Dexamethasone and Pain Following Total Knee Arthroplasty
| Status: | Completed |
|---|---|
| Conditions: | Chronic Pain, Chronic Pain, Chronic Pain |
| Therapuetic Areas: | Musculoskeletal |
| Healthy: | No |
| Age Range: | 55 - Any |
| Updated: | 2/22/2018 |
| Start Date: | December 2014 |
| End Date: | July 2016 |
Perioperative Dexamethasone to Promote Systemic Pro-Resolution Phenotype for Prevention of Acute and Chronic Pain Post-Total Knee Arthroplasty.
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.
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.
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.
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.
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.
We found this trial at
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