Effect of Duloxetine on Opioid Use After Total Knee Arthroplasty

NCT03271151 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 2017-0655
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• Pain Phenotype

  Day of surgery

Study Arms (2)

Duloxetine ("Cymbalta")

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

Placebo to compare pain scores and opioid use againts Duloxetine

Other: Placebo

Interventions

Cymbalta 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

Duloxetine ("Cymbalta")

Placebo OTHER

Placebo to compare outcomes against Duloxetine

Placebo

Eligibility Criteria

• Age: 25 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hospital for Special Surgery, New York: lead

Study Sites (1)

Hospital for Special Surgery

New York, New York, 10021, United States

Location

MeSH Terms

Conditions

Joint Diseases; Acute Pain; Chronic Pain

Interventions

Duloxetine Hydrochloride

Condition Hierarchy (Ancestors)

Musculoskeletal Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Jacques Yadeau
• Organization: Anesthesiology Critical Care & Pain Management

Yadeauj@hss.edu

2127742224

Study Officials

• Jacques T YaDeau, MD, Phd

  Hospital for Special Surgery, New York

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2017
• First Posted: September 1, 2017
• Study Start: September 28, 2017
• Primary Completion: December 3, 2020
• Study Completion: February 19, 2021
• Last Updated: December 27, 2024
• Results First Posted: April 26, 2022

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)