Knee OsteoarthritisNCT04471233
Influence of Patient Sex on Pain Control and Multimodal Analgesia in Total Knee Arthroplasty
A study testing Multimodal analgesia including pregabalin and Multimodal analgesia not including pregabalin in people with Knee Osteoarthritis and Pain, Postoperative, run by Northwell Health at 1 site in United States.
Trial summary
The purpose of this study is to examine the influence of sex on postoperative pain, following total knee arthroplasty (TKA). Patients will first be stratified by sex and then be randomized into one of two multimodal analgesic regimen (MAR), which differ in presence of pregabalin. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Knee Osteoarthritis, Pain, Postoperative
- What is being tested?
- Multimodal analgesia including pregabalin and Multimodal analgesia not including pregabalin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 250 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Dec 2020to 20 Jun 2023
- Phase
- Interventional
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of signed and dated informed consent form
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Male or female, age 18-80
- Undergoing primary unilateral TKA for primary osteoarthritis
- English speaking
- Patients whose primary residence is in a home and not a facility or rehabilitation center.
Who cannot join
- Chronic (>6 months) use of neuromodulators pregabalin or gabapentin.
- Pregnancy or lactation
- Prior history of adverse reactions to pregabalin
- Coexisting chronic pain condition rated ≥50mm on 100-mm VAS requiring narcotics.
- Coexisting condition leading to sedation or dizziness
- Kidney disease
Show all 12Show fewer
- History of angioedema
- History of depression with suicidal ideation.
- Extensive history of opioid/ substance use and/or abuse.
- Receiving active or maintenance treatment for cancer or solid organ and/or marrow transplant.
- Patient staying less than one night in the hospital.
- Patients with a history of chronic obstructive pulmonary disease (COPD) with supplementary oxygen requirements.
Trial locations and contacts
1 site in 1 country.
United States1 site
Northwell Health Orthopedic Institute at Great Neck
Great Neck, New York, 11021
About this study
The purpose of this study is to examine the influence of sex on postoperative pain, following total knee arthroplasty (TKA). Patients will first be stratified by sex and then be randomized into one of two multimodal analgesic regimen (MAR), which differ in presence of pregabalin. We hypothesize that that acute postoperative pain scores are different over time between males and females and between multimodal analgesic regimens following TKA. Investigators will be blinded to which multimodal group patients are in. Patients will complete surveys in the office, during their hospital stay, and at followup intervals for up to six months.
Read the detailed description
The overall goal of this study is to better understand the influence of patient-sex on postoperative pain perception in men versus women following total knee arthroplasty (TKA) utilizing two different multimodal analgesia regimens.
Pregabalin is a neuromuscular antagonist of voltage gated calcium channels at the post-synaptic dorsal horns in the spinal cord and brain. It binds to the alpha-2-delta subunit and interrupts pain signal transmission. The use of pregabalin as part of multimodal pain control has been associated with a decrease in postoperative opioid use.
This will be a randomized, single-blinded control trial in which patients either will or will not receive pregabalin as part of their multimodal analgesia regimen following TKA. It will be performed at a single institution, with multiple tertiary academic centers.
Patients will first be grouped according to their sex, then randomized into one of two arms:
- Multimodal analgesia regimen including pregabalin;
- Multimodal analgesia regimen not including pregabalin.
For the intervention group, patient will be provided with an oral preoperative pregabalin dose of 150mg on the day of surgery. Patient will continue pregabalin 75mg two times a day, for two weeks postoperatively. For both both groups, the operative technique and additional perioperative analgesic modalities will follow a standard protocol.
Primary Endpoint: Acute postoperative pain difference (up to 72 hours), measured by 100mm visual analogue scale (VAS) while at rest and mobilization, between males and females and between multimodal analgesic regimens in patients undergoing TKA.
Secondary Endpoints:
- Pain control measured by 100mm visual analogue scale (VAS) while at rest and mobilization.
- Pain control additionally measured by morphine equivalent units (MEq).
- Number of postoperative days to opioid cessation.
- Pain measured by Knee Injury and Osteoarthritis Outcome Score (KOOS).
- Physical function measured by KOOS, physical component summary (PCS-12) of VR-12.
- Mental health measured by mental component summary (MCS-12) of VR-12.
- Safety will be tracked by adverse reactions reported or observed by investigators. These will be collected via patient communication and review of the medical record.
