Effects of Duloxetine on Postoperative Wound Complication of Total Knee Arthroplasty (TKA) in Central Sensitization Patients

Effects of Duloxetine on Postoperative Wound Complication of Total Knee Arthroplasty(TKA) in Central Sensitization Patient

Postoperative wound complications such as wound dehiscence, skin necrosis, persistent wound drainage, delayed healing, and superficial skin infection could have devastating consequences, leading to arthroplasty failure and patient morbidity requiring additional operations and prolonging hospitalization with substantial burden in cost of care. Recently, interest and research on central sensitization (CS) have been increasing. CS is closely correlated with excessive pain. It has two main characteristics: allodynia and hyperalgesia. CS is an abnormal and intense enhancement of pain mechanism by the central nervous system. One of the mechanisms by which this excessive pain occurs in CS is reduced activation of descending inhibitory pathway associated with deficiency in pathways primarily in response to serotonin and norepinephrine. Serotonin plays an important role in normal wound healing by affecting the formation of neovascularization, inflammatory reactions, fibroblasts and tissue proliferation essential for wound healing. Norepinephrine is also closely related to wound healing by controlling chemotaxis of macrophage essential for normal wound healing. CS is a risk factor for the development of postoperative wound complication after primary Total Knee Arthroplasty (TKA). Preclinical models of central sensitization suggest that duloxetine is effective in the treatment. Investigators will compare the wound complication following TKA of central sensitization patients in duloxetine group (n=40) with those in non-duloxetine group (n=40). Investigators will classify the central sensitization patients by central sensitization inventory and divide the central sensitization patients in to 2 groups (duloxetine and non-duloxetine group) randomly. Investigators checks the wound complication after primary TKA and visual assessment scale at preoperative, postoperative 2 days and 1, 2,6,12 weeks. All participants will receive postoperative pain control after TKA using the same pain control regimen and wound dressing regimen except duloxetine.

Study Overview

• Status: Unknown
• Conditions: Osteoarthritis, Knee
• Intervention / Treatment: Drug: Duloxetine; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients for total knee arthroplasty
• having medicare insurance
• Central sensitization inventory (CSI)> 40 (Central sensitization patient )

Exclusion Criteria:

• Rheumatoid arthritis
• Other inflammatory arthritis
• Neuropsychiatric patients
• Allergy or intolerance to study medications
• Patients with an American society of anesthesiologist (ASA) classification of IV (angina, congestive heart failure, dementia, cerebrovascular accident)
• Chronic gabapentin or pregabalin use (regular use for longer than 3 months)
• Chronic opioid use (taking opioids for longer than 3 months)
• Alcohol, drug abuser
• Narcotics addiction

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 group; Phase I (preemptive): 2weeks before operation (30mg for 2weeks); Phase II (maintenance): 6weeks after operation (30mg for 6 weeks) plus routine pain control (celecoxib, pregabalin, acetaminophen/tramadol, oxycodone)	Drug: Duloxetine; Phase I (preemptive): 2weeks before operation (30mg for 2weeks); Phase II (maintenance): 6weeks after operation (30mg for 6 weeks) plus routine pain control (celecoxib, pregabalin, acetaminophen/tramadol, oxycodone); Drug: Placebo; Phase I (preemptive): 2weeks before operation (Placebo for 2weeks) Phase II (maintenance): 6weeks after operation (Placebo for 6 weeks) plus routine pain control (celecoxib, pregabalin, acetaminophen/tramadol, oxycodone)
Placebo Comparator: Placebo group; Phase I (preemptive): 2weeks before operation (Placebo for 2weeks); Phase II (maintenance): 6weeks after operation (Placebo for 6 weeks) plus routine pain control (celecoxib, pregabalin, acetaminophen/tramadol, oxycodone)	Drug: Duloxetine; Phase I (preemptive): 2weeks before operation (30mg for 2weeks); Phase II (maintenance): 6weeks after operation (30mg for 6 weeks) plus routine pain control (celecoxib, pregabalin, acetaminophen/tramadol, oxycodone); Drug: Placebo; Phase I (preemptive): 2weeks before operation (Placebo for 2weeks) Phase II (maintenance): 6weeks after operation (Placebo for 6 weeks) plus routine pain control (celecoxib, pregabalin, acetaminophen/tramadol, oxycodone)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The rates of wound complication	wound dehiscence, suture granuloma, prolonged wound ooze occurring after postoperative day 5, significant hematoma formation, or surgical site infection recorded. Post-operative additional interventions included delayed discharge from hospital due to wound problem, additional outpatient clinic visits to examine the surgical wound, local application of antibiotic ointment, superficial wound debridement or suturing in the office, hematoma aspiration, prescription of antibiotics, or reoperation.	Change from baseline wound complication at postoperative 2 days, 1 week, 2 weeks, 6 weeks, 12 weeks
Hormone level	Cortisol, Serotonin, Norepinephrine related with Central Sensitization and wound healing	Change from baseline hormone level at postoperative 2, 6, 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Visual Analogue Scale (VAS) score	Pain evaluation, It will be measured on a scale of 10 points. Minimum point is 0 and maximum point is 10. Higher values represent a worse outcome.	Change from baseline VAS score at postoperative 2 days, 1, 2, 6, 12 weeks
Range of motion of the knee joint	Range of motion	Change from baseline range of motion at postoperative 2 days, 1, 2, 6, 12 weeks

Collaborators and Investigators

• Sponsor: The Catholic University of Korea

Study record dates

Study Major Dates

• Study Start (Anticipated): March 30, 2019
• Primary Completion (Anticipated): March 31, 2020
• Study Completion (Anticipated): March 31, 2020

Study Registration Dates

• First Submitted: March 6, 2019
• First Submitted That Met QC Criteria: March 18, 2019
• First Posted (Actual): March 19, 2019

Study Record Updates

• Last Update Posted (Actual): March 19, 2019
• Last Update Submitted That Met QC Criteria: March 18, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Duloxetine
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; 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: KC18MESI0455

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No