Does Duloxetine Reduce Sub-Acute Pain After Knee Arthroplasty?

We are investigating the impact of duloxetine ("Cymbalta"), a serotonin and norepinephrine reuptake inhibitor, on pain after total knee arthroplasty (TKA). Specifically, the investigators will determine whether duloxetine, 60 mg daily for 2 weeks, reduces pain scores 2 weeks after TKA.

Study Overview

• Status: Completed
• Conditions: Total Knee Arthroplasty
• Intervention / Treatment: Drug: Duloxetine 60mg; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 106
• 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:

• Patients with osteoarthritis scheduled for primary tricompartmental total knee arthroplasty with a participating surgeon
• 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:

• Concurrent use of duloxetine or other SNRIs, MAOIs, Tricyclic antidepressants, triptans (sumatriptan, rizatriptan, naratriptan, zolmitriptan, eletriptan, almotriptan, frovatriptan), lithium, buspirone, St. John's Wort
• Hepatic insufficiency
• Renal insufficiency
• 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)
• Chronic opioid use (taking opioids for longer than 3 months)
• Patients with major prior ipsilateral open knee surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Duloxetine; Patients will receive 60mg of duloxetine per dose. 1 capsule will be taken preoperatively. Starting on postoperative day (POD) 1, patients will take one capsule once a day until end of POD14.	Drug: Duloxetine 60mg; Patients will receive 60mg of duloxetine per dose. 1 capsule will be taken pre-operatively. One capsule once a day until end of POD14.; Other Names: Cymbalta
Placebo Comparator: Control; Patients will receive 0mg of duloxetine	Drug: Placebo; Patients will receive placebo drug with no active ingredients per dose. 1 capsule will be taken pre-operatively. One capsule once a day until end of POD14.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NRS Pain With Ambulation at 2 Weeks	When considering the pain in the knee in which you are having/had surgery, on a scale of 0-10, with 0 being no pain and 10 being pain as bad as you can imagine, how would you describe your level of pain in the last 24 hours during ambulation?	2 weeks after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Daily Opioid Use (mg Oral Morphine Equivalents)	Total daily opioid use (including PO, PCEA, IV, subcutaneous, IV push) in mg oral morphine equivalents on POD 1.	POD 1
Nausea Severity	Nausea severity measured using Likert scale ranging from 0 (none) to 10 (severe).	POD 1

Collaborators and Investigators

• Sponsor: Hospital for Special Surgery, New York

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: December 4, 2013
• First Submitted That Met QC Criteria: December 6, 2013
• First Posted (Estimate): December 9, 2013

Study Record Updates

• Last Update Posted (Actual): August 29, 2017
• Last Update Submitted That Met QC Criteria: July 27, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; 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: 2012-016