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

NCT03880916 | Unknown

• 1 other identifier: KC18MESI0455
• Study Type: interventional
• Target: 80
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Osteoarthritis, Knee

Keywords

Duloxetine

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• Pain Visual Analogue Scale (VAS) score

  Change from baseline VAS score at postoperative 2 days, 1, 2, 6, 12 weeks

• Range of motion of the knee joint

  Change from baseline range of motion at postoperative 2 days, 1, 2, 6, 12 weeks

Study Arms (2)

Duloxetine group

EXPERIMENTAL

1. Phase I (preemptive): 2weeks before operation (30mg for 2weeks) 2. Phase II (maintenance): 6weeks after operation (30mg for 6 weeks) plus routine pain control (celecoxib, pregabalin, acetaminophen/tramadol, oxycodone)

Drug: Duloxetine; Drug: Placebo

Placebo group

PLACEBO COMPARATOR

1. Phase I (preemptive): 2weeks before operation (Placebo for 2weeks) 2. Phase II (maintenance): 6weeks after operation (Placebo for 6 weeks) plus routine pain control (celecoxib, pregabalin, acetaminophen/tramadol, oxycodone)

Drug: Duloxetine; Drug: Placebo

Interventions

Duloxetine DRUG

1. Phase I (preemptive): 2weeks before operation (30mg for 2weeks) 2. Phase II (maintenance): 6weeks after operation (30mg for 6 weeks) plus routine pain control (celecoxib, pregabalin, acetaminophen/tramadol, oxycodone)

Duloxetine group; Placebo group

Placebo DRUG

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)

Duloxetine group; Placebo group

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• The Catholic University of Korea: lead

MeSH Terms

Conditions

Osteoarthritis, Knee

Interventions

Duloxetine Hydrochloride

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 6, 2019
• First Posted: March 19, 2019
• Study Start: March 30, 2019
• Primary Completion: March 31, 2020
• Study Completion: March 31, 2020
• Last Updated: March 19, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share