Influence of Patient Sex on Pain Control and Multimodal Analgesia in Total Knee Arthroplasty

NCT ID: NCT04471233

Last Updated: 2024-10-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 250 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-09
• Study Completion Date: 2023-06-20

Brief 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. 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:

1. Multimodal analgesia regimen including pregabalin;

2. 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Multimodal analgesia regimen including pregabalin

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

Group Type: EXPERIMENTAL

Multimodal analgesia including pregabalin

Intervention Type: OTHER

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 regimen not including pregabalin

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

Group Type: ACTIVE_COMPARATOR

Multimodal analgesia not including pregabalin

Intervention Type: OTHER

Standardized protocol for our institution with multiple medications used for pain (NSAIDs, opioids, dexamethasone) and non-narcotic spinal.

Interventions

Multimodal analgesia including pregabalin

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.

Intervention Type: OTHER

Multimodal analgesia not including pregabalin

Standardized protocol for our institution with multiple medications used for pain (NSAIDs, opioids, dexamethasone) and non-narcotic spinal.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Provision of signed and dated informed consent form

2. Stated willingness to comply with all study procedures and availability for the duration of the study

3. Male or female, age 18-80

4. Undergoing primary unilateral TKA for primary osteoarthritis

5. English speaking

6. Patients whose primary residence is in a home and not a facility or rehabilitation center.

Exclusion Criteria

1. Chronic (>6 months) use of neuromodulators pregabalin or gabapentin.

2. Pregnancy or lactation

3. Prior history of adverse reactions to pregabalin

4. Coexisting chronic pain condition rated ≥50mm on 100-mm VAS requiring narcotics.

5. Coexisting condition leading to sedation or dizziness

6. Kidney disease

7. History of angioedema

8. History of depression with suicidal ideation.

9. Extensive history of opioid/ substance use and/or abuse.

10. Receiving active or maintenance treatment for cancer or solid organ and/or marrow transplant.

11. Patient staying less than one night in the hospital.

12. Patients with a history of chronic obstructive pulmonary disease (COPD) with supplementary oxygen requirements.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Northwell Health

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jonathan Danoff, MD

Role: PRINCIPAL_INVESTIGATOR

Northwell Health

Locations

Northwell Health Orthopedic Institute at Great Neck

Great Neck, New York, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 23794645 (View on PubMed)

Berkley KJ. Sex differences in pain. Behav Brain Sci. 1997 Sep;20(3):371-80; discussion 435-513. doi: 10.1017/s0140525x97221485.

Reference Type: BACKGROUND

PMID: 10097000 (View on PubMed)

Anderson GD. Gender differences in pharmacological response. Int Rev Neurobiol. 2008;83:1-10. doi: 10.1016/S0074-7742(08)00001-9.

Reference Type: RESULT

PMID: 18929073 (View on PubMed)

Sodhi 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.

Reference Type: DERIVED

PMID: 39307204 (View on PubMed)

Other Identifiers

20-0139

Identifier Type: -

Identifier Source: org_study_id