Dexamethasone and Pain Following Total Knee Arthroplasty

NCT02271698 | Completed Phase 4 Results

• 1 other identifier: Pro00055895
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Pain; Chronic Pain

Keywords

Knee arthroplasty; Dexamethasone; Acute pain; Chronic pain

Outcome Measures

Primary Outcomes (2)

• Change in Visual Analogue Pain Score

  Pain scores at rest and with activity using a verbal rating scales (VRS) of 0-10, where "0" represents no pain and "10" represents worst pain ever.

  6, 12, 18, 24, 36 hours after surgery

• Change in Opioid Consumption

  mg of morphine equivalents

  6, 12, 18, 24, 36 hours after surgery

Secondary Outcomes (3)

• Change in Functional Status as Measured by Western Ontario and McMaster Universities Osteoarthritis Index

  30 days, 3 and 6 months following surgery

• Change in Chronic Pain as Measured by Brief Pain Inventory Questionnaire

  Baseline at enrollment, 3 months and 6 months after surgery

• Change in Functional Status as Measured by Brief Pain Inventory Questionnaire

  Baseline at Enrollment, 3 and 6 months after surgery

Other Outcomes (2)

• Change in Macrophage Proliferation

  Samples will be taken immediately pre incision and will be repeated at 33-39hours

• Change in Interleukin 6 and 10 Levels

  Sample immediately prior to incision and at 10-14, 22-26 and 33-39hours after surgery.

Study Arms (4)

Dexamethasone 6mg

ACTIVE COMPARATOR

Patients receive 6mg iv dexamethasone at surgical incision and a repeat dose of 6mg of dexamethasone 24h after incision. Pain scores and opioid consumption will be assessed using iv opioid patient controlled analgesia totals.

Drug: Dexamethasone

Dexamethasone 12mg

ACTIVE COMPARATOR

Patients receive 12mg iv dexamethasone at surgical incision and a repeat dose of 12mg of dexamethasone 24h after incision. Pain scores and opioid consumption will be assessed using iv opioid patient controlled analgesia totals.

Drug: Dexamethasone

Dexamethasone 24mg

ACTIVE COMPARATOR

Patients receive 24mg iv dexamethasone at surgical incision and a repeat dose of 24mg of dexamethasone 24h after incision. Pain scores and opioid consumption will be assessed using iv opioid patient controlled analgesia totals.

Drug: Dexamethasone

Placebo

PLACEBO COMPARATOR

Patients receive a placebo injection of saline at surgical incision and a repeat placebo saline injection 24h after incision. Pain scores and opioid consumption will be assessed using iv opioid patient controlled analgesia totals.

Other: Placebo

Interventions

Dexamethasone DRUG

Intravenous dexamethasone at incision and 24h after incision will be compared in 3 doses and placebo administered in a fourth group

Also known as: Dexamethasone acetate

Dexamethasone 12mg; Dexamethasone 24mg; Dexamethasone 6mg

Placebo OTHER

Placebo injection of saline at surgical incision and a repeat placebo saline injection 24h after incision.

Placebo

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients scheduled to undergo unilateral total knee arthroplasty.
• American Society of Anesthesiology (ASA) Physical Class 1-3.
• BMI \<40 kg/m2

You may not qualify if:

• 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.

Sponsors & Collaborators

• Duke University: lead

Study Sites (1)

DUMC

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Acute Pain; Chronic Pain

Interventions

Dexamethasone; dexamethasone acetate

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Dr. Stuart Alan Grant
• Organization: Duke University Health System

stuart.grant@duke.edu

919-681-6437

Study Officials

• Stuart A Grant, MB ChB

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2014
• First Posted: October 22, 2014
• Study Start: December 1, 2014
• Primary Completion: January 1, 2016
• Study Completion: July 1, 2016
• Last Updated: February 20, 2018
• Results First Posted: March 3, 2017

Record last verified: 2018-01

Locations

US (1)