- Additionally, severity of common short-term postoperative complications like nausea, vomiting, dizziness, and sedation will be assessed by 100mm VAS.
The study recruitment phase is estimated to last for 6 months. Subject followup is 6 months.
- Conditions
- Knee Osteoarthritis, Pain, Postoperative
- Being tested
- Multimodal analgesia including pregabalin, Multimodal analgesia not including pregabalin
- Medical subject headings
- Osteoarthritis, Knee, Pain, Postoperative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Multimodal analgesia including pregabalinOther
Standardized protocol for our institution with multiple medications used for pain (NSAIDs, opioids, dexamethasone) and non-narcotic spinal. Patient will be provided with an preoperative pregabalin dose and will continue medication two weeks postoperatively.
Multimodal analgesia not including pregabalinOther
Standardized protocol for our institution with multiple medications used for pain (NSAIDs, opioids, dexamethasone) and non-narcotic spinal.
| Study group | Role | What they receive |
|---|---|---|
| Multimodal analgesia regimen including pregabalin | Experimental | For the pregabalin group, patient will be provided with an oral preoperative pregabalin dose of 150mg on the day of surgery. Patient will continue pregabalin 75mg two times a day, for two weeks postoperatively. For both the intervention and control groups, the operative technique and additional perioperative analgesic modalities will follow a standard protocol Receives: Other: Multimodal analgesia including pregabalin |
| Multimodal analgesia regimen not including pregabalin | Active comparator | For the non-pregabalin group, patient will be undergo total knee arthroplasty with the same operative technique and additional perioperative analgesic modalities will follow a standard protocol Receives: Other: Multimodal analgesia not including pregabalin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assess influence of sex and multimodal analgesia regimens on acute postoperative pain scores at 48 hours postoperatively, in patients undergoing TKA.
Pain control measured by 100mm visual analogue scale (VAS) while at rest 48 hours after the procedure.
Measured: 48 hours
Secondary outcomes (7)
Assess how sex differences and multimodal analgesia regimens influence physical function
-Pain measured by Knee Injury and Osteoarthritis Outcome Score (KOOS) of week 4, week 12, week 26 postoperatively, compared to baseline.
Measured: 26 weeks
Assess how sex differences and multimodal analgesia regimens influence postoperative narcotic medication use
Pain control additionally measured by morphine equivalent units (MEq) for 24, 48, and 72 hours after the end of the procedure.
Measured: 72 hours
Assess how sex differences and multimodal analgesia regimens influence postoperative narcotic medication cessation
-Number of postoperative days to opioid cessation.
Measured: 2 weeks
Assess how sex differences and multimodal analgesia regimens influence chronic postoperative pain
-Chronic: Pain control measured by 100mm visual analogue scale (VAS) (0 corresponding to no pain and 100 corresponding to worst possible pain) while at rest and mobilization at week 1, week 2, week 4-6, week 12, week 26 postoperatively.
Measured: 26 weeks
Assess how sex differences and multimodal analgesia regimens influence mental health
-Mental health measured by mental component summary (MCS-12) of VR-12 of week 2, week 4, week 12, week 26 postoperatively, compared to baseline.
Measured: week 26
Assess how sex differences and multimodal analgesia regimens influence physical function
-Physical function measured physical component summary (PCS-12) of Veterans Rand-12 (VR-12) at week 2, week 4, week 12, week 26 postoperatively, compared to baseline.
Measured: 26 weeks
Assess how sex differences and multimodal analgesia regimens influence range of motion (ROM)
Range of Motion (ROM) of week 2, week 4, week 12, week 26 postoperatively, compared to baseline.
Measured: 26 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2020
- Study start9 Dec 2020
- Primary completion20 Jun 2023
- Study completion20 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)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 Northwell HealthThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Intervention is preoperative and 14 days postoperatively. Patients will be assigned to either multimodal analgesia regimen. No crossing over of patients will occur.
- Masking
- Triple blind
- Who is masked
- Care provider, Investigator, Outcomes assessor
- Enrolment
- 250 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwell Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jonathan Danoff, MD, Principal investigator, Northwell Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04471233
- Sponsor's protocol ID
- 20-0139
- Status last verified
- Sep 2024
- First submitted
- 21 May 2020
- Last updated
- 1 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Bartley EJ, Fillingim RB. Sex differences in pain: a brief review of clinical and experimental findings. Br J Anaesth. 2013 Jul;111(1):52-8. doi: 10.1093/bja/aet127.
