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Duloxetine RCT on Postop TKA Outcomes

Primary Purpose

Pain, Postoperative, Total Knee Arthroplasty

Status
Recruiting
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Duloxetine
Placebos
Sponsored by
Rush University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pain, Postoperative focused on measuring duloxetine

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Any patient undergoing primary total knee arthroplasty for osteoarthritis
  • Age ≥ 18 years old
  • Willingness to undergo randomization and return for all scheduled visits
  • English speaking

Exclusion Criteria:

  • Age > 80 years old
  • American Society of Anesthesiologists (ASA) Score ≥ 4
  • Prior use of SSRIs or SNRIs
  • Use of serotonergic drugs in the past 6 months with the exception of tramadol
  • Known psychiatric disorder (specifically: generalized anxiety disorder, major depressive disorder, type I or type II bipolar disorder, and schizophrenia)
  • Heavy alcohol consumption defined as ≥ 14 drinks per week for men and ≥ 7 drinks per week for women
  • Opioid tolerant patients defined as ≥ 60 morphine equivalents (MEQs) per day within 90 days prior to surgery
  • Renal impairment defined as a glomerular filtration rate (GFR) < 30 mL/minute or creatinine >1.3 mg/dL
  • Non-English speaking
  • Non-independent (i.e. requires a caretaker to make medical decisions on their behalf)

Sites / Locations

  • Rush University medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Duloxetine

Control

Arm Description

Patients randomized to the experimental arm of the study will receive 30 mg of duloxetine and will be advised to consume the medication orally (per os [PO]) daily starting one week prior to surgery and to continue until 6 weeks following surgery. The dose of 30 mg was selected as that has been used as that is the largest starting dose used in other RCTs without requiring a preceding adjustment period at a lower dosage.

Patients randomized to the control arm will receive PO-matched placebo tablets and advised to consume their medication similar to the treatment arm. Both groups of patients will receive their medications from the pharmacy at Rush Medical Center, which will be responsible for providing patients with the appropriate regimen. All patients will receive the same postoperative multimodal analgesic regimen that is normally administered as part of conventional care to patients undergoing TKA at Rush University Medical Center.

Outcomes

Primary Outcome Measures

Cumulative opioid consumption at post op day 14 (POD14)
Measuring in morphine equivalents, collect daily data on opioid consumption for each participant

Secondary Outcome Measures

Patient reported outcome: Visual Analogue Scale (VAS) pain score
Using daily VAS pain score, scale of 1 to 10, 10 being the worst
Patient reported outcome: Knee injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS,JR)
KOOS,JR outcome assessed at 6 weeks post op from TKA. This is a 0-100 score where 100 represents a perfectly functioning joint.
Patient reported outcome: Sleep duration and quality
Post-operative sleep duration and quality assessed daily, number of hours slept
Complications
Adverse medication effects after initiating duloxetine

Full Information

First Posted
September 10, 2019
Last Updated
January 25, 2023
Sponsor
Rush University Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT05086393
Brief Title
Duloxetine RCT on Postop TKA Outcomes
Official Title
A Prospective, Triple-Blind, Randomized Controlled Trial Evaluating Duloxetine on Post-Operative Outcomes Following Primary Total Knee Arthroplasty in Patients With and Without Central Sensitization
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 1, 2021 (Actual)
Primary Completion Date
November 1, 2023 (Anticipated)
Study Completion Date
May 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Rush University Medical Center

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
Data Monitoring Committee
No

