain; Joint Diseases; Acute Pain; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Dopamine Agents; Serotonin and Noradrenaline Reuptake Inhibitors; Duloxetine Hydrochloride
• Other Study ID Numbers: 2017-0655

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes