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

Primary Purpose

Knee Osteoarthritis

Status
Unknown status
Phase
Phase 4
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Duloxetine HCl 30mg
Sponsored by
Seoul National University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Knee Osteoarthritis focused on measuring total knee replacement arthroplasty, total knee arthroplasty, central censitization, duloxetine, serotonin-norepinephrine reuptake inhibitors, pre-emptive effect

Eligibility Criteria

18 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Seoul National University Boramae Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Control

Duloxetine

Arm Description

Duloxetine HCl 30mg is not used.

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.

Outcomes

Primary Outcome Measures

Pain VAS
Pain VAS(11-point numeric scale: 0-11) at rest, maximal knee flexion and maximal knee extension

Secondary Outcome Measures

Central censitization
DN4 (Douleur Neuropathique 4)
Opioid consumption
Opioid conversion to Morphine IV
Pain VAS
Pain VAS(11-point numeric scale: 0-11) at rest, maximal knee flexion and maximal knee extension

Full Information

First Posted
November 28, 2018
Last Updated
January 1, 2019
Sponsor
Seoul National University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03792828
Brief Title
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

2. Study Status

Record Verification Date
January 2019
Overall Recruitment Status
Unknown status
Study Start Date
January 2019 (Anticipated)
Primary Completion Date
October 2019 (Anticipated)
Study Completion Date
December 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Seoul National University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Knee Osteoarthritis
Keywords
total knee replacement arthroplasty, total knee arthroplasty, central censitization, duloxetine, serotonin-norepinephrine reuptake inhibitors, pre-emptive effect

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
90 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Control
Arm Type
Active Comparator
Arm Description
Duloxetine HCl 30mg is not used.
Arm Title
Duloxetine
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Duloxetine HCl 30mg
Intervention Description
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.
Primary Outcome Measure Information:
Title
Pain VAS
Description
Pain VAS(11-point numeric scale: 0-11) at rest, maximal knee flexion and maximal knee extension
Time Frame
day 7 (inpatient)
Secondary Outcome Measure Information:
Title
Central censitization
Description
DN4 (Douleur Neuropathique 4)
Time Frame
Preop. day 1, 2, 7 (inpatient) , Postop. 6 week, 3 month
Title
Opioid consumption
Description
Opioid conversion to Morphine IV
Time Frame
Preop. day 1, 2, 7 (inpatient) , Postop. 6 week, 3 month
Title
Pain VAS
Description
Pain VAS(11-point numeric scale: 0-11) at rest, maximal knee flexion and maximal knee extension
Time Frame
Preop. day 1, 2 (inpatient) , Postop. 6 week, 3 month

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Seung-Baik Kang, MD, PhD
Phone
+82-870-3931
Email
ossbkang@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
JoungYoup Shin, MD
Phone
+82-10-5310-7133
Email
sjy820828@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Seung-Baik Kang, MD, PhD
Organizational Affiliation
SMG-SNU Boramae Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Seoul National University Boramae Medical Center
City
Seoul
ZIP/Postal Code
07061
Country
Korea, Republic of
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Seung-Baik Kang, MD, PhD
Phone
+82-2-870-3931
Email
ossbkang@gmail.com
First Name & Middle Initial & Last Name & Degree
Seung-Baik Kang, MD, PhD
First Name & Middle Initial & Last Name & Degree
Chong Bum Chang, MD, PhD
First Name & Middle Initial & Last Name & Degree
Moon Jong Chang, MD, PhD
First Name & Middle Initial & Last Name & Degree
Joung Youp Shin, MD
First Name & Middle Initial & Last Name & Degree
Whang Kim, MD
First Name & Middle Initial & Last Name & Degree
Dong Whan Suh, MD
First Name & Middle Initial & Last Name & Degree
Jong Byung Oh, MD

12. IPD Sharing Statement

Citations:
PubMed Identifier
28077538
Citation
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.
Results Reference
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PubMed Identifier
24891574
Citation
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.
Results Reference
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PubMed Identifier
24426845
Citation
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.
Results Reference
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PubMed Identifier
26068371
Citation
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.
Results Reference
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PubMed Identifier
27089957
Citation
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.
Results Reference
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PubMed Identifier
28913467
Citation
Onutu AH. Duloxetine, an antidepressant with analgesic properties - a preliminary analysis. Rom J Anaesth Intensive Care. 2015 Oct;22(2):123-128.
Results Reference
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PubMed Identifier
16877597
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.
Results Reference
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PubMed Identifier
23994101
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.
Results Reference
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PubMed Identifier
27387351
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.
Results Reference
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Pre-emptive Effect of Duloxetine in the Second Knee in Staged Total Knee Arthroplasty

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