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

NCT04471233 | Completed DMC

• 1 other identifier: 20-0139
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 1

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.

Conditions

Knee Osteoarthritis; Pain, Postoperative

Outcome Measures

Primary Outcomes (1)

• 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.

  48 hours

Secondary Outcomes (7)

• Assess how sex differences and multimodal analgesia regimens influence physical function

  26 weeks

• Assess how sex differences and multimodal analgesia regimens influence postoperative narcotic medication use

  72 hours

• Assess how sex differences and multimodal analgesia regimens influence postoperative narcotic medication cessation

  2 weeks

• Assess how sex differences and multimodal analgesia regimens influence chronic postoperative pain

  26 weeks

• Assess how sex differences and multimodal analgesia regimens influence mental health

  week 26

Study Arms (2)

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

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

Other: Multimodal analgesia not including pregabalin

Interventions

Multimodal analgesia including pregabalin 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 including pregabalin

Multimodal analgesia not including pregabalin OTHER

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

Multimodal analgesia regimen not including pregabalin

Eligibility Criteria

• Age: 18 Years - 80 Years
• Gender Eligibility Details: Eligibility will be based on biological sex
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Northwell Health: lead

Study Sites (1)

Northwell Health Orthopedic Institute at Great Neck

Great Neck, New York, 11021, United States

Location

Related Publications (4)

• 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.

  PMID: 23794645 BACKGROUND

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

  PMID: 10097000 BACKGROUND

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

  PMID: 18929073 RESULT

• 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.

  PMID: 39307204 DERIVED

MeSH Terms

Conditions

Osteoarthritis, Knee; Pain, Postoperative

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Study Officials

• Jonathan Danoff, MD

  Northwell Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Care providers, and investigators will all be blinded to patient group identity.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Intervention is preoperative and 14 days postoperatively. Patients will be assigned to either multimodal analgesia regimen. No crossing over of patients will occur.

Study Record Dates

• First Submitted: May 21, 2020
• First Posted: July 15, 2020
• Study Start: December 9, 2020
• Primary Completion: June 20, 2023
• Study Completion: June 20, 2023
• Last Updated: October 1, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)