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Effect of Duloxetine on Opioid Use After Total Knee Arthroplasty

Primary Purpose

Joint Disease, Pain, Acute, Pain, Chronic

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Cymbalta
Placebo
Sponsored by
Hospital for Special Surgery, New York
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Joint Disease

Eligibility Criteria

25 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Hospital for Special Surgery

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Duloxetine ("Cymbalta")

Placebo

Arm Description

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.

Placebo to compare pain scores and opioid use againts Duloxetine

Outcomes

Primary Outcome Measures

Opioid Use
Opioid use (measured in cumulative morphine equivalents)
Pain Scores
Numerical Rating Score pain with movement. Minimum value of 0, maximum value of 10. Higher scores mean more pain and worse outcome.

Secondary Outcome Measures

Pain Phenotype
2011 Survey Criteria for Fibromyalgia. Minimum value of 0, and maximum value of 12. A higher score means a worse outcome.

Full Information

First Posted
August 29, 2017
Last Updated
March 29, 2022
Sponsor
Hospital for Special Surgery, New York
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1. Study Identification

Unique Protocol Identification Number
NCT03271151
Brief Title
Effect of Duloxetine on Opioid Use After Total Knee Arthroplasty
Official Title
Effect of Duloxetine on Opioid Use After Total Knee Arthroplasty: A Double-blinded Randomized Control Trial
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
September 28, 2017 (Actual)
Primary Completion Date
December 3, 2020 (Actual)
Study Completion Date
February 10, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospital for Special Surgery, New York

4. Oversight

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

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Joint Disease, Pain, Acute, Pain, Chronic

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
160 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Duloxetine ("Cymbalta")
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo to compare pain scores and opioid use againts Duloxetine
Intervention Type
Drug
Intervention Name(s)
Cymbalta
Intervention Description
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
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo to compare outcomes against Duloxetine
Primary Outcome Measure Information:
Title
Opioid Use
Description
Opioid use (measured in cumulative morphine equivalents)
Time Frame
Post-operative day 14
Title
Pain Scores
Description
Numerical Rating Score pain with movement. Minimum value of 0, maximum value of 10. Higher scores mean more pain and worse outcome.
Time Frame
Post-operative day 14
Secondary Outcome Measure Information:
Title
Pain Phenotype
Description
2011 Survey Criteria for Fibromyalgia. Minimum value of 0, and maximum value of 12. A higher score means a worse outcome.
Time Frame
Day of surgery

10. Eligibility

Sex
All
Minimum Age & Unit of Time
25 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jacques T YaDeau, MD, Phd
Organizational Affiliation
Hospital for Special Surgery, New York
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital for Special Surgery
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Effect of Duloxetine on Opioid Use After Total Knee Arthroplasty

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