Effect of Duloxetine on Opioid Use After Total Knee Arthroplasty

NCT ID: NCT03271151

Last Updated: 2024-12-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-28
• Study Completion Date: 2021-02-19

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.

Conditions

Joint Disease; Pain, Acute; Pain, Chronic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Cymbalta

Intervention Type: DRUG

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

Placebo to compare pain scores and opioid use againts Duloxetine

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo to compare outcomes against Duloxetine

Interventions

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

Intervention Type: DRUG

Placebo

Placebo to compare outcomes against Duloxetine

Intervention Type: OTHER

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.

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospital for Special Surgery, New York

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jacques T YaDeau, MD, Phd

Role: PRINCIPAL_INVESTIGATOR

Hospital for Special Surgery, New York

Locations

Hospital for Special Surgery

New York, New York, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2017-0655

Identifier Type: -

Identifier Source: org_study_id