5. Study Description

Brief Summary
The aim of this study is to determine if duloxetine is associated with differences in post-operative pain, patient-reported outcome measures, and opioid consumption in patients undergoing primary total knee arthroplasty compared to patients who do not receive the medication. If so, duloxetine has the potential to become widely incorporated into the multi-modal analgesic regimen given to patients following knee replacements.
Detailed Description
Despite advances in surgical techniques and multimodal analgesia, many patients experience severe pain following total knee arthroplasty (TKA). In addition, chronic osteoarthritis, the most common reason patients undergo arthroplasty, predisposes patients to neuropathic pain with an estimated 23% of osteoarthritic patients suffering from neuropathic pain in addition to their nociceptive pain. This process is believed to lower the pain threshold and may lead to central sensitization, a condition defined as "the increase in the excitability and synaptic efficacy of neurons in the central nociceptive pathways that manifests as pain hypersensitivity." Central sensitization is present in 20% to 40% of patients with advanced knee osteoarthritis and believed to predispose them to increased preoperative and postoperative levels of pain. In previous studies, duloxetine has been shown to reduce postoperative pain and opioid consumption. In a 2019 randomized controlled trial (RCT), Ko et al. reported that 30 milligrams (mg) of duloxetine administered one day prior to surgery and continued for 6 weeks after surgery decreased pain scores in patients with central sensitization who underwent TKA. Duloxetine administered for a shorter duration of time has also shown beneficial results. In their 2010 study, Ho et al. found that although 60 mg of duloxetine administered prior to surgery and on the first postoperative day did not significantly improve postoperative pain scores, it significantly reduced postoperative inpatient morphine requirements following TKA. Similarly, in a 2016, triple-blinded, randomized, placebo-controlled trial, YaDeau et al. found that 60 mg of duloxetine given for 15 days following surgery did not significantly impact pain scores but did significantly reduce opioid consumption in the two weeks following TKA. Although promising, these previous studies are difficult to interpret as they evaluated different patient populations, used different dosages of duloxetine, and administered for different lengths of time. To our knowledge, all previous prospective, randomized controlled trials have examined only patients undergoing TKA, either focused only on patients with central sensitization or failed to differentiate between patients with and without central sensitization in their study population, or failed to administer duloxetine for the 4-8 week duration that has been traditionally recommended to assess the efficacy of SNRIs for other clinical indications. The researchers propose to fill this knowledge gap by conducting a study that evaluates TKA patients, includes and differentiates patients with and without central sensitization, and administers duloxetine for the full recommended trial duration.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pain, Postoperative, Total Knee Arthroplasty
Keywords
duloxetine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Patients randomized to the experimental arm of the study will receive 30 mg of duloxetine and will be advised to consume the medication orally daily starting one week prior to surgery and to continue until 6 weeks following surgery. The dose of 30 mg was selected as that has been used as that is the largest starting dose used in other RCTs without requiring a preceding adjustment period at a lower dosage. Patients randomized to the control arm will receive placebo tablets and advised to consume their medication similar to the treatment arm. Both groups of patients will receive their medications from the pharmacy at Rush Medical Center, which will be responsible for providing patients with the appropriate regimen. All patients will receive the same postoperative multimodal analgesic regimen that is normally administered as part of conventional care to patients undergoing THA and TKA at Rush University Medical Center.
Masking
ParticipantCare ProviderInvestigator
Masking Description
This study will be triple-blind, thus, the patients, clinicians, and study members involved will be unaware of patient allocation during this study. After the patient completes his or her Central Sensitization Inventory, a study coordinator will grade the survey to determine if the patient should be allocated to the groups with central sensitization or without. Each patient will receive a study ID based on his or her group (detailed in Section XIV). A computer randomization system will be used to allocate patients to receive either duloxetine or a placebo based on their study ID. Only members of the Rush pharmacy staff will possess the list matching the study ID to the study group assignment, ensuring that the study remains triple-blinded and that study coordinators are unaware of a patient's assignment when he or she picks up the study medication from the pharmacy.
Allocation
Randomized
Enrollment
504 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Duloxetine
Arm Type
Experimental
Arm Description
Patients randomized to the experimental arm of the study will receive 30 mg of duloxetine and will be advised to consume the medication orally (per os [PO]) daily starting one week prior to surgery and to continue until 6 weeks following surgery. The dose of 30 mg was selected as that has been used as that is the largest starting dose used in other RCTs without requiring a preceding adjustment period at a lower dosage.
Arm Title
Control
Arm Type
Placebo Comparator
Arm Description
Patients randomized to the control arm will receive PO-matched placebo tablets and advised to consume their medication similar to the treatment arm. Both groups of patients will receive their medications from the pharmacy at Rush Medical Center, which will be responsible for providing patients with the appropriate regimen. All patients will receive the same postoperative multimodal analgesic regimen that is normally administered as part of conventional care to patients undergoing TKA at Rush University Medical Center.
Intervention Type
Drug
Intervention Name(s)
Duloxetine
Intervention Description
Patients will be randomized to receive Duloxetine or a placebo.
Intervention Type
Drug
Intervention Name(s)
Placebos
Intervention Description
Patients will be randomized to receive Duloxetine or a placebo.
Primary Outcome Measure Information:
Title
Cumulative opioid consumption at post op day 14 (POD14)
Description
Measuring in morphine equivalents, collect daily data on opioid consumption for each participant
Time Frame
Daily reporting of opioid consumption for 2 weeks following TKA
Secondary Outcome Measure Information:
Title
Patient reported outcome: Visual Analogue Scale (VAS) pain score
Description
Using daily VAS pain score, scale of 1 to 10, 10 being the worst
Time Frame
At the 6 week postoperative mark, following TKA
Title
Patient reported outcome: Knee injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS,JR)
Description
KOOS,JR outcome assessed at 6 weeks post op from TKA. This is a 0-100 score where 100 represents a perfectly functioning joint.
Time Frame
At the 6 week postoperative mark, following TKA
Title
Patient reported outcome: Sleep duration and quality
Description
Post-operative sleep duration and quality assessed daily, number of hours slept
Time Frame
Daily reporting of sleep duration for 2 weeks following TKA
Title
Complications
Description
Adverse medication effects after initiating duloxetine
Time Frame
Up to 3 months following surgery

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Any patient undergoing primary total knee arthroplasty for osteoarthritis Age ≥ 18 years old Willingness to undergo randomization and return for all scheduled visits English speaking Exclusion Criteria: Age > 80 years old American Society of Anesthesiologists (ASA) Score ≥ 4 Prior use of SSRIs or SNRIs Use of serotonergic drugs in the past 6 months with the exception of tramadol Known psychiatric disorder (specifically: generalized anxiety disorder, major depressive disorder, type I or type II bipolar disorder, and schizophrenia) Heavy alcohol consumption defined as ≥ 14 drinks per week for men and ≥ 7 drinks per week for women Opioid tolerant patients defined as ≥ 60 morphine equivalents (MEQs) per day within 90 days prior to surgery Renal impairment defined as a glomerular filtration rate (GFR) < 30 mL/minute or creatinine >1.3 mg/dL Non-English speaking Non-independent (i.e. requires a caretaker to make medical decisions on their behalf)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Denis Nam, MD, MSc
Phone
(312)432-2468
Email
denis.nam@rushortho.com
First Name & Middle Initial & Last Name or Official Title & Degree
Anne DeBenedetti, BA
Phone
(312)432-2468
Email
anne.debenedetti@rushortho.com
Facility Information:
Facility Name
Rush University medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anne DeBenedetti, BA
Phone
312-432-2468
Email
anne.debenedetti@rushortho.com
First Name & Middle Initial & Last Name & Degree
Craig Della Valle, MD
First Name & Middle Initial & Last Name & Degree
Vasili Karas, MD

12. IPD Sharing Statement

Plan to Share IPD
No

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Duloxetine RCT on Postop TKA Outcomes

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