Knee OsteoarthritisPhase 4NCT03792828
Pre-emptive Effect of Duloxetine in the Second Knee in Staged Total Knee Arthroplasty
A Phase 4 study testing Duloxetine HCl 30mg in people with Knee Osteoarthritis, run by Seoul National University Hospital at 1 site in South Korea.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Knee Osteoarthritis
- What is being tested?
- Duloxetine HCl 30mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteSouth Korea
- Study dates
- Jan 2019to Dec 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Candidate for staged bilateral total knee replacement arthroplasty due to osteoarthritis of the knee.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
South Korea1 site
Seoul National University Boramae Medical Center
Seoul, 07061
Seung-Baik Kang, MD, PhD, +82-2-870-3931, ossbkang@gmail.com
Seung-Baik Kang, MD, PhD
About this study
Official title: 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.
Read the 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.
- Conditions
- Knee Osteoarthritis
- Being tested
- Duloxetine HCl 30mg
- Keywords
- total knee replacement arthroplasty, total knee arthroplasty, central censitization, duloxetine, serotonin-norepinephrine reuptake inhibitors, pre-emptive effect
- Medical subject headings
- Osteoarthritis, Knee
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Duloxetine HCl 30mgDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Control | Active comparator | Duloxetine HCl 30mg is not used. Receives: Drug: Duloxetine HCl 30mg |
| Duloxetine | Experimental | 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. Receives: Drug: Duloxetine HCl 30mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pain VAS
Pain VAS(11-point numeric scale: 0-11) at rest, maximal knee flexion and maximal knee extension
Measured: day 7 (inpatient)
Secondary outcomes (3)
Central censitization
DN4 (Douleur Neuropathique 4)
Measured: Preop. day 1, 2, 7 (inpatient) , Postop. 6 week, 3 month
Opioid consumption
Opioid conversion to Morphine IV
Measured: 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
Measured: Preop. day 1, 2 (inpatient) , Postop. 6 week, 3 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jan 2019
- Study startJan 2019 (estimated)
- Primary completionOct 2019 (estimated)
- Study completionDec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Knee OsteoarthritisStudies of the same condition, open and under way.
- More trials run by Seoul National University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Seoul National University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Seung-Baik Kang, Seoul National University Hospital
- Investigators
- Seung-Baik Kang, MD, PhD, Principal investigator, SMG-SNU Boramae Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03792828
- Sponsor's protocol ID
- SNUBMC_20181128
- Status last verified
- Jan 2019
- First submitted
- 28 Nov 2018
- Last updated
- 3 Jan 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
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.
PubMed 28077538Scott 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.
PubMed 24891574Hussain 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.
PubMed 24426845Sun 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.
PubMed 26068371Kumar 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.
PubMed 27089957Onutu AH. Duloxetine, an antidepressant with analgesic properties - a preliminary analysis. Rom J Anaesth Intensive Care. 2015 Oct;22(2):123-128.
PubMed 28913467Forster 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.
PubMed 16877597Kim 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.
PubMed 23994101YaDeau 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.
PubMed 27387351
Study at a glance
From the registry record, last updated by the sponsor on 3 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pre-emptive Effect of Duloxetine in the Second Knee in Staged Total Knee Arthroplasty: A Randomized Controlled Study
- ClinicalTrials.gov ID
- NCT03792828
- Acronym / sponsor ID
- SNUBMC_20181128
- Conditions
- Knee Osteoarthritis
- Keywords
- total knee replacement arthroplasty, total knee arthroplasty, central censitization, duloxetine, serotonin-norepinephrine reuptake inhibitors, pre-emptive effect
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Seoul National University HospitalUniversity, hospital or other
- Study start
- Jan 2019 (estimated)
- Primary completion
- Oct 2019 (estimated)
- Study completion
- Dec 2019 (estimated)
- First posted
- 3 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control | Active comparator | Drug: Duloxetine HCl 30mgDuloxetine HCl 30mg is not used. |
| Duloxetine | Experimental | Drug: Duloxetine HCl 30mgOne 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. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Candidate for staged bilateral total knee replacement arthroplasty due to osteoarthritis of the knee.
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Duloxetine HCl 30mgIn 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. | Drug | Control, Duloxetine |
Primary outcome
Pain VAS
Time frame: day 7 (inpatient)
Pain VAS(11-point numeric scale: 0-11) at rest, maximal knee flexion and maximal knee extension
3 secondary outcomes
Central censitization
Time frame: Preop. day 1, 2, 7 (inpatient) , Postop. 6 week, 3 month
Opioid consumption
Time frame: Preop. day 1, 2, 7 (inpatient) , Postop. 6 week, 3 month
Pain VAS
Time frame: Preop. day 1, 2 (inpatient) , Postop. 6 week, 3 month
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jan 2019.
- Background: PubMed 28077538Shin 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.
- Background: PubMed 24891574Scott 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.
- Background: PubMed 24426845Hussain 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.
- Background: PubMed 26068371Sun 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.
- Background: PubMed 27089957Kumar 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.
- Background: PubMed 28913467Onutu AH. Duloxetine, an antidepressant with analgesic properties - a preliminary analysis. Rom J Anaesth Intensive Care. 2015 Oct;22(2):123-128.
- Background: PubMed 16877597Forster 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.
- Background: PubMed 23994101Kim 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.
- Background: PubMed 27387351YaDeau 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Seung-Baik Kang, MD, PhD principal investigator
SMG-SNU Boramae Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Duloxetine HCl 30mg in people with Knee Osteoarthritis, run by Seoul National University Hospital at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Seung-Baik Kang, MD, PhD (+82-870-3931, ossbkang@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pain VAS (time frame: day 7 (inpatient)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03792828, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jan 2019.