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

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

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.

Study Overview

• Status: Unknown
• Conditions: Knee Osteoarthritis
• Intervention / Treatment: Drug: Duloxetine HCl 30mg

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.

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Seung-Baik Kang, MD, PhD; Phone Number: +82-870-3931; Email: ossbkang@gmail.com
• Study Contact Backup: Name: JoungYoup Shin, MD; Phone Number: +82-10-5310-7133; Email: sjy820828@gmail.com

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 07061
    • Seoul National University Boramae Medical Center
    • Contact: Seung-Baik Kang, MD, PhD; Phone Number: +82-2-870-3931; Email: ossbkang@gmail.com
    • Principal Investigator: Seung-Baik Kang, MD, PhD
    • Principal Investigator: Chong Bum Chang, MD, PhD
    • Principal Investigator: Moon Jong Chang, MD, PhD
    • Principal Investigator: Joung Youp Shin, MD
    • Principal Investigator: Whang Kim, MD
    • Principal Investigator: Dong Whan Suh, MD
    • Principal Investigator: Jong Byung Oh, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control; Duloxetine HCl 30mg is not used.	Drug: Duloxetine HCl 30mg; 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.
Experimental: Duloxetine; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Investigators: Principal Investigator: Seung-Baik Kang, MD, PhD, SMG-SNU Boramae Medical Center

Publications and helpful links

General Publications

• Shin HJ, Kim EY, Na HS, Kim TK, Kim MH, Do SH. Magnesium sulphate attenuates acute postoperative pain and increased pain intensity after surgical injury in staged bilateral total knee arthroplasty: a randomized, double-blinded, placebo-controlled trial. Br J Anaesth. 2016 Oct;117(4):497-503. doi: 10.1093/bja/aew227. Epub 2016 Oct 17.
• Onutu AH. Duloxetine, an antidepressant with analgesic properties - a preliminary analysis. Rom J Anaesth Intensive Care. 2015 Oct;22(2):123-128.
• Scott CE, Murray RC, MacDonald DJ, Biant LC. Staged bilateral total knee replacement: changes in expectations and outcomes between the first and second operations. Bone Joint J. 2014 Jun;96-B(6):752-8. doi: 10.1302/0301-620X.96B6.32793.
• Hussain N, Chien T, Hussain F, Bookwala A, Simunovic N, Shetty V, Bhandari M. Simultaneous versus staged bilateral total knee arthroplasty: a meta-analysis evaluating mortality, peri-operative complications and infection rates. HSS J. 2013 Feb;9(1):50-9. doi: 10.1007/s11420-012-9315-7. Epub 2013 Jan 24.
• Sun J, Li L, Yuan S, Zhou Y. Analysis of Early Postoperative Pain in the First and Second Knee in Staged Bilateral Total Knee Arthroplasty: A Retrospective Controlled Study. PLoS One. 2015 Jun 11;10(6):e0129973. doi: 10.1371/journal.pone.0129973. eCollection 2015.
• Kumar V, Bin Abd Razak HR, Chong HC, Tan AH. Functional Outcomes of the Second Surgery Are Similar to the First in Asians Undergoing Staged-Bilateral Total Knee Arthroplasty. Ann Acad Med Singap. 2015 Nov;44(11):514-8.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2019
• Primary Completion (Anticipated): October 1, 2019
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: November 28, 2018
• First Submitted That Met QC Criteria: January 1, 2019
• First Posted (Actual): January 3, 2019

Study Record Updates

• Last Update Posted (Actual): January 3, 2019
• Last Update Submitted That Met QC Criteria: January 1, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: total knee arthroplasty; duloxetine; total knee replacement arthroplasty; serotonin-norepinephrine reuptake inhibitors; central censitization; pre-emptive effect
• 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: SNUBMC_20181128

Drug and device information, study documents

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