Clinical trial NCT02271698: Dexamethasone and Pain Following Total Knee Arthroplasty
Official title: Perioperative Dexamethasone to Promote Systemic Pro-Resolution Phenotype for Prevention of Acute and Chronic Pain Post-Total Knee Arthroplasty.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Acute Pain
Chronic Pain
Keywords: Knee arthroplasty
Dexamethasone
Acute pain
Chronic pain
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2014-10-22
Enrollment: 45
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: This is a Phase IV single center, prospective, randomized, double-blind, dose response study designed to evaluate the optimum dose of dexamethasone to administer as an analgesic in total knee arthroplasty surgery. Randomization will be performed using computer software and the randomization order will be written and enclosed in envelopes in the study office. A total of 40 patients will be randomized to receive different doses of dexamethasone intravenously at induction of anesthesia with the same dose repeated 24 hours later. The dose groups are: 0mg, 6mg, 12mg, 24mg. The groups will be evenly divided into 10 subjects in each group. Patients will be cared for using established standard of care anesthetic and multi modal analgesia pathway used clinically at Duke University Medical Center. Knee arthroplasty generally occurs in patients over 65 years of age and an inclusion criteria is age 55 years or older is included in the study. Regional anesthesia is more technically challenging in morbidly obese patients. Because of an increased failure rate of regional anesthesia in morbidly obese patients an upper limit BMI of 40 is included in the study design.

Anesthetic regime. The anesthesia will be standard of care apart from the administration of the study drug.

Study Drug. After randomization the first dose of intravenous dexamethasone will be administered by the anesthesia care team immediately before surgery. The subject and study personnel will be blinded to the dose. The patient will be sedated and the study personnel will not be in the operating room. The dose will be recorded on the anesthesia record.

The second dose of dexamethasone will be prescribed by the PI. This will be prescribed electronically to be administered to the subject on the floor 24 hours after the first dose.

Surgery The surgery will proceed normally with no difference for the study.

Postoperative Pain Management Patients in all groups will receive standard of care postoperative analgesic regimen.

Blood Samples Blood will be drawn in preop holding (Time 0) for Interleukin 6, Interleukin10 and for macrophage sorting.

Blood samples will be repeated for Interleukin 6 and Interleukin10 at 10-14, 22-26 and 33-39hours after surgery.

Blood samples for macrophage sorting will be repeated at 33-39hours. The total blood collected will be 30ml on the day of surgery and 10 ml post operative day 1 for an overall total of 40cc.

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.

Primary outcomes:
measure: Change in Visual Analogue Pain Score
timeFrame: 6, 12, 18, 24, 36 hours after surgery
measure: Change in Opioid Consumption
timeFrame: 6, 12, 18, 24, 36 hours after surgery
Secondary outcomes:
measure: Change in Functional Status as Measured by Western Ontario and McMaster Universities Osteoarthritis Index
timeFrame: 30 days, 3 and 6 months following surgery
measure: Change in Chronic Pain as Measured by Brief Pain Inventory Questionnaire
timeFrame: Baseline at enrollment, 3 months and 6 months after surgery
measure: Change in Functional Status as Measured by Brief Pain Inventory Questionnaire
timeFrame: Baseline at Enrollment, 3 and 6 months after surgery
Other outcomes:
measure: Change in Macrophage Proliferation
timeFrame: Samples will be taken immediately pre incision and will be repeated at 33-39hours
measure: Change in Interleukin 6 and 10 Levels
timeFrame: Sample immediately prior to incision and at 10-14, 22-26 and 33-39hours after surgery.
Locations:
city: Durham
country: United States
facility: DUMC
state: North Carolina
Study officials:
affiliation: Duke University
name: Stuart A Grant, MB ChB
role: PRINCIPAL_INVESTIGATOR
References: