Dexamethasone and Pain Following Total Knee Arthroplasty
Condition: Acute Pain; Chronic Pain
MeSH terms: Chronic Pain; Acute Pain
Intervention: Dexamethasone; Placebo
Intervention description: Intravenous dexamethasone at incision and 24h after incision will be compared in 3 doses and placebo administered in a fourth group; Placebo injection of saline at surgical incision and a repeat placebo saline injection 24h after incision.
Intervention MeSH terms: Dexamethasone; Dexamethasone acetate; BB 1101
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 45.0
Sex: All
Minimum age: 55 Years
Healthy volunteers: No
Keywords: Knee arthroplasty; Dexamethasone; Acute pain; Chronic pain

Summary:

      The purpose of the study is three fold. First to determine the ideal dose of dexamethasone
      intraoperatively that will reduce acute pain and opioid consumption. Second determine if
      dexamethasone at the time of surgery reduces chronic pain following total knee arthroplasty
      and finally determine if a pro-inflammatory environment makes patients susceptible to chronic
      pain after surgery and can dexamethasone alter this environment. Patients undergoing total
      knee arthroplasty will be randomized to four groups ( 0mg, 6mg, 12mg and 24mg dexamethasone)
      and assessments will be made of acute and chronic pain and quality of life measures. Blood
      samples will be drawn to assess Interleukin levels and for Macrophage sorting. For the
      primary efficacy endpoint of reduction of opioid consumption over 24 hours after surgery the
      dexamethasone regimen group will be compared to standard of care group using t-test. For
      comparisons of the secondary efficacy endpoints, t-test, Chi-square test and Fisher's Exact
      test will be used. Risks of this study include the risks of venipuncture and intravenous
      dexamethasone administration.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients scheduled to undergo unilateral total knee arthroplasty.

          -  American Society of Anesthesiology (ASA) Physical Class 1-3.

          -  BMI <40 kg/m2

        Exclusion Criteria:

          -  Revision surgery.

          -  Bilateral total knee arthroplasty.

          -  Unicompartmental knee arthroplasty.

          -  Patients with a contraindication to regional anesthesia. This includes abnormal
             clotting, skin infection in groin or near the back, the presence of neurological
             disorders or anatomical abnormalities of the vertebral column.

          -  Contraindications or known drug interactions with dexamethasone.

          -  Use of any of the following medications within the times specified before surgery:

               -  Long-acting opioid medication within 3 days.

               -  Any opioid medication within 24 hours.

          -  Body weight less than 50 kilograms (~110 pounds).

          -  Planned administration of another investigational product or procedure during the
             subject's participation in this study.

          -  Suspected, or known addiction to or abuse of illicit drug(s), prescription
             medicine(s), or alcohol within the past 2 years.

          -  Uncontrolled anxiety, schizophrenia, or other psychiatric disorder that, in the
             opinion of the Investigator, may interfere with study assessments or compliance.

          -  Current or historical evidence of any clinically significant disease or condition
             that, in the opinion of the Investigator, may increase the risk of surgery or
             complicate the subject's postoperative course.

          -  Significant medical conditions or laboratory results that, in the opinion of the
             Investigator, indicate an increased vulnerability to study drugs and procedures, and
             expose the subject to an unreasonable risk as a result of participating in this
             clinical trial, such as: debilitating diseases, acute illnesses, hypotension, partial
             or complete conduction block, impaired cardiac function (Ejection fraction under 35%),
             epilepsy, myasthenia gravis), severe renal impairment (creatinine > 1.8), comorbid
             conditions associated with an immunocompromised status, such as blood dyscrasias,
             HIV/AIDS, or recent chemotherapy.