PubMed 23794645Berkley KJ. Sex differences in pain. Behav Brain Sci. 1997 Sep;20(3):371-80; discussion 435-513. doi: 10.1017/s0140525x97221485.
PubMed 10097000Anderson GD. Gender differences in pharmacological response. Int Rev Neurobiol. 2008;83:1-10. doi: 10.1016/S0074-7742(08)00001-9.
PubMed 18929073Sodhi N, Qilleri A, Aprigliano C, Danoff JR. One Size Does Not Fit All: Women Experience More Pain Than Men After Total Knee Arthroplasty. J Arthroplasty. 2025 Apr;40(4):880-886. doi: 10.1016/j.arth.2024.09.028. Epub 2024 Sep 20.
PubMed 39307204
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Influence of Patient Sex on Pain Control and Multimodal Analgesia in Total Knee Arthroplasty
- ClinicalTrials.gov ID
- NCT04471233
- Acronym / sponsor ID
- 20-0139
- Conditions
- Knee Osteoarthritis, Pain, Postoperative
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 250 participants (actual)
- Lead sponsor
- Northwell HealthUniversity, hospital or other
- Study start
- 9 Dec 2020 (actual)
- Primary completion
- 20 Jun 2023 (actual)
- Study completion
- 20 Jun 2023 (actual)
- First posted
- 15 Jul 2020 (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.
The purpose of this study is to examine the influence of sex on postoperative pain, following total knee arthroplasty (TKA). Patients will first be stratified by sex and then be randomized into one of two multimodal analgesic regimen (MAR), which differ in presence of pregabalin. We hypothesize that that acute postoperative pain scores are different over time between males and females and between multimodal analgesic regimens following TKA. Investigators will be blinded to which multimodal group patients are in. Patients will complete surveys in the office, during their hospital stay, and at followup intervals for up to six months.
Detailed description
The overall goal of this study is to better understand the influence of patient-sex on postoperative pain perception in men versus women following total knee arthroplasty (TKA) utilizing two different multimodal analgesia regimens.
Pregabalin is a neuromuscular antagonist of voltage gated calcium channels at the post-synaptic dorsal horns in the spinal cord and brain. It binds to the alpha-2-delta subunit and interrupts pain signal transmission. The use of pregabalin as part of multimodal pain control has been associated with a decrease in postoperative opioid use.
This will be a randomized, single-blinded control trial in which patients either will or will not receive pregabalin as part of their multimodal analgesia regimen following TKA. It will be performed at a single institution, with multiple tertiary academic centers.
Patients will first be grouped according to their sex, then randomized into one of two arms:
- Multimodal analgesia regimen including pregabalin;
- Multimodal analgesia regimen not including pregabalin.
For the intervention group, patient will be provided with an oral preoperative pregabalin dose of 150mg on the day of surgery. Patient will continue pregabalin 75mg two times a day, for two weeks postoperatively. For both both groups, the operative technique and additional perioperative analgesic modalities will follow a standard protocol.
Primary Endpoint: Acute postoperative pain difference (up to 72 hours), measured by 100mm visual analogue scale (VAS) while at rest and mobilization, between males and females and between multimodal analgesic regimens in patients undergoing TKA.
Secondary Endpoints:
- Pain control measured by 100mm visual analogue scale (VAS) while at rest and mobilization.
- Pain control additionally measured by morphine equivalent units (MEq).
- Number of postoperative days to opioid cessation.
- Pain measured by Knee Injury and Osteoarthritis Outcome Score (KOOS).
- Physical function measured by KOOS, physical component summary (PCS-12) of VR-12.
- Mental health measured by mental component summary (MCS-12) of VR-12.
- Safety will be tracked by adverse reactions reported or observed by investigators. These will be collected via patient communication and review of the medical record.
- Additionally, severity of common short-term postoperative complications like nausea, vomiting, dizziness, and sedation will be assessed by 100mm VAS.
