Influence of Patient Sex on Pain Control and Multimodal Analgesia in Total Knee Arthroplasty
Condition: Knee Osteoarthritis; Pain, Postoperative
MeSH terms: Pain, Postoperative
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): Multimodal analgesia including pregabalin; Multimodal analgesia not including pregabalin
Intervention type(s): Other; Other
Intervention description(s): 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.; Standardized protocol for our institution with multiple medications used for pain (NSAIDs, opioids, dexamethasone) and non-narcotic spinal.
Intervention MeSH terms: Pregabalin
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention 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 (Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment