Acute PainPhase 4NCT02271698
Dexamethasone and Pain Following Total Knee Arthroplasty
A Phase 4 study testing Dexamethasone in people with Acute Pain and Chronic Pain, run by Duke University at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 55 years and older
- Conditions the study is for
- Acute Pain, Chronic Pain
- What is being tested?
- Dexamethasone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2014to Jul 2016
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients scheduled to undergo unilateral total knee arthroplasty.
- American Society of Anesthesiology (ASA) Physical Class 1-3.
- BMI <40 kg/m2
Who cannot join
- 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:
Show all 14Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Acute Pain, Chronic Pain
- Being tested
- Dexamethasone, Placebo
- Keywords
- Knee arthroplasty, Dexamethasone, Acute pain, Chronic pain
- Medical subject headings
- Acute Pain, Chronic Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexamethasoneDrug
Also called Dexamethasone acetate
Intravenous dexamethasone at incision and 24h after incision will be compared in 3 doses and placebo administered in a fourth group
PlaceboOther
Placebo injection of saline at surgical incision and a repeat placebo saline injection 24h after incision.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6, 12, 18, 24, 36 hours after surgery
Change in Opioid Consumption
mg of morphine equivalents
Measured: 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
The Western Ontario and McMaster Universities Osteoarthritis Index measures 17 items for functional limitation (score range 0-68). Higher score = higher difficulty with the task.
Measured: 30 days, 3 and 6 months following surgery
Change in Chronic Pain as Measured by Brief Pain Inventory Questionnaire
Brief pain inventory questionnaire will be administered generating a score (0-40). Higher scores reflect higher perceived pain.
Measured: Baseline at enrollment, 3 months and 6 months after surgery
Change in Functional Status as Measured by Brief Pain Inventory Questionnaire
Brief pain inventory questionnaire will be administered generating a score (0-70). Higher scores reflect higher perceived pain interference.
Measured: Baseline at Enrollment, 3 and 6 months after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2014 (estimated)
- Study startDec 2014
- Primary completionJan 2016
- Study completionJul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acute PainStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Stuart A Grant, MB ChB, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02271698
- Sponsor's protocol ID
- Pro00055895
- Status last verified
- Jan 2018
- First submitted
- 16 Oct 2014
- Last updated
- 20 Feb 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Perioperative Dexamethasone to Promote Systemic Pro-Resolution Phenotype for Prevention of Acute and Chronic Pain Post-Total Knee Arthroplasty.
- ClinicalTrials.gov ID
- NCT02271698
- Acronym / sponsor ID
- Pro00055895
- Conditions
- Acute Pain, Chronic Pain
- Keywords
- Knee arthroplasty, Dexamethasone, Acute pain, Chronic pain
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Study start
- Dec 2014 (actual)
- Primary completion
- Jan 2016 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 22 Oct 2014 (estimated)
- Results
- Posted 3 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Dexamethasone 6mg | Active comparator | Drug: DexamethasonePatients 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. |
| Dexamethasone 12mg | Active comparator | Drug: DexamethasonePatients 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. |
| Dexamethasone 24mg | Active comparator | Drug: DexamethasonePatients 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. |
| Placebo | Placebo comparator | Other: PlaceboPatients 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. |
Who may qualify
- Ages
- 55 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patients scheduled to undergo unilateral total knee arthroplasty.
- American Society of Anesthesiology (ASA) Physical Class 1-3.
- BMI <40 kg/m2
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DexamethasoneAlso: Dexamethasone acetateIntravenous dexamethasone at incision and 24h after incision will be compared in 3 doses and placebo administered in a fourth group | Drug | Dexamethasone 12mg, Dexamethasone 24mg, Dexamethasone 6mg |
| PlaceboPlacebo injection of saline at surgical incision and a repeat placebo saline injection 24h after incision. | Other | Placebo |
Primary outcome
Change in Visual Analogue Pain Score
Time frame: 6, 12, 18, 24, 36 hours after surgery
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.
Change in Opioid Consumption
Time frame: 6, 12, 18, 24, 36 hours after surgery
mg of morphine equivalents
3 secondary outcomes
Change in Functional Status as Measured by Western Ontario and McMaster Universities Osteoarthritis Index
Time frame: 30 days, 3 and 6 months following surgery
Change in Chronic Pain as Measured by Brief Pain Inventory Questionnaire
Time frame: Baseline at enrollment, 3 months and 6 months after surgery
Change in Functional Status as Measured by Brief Pain Inventory Questionnaire
Time frame: Baseline at Enrollment, 3 and 6 months after surgery
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Acute Pain
Not yet recruiting
Human Experimental Models of Pain (HEMP)
Acute Pain
RecruitingPhase 2
REctus Sheath Trial
Acute Pain, Postoperative Pain, Acute
Not yet recruitingPhase 2
A Clinical Trial of MK-6916 in Participants With Pain After Bunion Removal Surgery (MK-6916-007)
Pain Management
Not yet recruitingPhase 2
Investigating the Analgesic Potential of (2R,6R)-HNK in Acute Pain in Healthy Volunteers
Healthy Volunteers
Not yet recruiting
Post-operative Pain and Clinical Outcome After Single-cone Obturation With a Calcium Silicate-based Versus Epoxy Resin Sealer
Post Operative Pain, Acute, Irreversible Pulpitis (Toothache)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stuart A Grant, MB ChB principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Dexamethasone in people with Acute Pain and Chronic Pain, run by Duke University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Visual Analogue Pain Score (time frame: 6, 12, 18, 24, 36 hours after surgery). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Feb 2018.