Pre-emptive Effect of Duloxetine in the Second Knee in Staged Total Knee Arthroplasty

Study Overview
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Brief Summary
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In Korea, the interval between knee arthroplasties is usually 1 week. According to previous studies, when total knee arthroplasty was performed at 1-week intervals, total bleeding was reduced and the period of hospital stay was shortened. However, if stepwise total knee arthroplasty is performed at intervals of one week, the pain is greater after the second operation, and the reason for this phenomenon is known to be due to central sensitization and opioid resistance. Therefore, the investigators aim to confirm whether Duloxetine reduces the central sensitization as previously known and affects the pain control after the second operation.

Detailed Description
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Degenerative arthritis of the knee is one of the most common arthritis. Currently, total knee arthroplasty is the most commonly used surgical procedure. The degenerative changes of the knee are often seen on both sides, and bilateral total knee arthroplasty is usually performed. In the past, bilateral total knee arthroplasty was performed at the same time. When bilateral total knee arthroplasty was performed simultaneously, the complications such as increased mortality occurred. So, it is common to perform bilateral total knee arthroplasty in a stepwise manner. In Korea, the interval between knee arthroplasties is usually 1 week. According to previous studies, when total knee arthroplasty was performed at 1-week intervals, total blood loss was reduced and the period of hospital stay was shortened. However, if stepwise total knee arthroplasty is performed at intervals of one week, the pain is greater after the second operation, and the reason for this phenomenon is known to be due to central sensitization and opioid resistance. Therefore, the investigators aim to 1) whether the pain is greater than the first operation at the second operation in the control group. 2) whether the pre-operative and post-operative duloxetine use causes the pre-analgesic effect on the second operation. 3) whether the central sensitization, clinical score, and painkiller usage are different by comparing duloxetine-treated group and control group.

Official Title
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Pre-emptive Effect of Duloxetine in the Second Knee in Staged Total Knee Arthroplasty: A Randomized Controlled Study

Conditions
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Knee Osteoarthritis

Intervention / Treatment
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* Drug: Duloxetine HCl 30mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Candidate for staged bilateral total knee replacement arthroplasty due to osteoarthritis of the knee. Exclusion Criteria: Known allergic reaction to duloxetine Secondary arthritis (ex. Rheumatic arthritis, traumatic arthritis, septic arthritis) History of major operation(ex. Arthroscopic knee arthroplasty, osteotomy, open reduction, and internal fixation) History of manic or bipolar disorder, epilepsy, increased intraocular pressure or risk of acute angle-closure glaucoma, liver disease, moderate renal disease (CLcr < 30ml/min), severe heart disease, uncontrolled hypertension, unregulated narrow-angle glaucoma Known congenital or acquired coagulopathy Known genetic disorders such as fulminant intolerance / glucose-galactose uptake disorder/sucrose isoleucetase deficiency Taken MAO inhibitor, anti-depressants, diuretics, duloxetine Refuse to participate in the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control<br>Duloxetine HCl 30mg is not used. | Drug: Duloxetine HCl 30mg<br>* In the duloxetine group, one capsule of Duloxetine HCl 30mg (Duroceptol) is taken orally and daily from the day before the first operation to seven days after the second operation. In the control group, the patients can take painkillers except duloxetine.<br>|
| Experimental: Duloxetine<br>One capsule of Duloxetine HCl 30mg (Duroceptol) is taken orally and daily from the day before the first operation to seven days after the second operation. | Drug: Duloxetine HCl 30mg<br>* In the duloxetine group, one capsule of Duloxetine HCl 30mg (Duroceptol) is taken orally and daily from the day before the first operation to seven days after the second operation. In the control group, the patients can take painkillers except duloxetine.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain VAS | Pain VAS(11-point numeric scale: 0-11) at rest, maximal knee flexion and maximal knee extension | day 7 (inpatient) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Central censitization | DN4 (Douleur Neuropathique 4) | Preop. day 1, 2, 7 (inpatient) , Postop. 6 week, 3 month | 
| Opioid consumption | Opioid conversion to Morphine IV | Preop. day 1, 2, 7 (inpatient) , Postop. 6 week, 3 month | 
| Pain VAS | Pain VAS(11-point numeric scale: 0-11) at rest, maximal knee flexion and maximal knee extension | Preop. day 1, 2 (inpatient) , Postop. 6 week, 3 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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total knee replacement arthroplasty, total knee arthroplasty, central censitization, duloxetine, serotonin-norepinephrine reuptake inhibitors, pre-emptive effect