The study recruitment phase is estimated to last for 6 months. Subject followup is 6 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Intervention is preoperative and 14 days postoperatively. Patients will be assigned to either multimodal analgesia regimen. No crossing over of patients will occur.
| Arm | Type | Receives |
|---|---|---|
| Multimodal analgesia regimen including pregabalin | Experimental | Other: Multimodal analgesia including pregabalinFor the pregabalin group, patient will be provided with an oral preoperative pregabalin dose of 150mg on the day of surgery. Patient will continue pregabalin 75mg two times a day, for two weeks postoperatively. For both the intervention and control groups, the operative technique and additional perioperative analgesic modalities will follow a standard protocol |
| Multimodal analgesia regimen not including pregabalin | Active comparator | Other: Multimodal analgesia not including pregabalinFor the non-pregabalin group, patient will be undergo total knee arthroplasty with the same operative technique and additional perioperative analgesic modalities will follow a standard protocol |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Provision of signed and dated informed consent form
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Male or female, age 18-80
- Undergoing primary unilateral TKA for primary osteoarthritis
- English speaking
Key exclusion criteria (12 listed)
- Chronic (>6 months) use of neuromodulators pregabalin or gabapentin.
- Pregnancy or lactation
- Prior history of adverse reactions to pregabalin
- Coexisting chronic pain condition rated ≥50mm on 100-mm VAS requiring narcotics.
- Coexisting condition leading to sedation or dizziness
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 |
|---|---|---|
| Multimodal analgesia including pregabalinStandardized protocol for our institution with multiple medications used for pain (NSAIDs, opioids, dexamethasone) and non-narcotic spinal. Patient will be provided with an preoperative pregabalin dose and will continue medication two weeks postoperatively. | Other | Multimodal analgesia regimen including pregabalin |
| Multimodal analgesia not including pregabalinStandardized protocol for our institution with multiple medications used for pain (NSAIDs, opioids, dexamethasone) and non-narcotic spinal. | Other | Multimodal analgesia regimen not including pregabalin |
Primary outcome
Assess influence of sex and multimodal analgesia regimens on acute postoperative pain scores at 48 hours postoperatively, in patients undergoing TKA.
Time frame: 48 hours
Pain control measured by 100mm visual analogue scale (VAS) while at rest 48 hours after the procedure.
7 secondary outcomes
Assess how sex differences and multimodal analgesia regimens influence physical function
Time frame: 26 weeks
Assess how sex differences and multimodal analgesia regimens influence postoperative narcotic medication use
Time frame: 72 hours
Assess how sex differences and multimodal analgesia regimens influence postoperative narcotic medication cessation
Time frame: 2 weeks
Assess how sex differences and multimodal analgesia regimens influence chronic postoperative pain
Time frame: 26 weeks
Assess how sex differences and multimodal analgesia regimens influence mental health
Time frame: week 26
Assess how sex differences and multimodal analgesia regimens influence physical function
Time frame: 26 weeks
Assess how sex differences and multimodal analgesia regimens influence range of motion (ROM)
Time frame: 26 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2024.
- Background: PubMed 23794645Bartley EJ, Fillingim RB. Sex differences in pain: a brief review of clinical and experimental findings. Br J Anaesth. 2013 Jul;111(1):52-8. doi: 10.1093/bja/aet127.
- Background: PubMed 10097000Berkley KJ. Sex differences in pain. Behav Brain Sci. 1997 Sep;20(3):371-80; discussion 435-513. doi: 10.1017/s0140525x97221485.
- Results publication: PubMed 18929073Anderson GD. Gender differences in pharmacological response. Int Rev Neurobiol. 2008;83:1-10. doi: 10.1016/S0074-7742(08)00001-9.
- Derived from this study: PubMed 39307204Sodhi N, Qilleri A, Aprigliano C, Danoff JR. One Size Does Not Fit All: Women Experience More Pain Than Men After Total Knee Arthroplasty. J Arthroplasty. 2025 Apr;40(4):880-886. doi: 10.1016/j.arth.2024.09.028. Epub 2024 Sep 20.
- Individual participant dataSharing planned: No
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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.
Jonathan Danoff, MD principal investigator
Northwell Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Multimodal analgesia including pregabalin and Multimodal analgesia not including pregabalin in people with Knee Osteoarthritis and Pain, Postoperative, run by Northwell Health at 1 site in United States.
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 6 inclusion and 12 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: finished, as of the sponsor's last update on 1 Oct 2024. 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 United States. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assess influence of sex and multimodal analgesia regimens on acute postoperative pain scores at 48 hours postoperatively, in patients undergoing TKA. (time frame: 48 hours). 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 NCT04471233, which also lists 4 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 1 Oct 2024.