Clinical trial NCT03792828: Pre-emptive Effect of Duloxetine in the Second Knee in Staged Total Knee Arthroplasty
Official title: Pre-emptive Effect of Duloxetine in the Second Knee in Staged Total Knee Arthroplasty: A Randomized Controlled Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Knee Osteoarthritis
Keywords: total knee replacement arthroplasty
total knee arthroplasty
central censitization
duloxetine
serotonin-norepinephrine reuptake inhibitors
pre-emptive effect
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
First posted: 2019-01-03
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Pain VAS
timeFrame: day 7 (inpatient)
Secondary outcomes:
measure: Central censitization
timeFrame: Preop. day 1, 2, 7 (inpatient) , Postop. 6 week, 3 month
measure: Opioid consumption
timeFrame: Preop. day 1, 2, 7 (inpatient) , Postop. 6 week, 3 month
measure: Pain VAS
timeFrame: Preop. day 1, 2 (inpatient) , Postop. 6 week, 3 month
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul National University Boramae Medical Center
Study officials:
affiliation: SMG-SNU Boramae Medical Center
name: Seung-Baik Kang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Forster MC, Bauze AJ, Bailie AG, Falworth MS, Oakeshott RD. A retrospective comparative study of bilateral total knee replacement staged at a one-week interval. J Bone Joint Surg Br. 2006 Aug;88(8):1006-10. doi: 10.1302/0301-620X.88B8.17862.
citation: Kim MH, Nahm FS, Kim TK, Chang MJ, Do SH. Comparison of postoperative pain in the first and second knee in staged bilateral total knee arthroplasty: clinical evidence of enhanced pain sensitivity after surgical injury. Pain. 2014 Jan;155(1):22-27. doi: 10.1016/j.pain.2013.08.027. Epub 2013 Aug 30.
citation: YaDeau JT, Brummett CM, Mayman DJ, Lin Y, Goytizolo EA, Padgett DE, Alexiades MM, Kahn RL, Jules-Elysee KM, Fields KG, Goon AK, Gadulov Y, Westrich G. Duloxetine and Subacute Pain after Knee Arthroplasty when Added to a Multimodal Analgesic Regimen: A Randomized, Placebo-controlled, Triple-blinded Trial. Anesthesiology. 2016 Sep;125(3):561-72. doi: 10.1097/ALN.0000000000001228.