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

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ClinicalTrials.gov Identifier: NCT03792828

Recruitment Status : Unknown

Verified January 2019 by Seung-Baik Kang, Seoul National University Hospital.
Recruitment status was: Not yet recruiting

First Posted : January 3, 2019

Last Update Posted : January 3, 2019

Sponsor:

Information provided by (Responsible Party):

Seung-Baik Kang, Seoul National University Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Knee Osteoarthritis	Drug: Duloxetine HCl 30mg	Phase 4

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 Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	90 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Single (Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	Pre-emptive Effect of Duloxetine in the Second Knee in Staged Total Knee Arthroplasty: A Randomized Controlled Study
Estimated Study Start Date :	January 2019
Estimated Primary Completion Date :	October 2019
Estimated Study Completion Date :	December 2019

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Osteoarthritis

MedlinePlus related topics: Knee Replacement

Drug Information available for: Duloxetine Duloxetine hydrochloride

U.S. FDA Resources

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 100 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03792828

Contacts

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Contact: Seung-Baik Kang, MD, PhD	+82-870-3931	ossbkang@gmail.com
Contact: JoungYoup Shin, MD	+82-10-5310-7133	sjy820828@gmail.com

Locations

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Korea, Republic of
Seoul National University Boramae Medical Center
Seoul, Korea, Republic of, 07061
Contact: Seung-Baik Kang, MD, PhD +82-2-870-3931 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

Sponsors and Collaborators

Seoul National University Hospital

Investigators

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Principal Investigator:	Seung-Baik Kang, MD, PhD	SMG-SNU Boramae Medical Center

More Information

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.

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. Review.

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.

Onuţu AH. Duloxetine, an antidepressant with analgesic properties - a preliminary analysis. Rom J Anaesth Intensive Care. 2015 Oct;22(2):123-128. Review.

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.

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.

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Responsible Party:	Seung-Baik Kang, Professor, Seoul National University Hospital
ClinicalTrials.gov Identifier:	NCT03792828
Other Study ID Numbers:	SNUBMC_20181128
First Posted:	January 3, 2019 Key Record Dates
Last Update Posted:	January 3, 2019
Last Verified:	January 2019

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Studies a U.S. FDA-regulated Drug Product:	No
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by Seung-Baik Kang, Seoul National University Hospital:


total knee replacement arthroplasty total knee arthroplasty central censitization	duloxetine serotonin-norepinephrine reuptake inhibitors pre-emptive effect

Additional relevant MeSH terms:

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Osteoarthritis Osteoarthritis, Knee Arthritis Joint Diseases Musculoskeletal Diseases Rheumatic Diseases Duloxetine Hydrochloride Serotonin and Noradrenaline Reuptake Inhibitors Neurotransmitter Uptake Inhibitors Membrane Transport Modulators	Molecular Mechanisms of Pharmacological Action Neurotransmitter Agents Physiological Effects of Drugs Analgesics Sensory System Agents Peripheral Nervous System Agents Antidepressive Agents Psychotropic Drugs Dopamine Agents

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