DEX-2-TKA: Dexamethasone Twice for Pain Treatment of Total Knee Arthroplasty
Study Details
Study Description
Brief Summary
Dexamethasone twice for pain treatment after total knee arthroplasty - A Placebo-controlled, randomised, parallel 3-group multicentre trial of one and two doses of dexamethasone for postoperative treatment
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Detailed Description
Trial name: Dexamethasone twice for pain treatment of total knee arthroplasty - A randomized blinded placebo-controlled clinical trial
Trial Acronym: DEX-2-TKA
Background: Effective postoperative pain management is essential for the well-being and rehabilitation of the surgical patient. No "gold standard" exists for pain treatment after total knee arthroplasty (TKA) since combinations of different analgesic treatments are used with nearly no evidence for combined analgesic efficacy. A single perioperative dose of glucocorticoid (GCC) (i.e. dexamethasone) has well established effects on postoperative nausea and vomiting, and may be beneficial for postoperative pain. A recent trial suggested that an additional postoperative dose of GCC improved postoperative pain treatment. Recent systematic reviews, sub-studies of RCTs and cohort studies of perioperative GCC raised no concern regarding serious adverse events of a single dose GCC for non-cardiac surgery. However, optimal dose, combination and regimen of perioperative GCC remains unsettled.
Objective: To establish the analgesic effect and safety of one and two consecutive days of a single dose of dexamethasone after TKA. GCC will be administered in combination with paracetamol, NSAID (ibuprofen), and local infiltration analgesia.
Intervention: The participants will be randomised in three groups: A) 24 mg dexamethasone i.v. perioperative (POD0) and 24 mg dexamethasone i.v. on the first postoperative day (POD1);
- 24 mg dexamethasone i.v. POD0 and placebo (isotonic saline) i.v. on POD1; and C) placebo i.v. on POD0 and POD1.
Design and trial size: Placebo-controlled, randomised, parallel 3-group multicentre trial with adequate centralised computer-generated allocation sequence and allocation concealment with unknown block size. Assessor, investigator, caregivers and participants will all be blinded. A total of 423 eligible participants are needed to detect a difference of 10 mg morphine for the first 48 hours postoperatively with a standard deviation of 23 mg, an overall familywise type 1 error rate of 0.05 and a type 2 error rate of 0.10. To compensate for uncertainty of the distribution a surplus of 15 % is added, thus a total of 486 patients will be included. To maintain an overall familywise error rate of 0.05 the sample size estimation is based on pairwise comparisons of the primary outcome between the three groups (three comparisons) with an individual type I error rate of 0.0167.
Sub studies: The investigators plan the following substudies
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One-year follow-up with EQ-5D-5L (EuroQuols - 5 dimension - 5 level score), Oxford-Knee-Score and mortality including need for medical attention.
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Troponin (TnI) levels 24 and 48 hours postoperatively (only at Naestved Hospital).
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Analysis of high and low pain responders.
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Establishment of a bio-bank (blood-samples) for future studies (only at Naestved Hospital).
Due to decisions made by the Steering Committee at our meeting the 14th of May 2019 in Køge, Region Zealand, Denmark, the secondary outcomes have been rearranged and divided into secondary outcomes and other (eksplorative) outcomes. Furthermore an additional explorative endpoint is added: Number of patients with a permanent use of opioids 90 days after surgery.
No data was unblinded or analyzed to aid the decisions.
After the last patient was included, but prior to data analysis and unmasking, the Steering Committee decided to include the following explorative outcomes in the main article reporting results from this trial. The decision was made by consensus via email 4th of October 2020:
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proportion of participants with one or more severe adverse event (SAE), including death, within 90 days after surgery (SAE defined according to ICH-GCP-guidelines, except 'prolongation of hospitalisation')
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opioid related adverse events (AE)
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level of nausea, sedation and dizziness at 24 and 48 h
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number of vomiting episodes 0-24 and 24-48 h"
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use of anti-emetics 0-24 and 24-48 h
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Treatment A: 24 mg dexamethasone i.v. perioperatively and 24 mg dexamethasone i.v. on the first postoperative day |
Drug: Dexamethasone
Dexamethasone 24 mg
|
| Active Comparator: Treatment B: 24 mg dexamethasone i.v. perioperatively and placebo (isotonic saline) i.v. on the first postoperative day |
Drug: Dexamethasone
Dexamethasone 24 mg
Drug: Placebos
Isotonic saline
|
| Placebo Comparator: Placebo Placebo (isotonic saline) i.v. perioperatively and placebo (isotonic saline) i.v. on the first postoperative day |
Drug: Placebos
Isotonic saline
|
Outcome Measures
Primary Outcome Measures
- Cumulative usage of morphine 0-48 hours postoperatively [0-48 hours postoperatively]
Morphine administered both as patient-controlled analgesia (PCA) i.v. morphine 0-24 hours and oral morphine on demand 24-48 hours, and any other supplemental morphine administered postoperatively. Consumption in mg
Secondary Outcome Measures
- VAS-pain scores (visual analogue scale (VAS)) [24 and 48 hours postoperatively]
with active 45 degrees flexion of the knee (VAS) at 24 and 48 hours postoperatively at rest at 24 and 48 hours postoperatively highest score during 0-24 hours and 24-48 hours
- Adverse events, patient-reported [0-48 hours postoperatively]
Number of patients with one or more patient-reported adverse event in the intervention period
Other Outcome Measures
- Number of patients with one or more serious adverse events (SAE) [90 days postoperatively]
Number of patients with one or more serious adverse events (SAE), including death, within 90 days after surgery defined as SAE (according to ICH-GCP-guidelines), except "prolongation of hospitalisation"
- 90 days follow-up [90 days postoperatively]
Number of patients with need for medical attention and/or intervention including need for anti-biotics and/or re-operation
- Total need of i.v. morphine 0-24 hours postoperatively [0-24 hours postoperatively]
Consumption in mg
- Total need of oral morphine 24-48 hours postoperatively [24-48 hours postoperatively]
Consumption in mg
- VAS-pain scores (visual analogue scale (VAS)) [6, 24 and 48 hours postoperatively hours postoperatively]
with active 45 degrees flexion of the knee (VAS) at 6 hours postoperatively at rest at 6 postoperatively average score during 0-24 hours and 24-48 hours
- Timed up and go (TUG) test at 24 and 48 hours including maximum pain during the TUG test. [24 and 48 hours postoperatively]
The timed up and go test is performed at 24 and 48 hours postoperatively. The participant will be placed on a chair, 3 meters from a line. After the command "Go" the participant will Stand up from the chair Walk to the line on the floor Turn Walk back to the chair Sit down again. The time will be measured from "Go" to the participant is sitting again.
- Adverse events, nausea [0-48 hours postoperatively]
Level of nausea at 6, 24 and 48 hours postoperatively Scale: none, mild, moderate, severe
- Adverse events, sedation [0-48 hours postoperatively]
Level of sedation at 6, 24 and 48 hours postoperatively Scale: none, mild, moderate, severe
- Adverse events, dizziness [0-48 hours postoperatively]
Level of dizziness at 6, 24 and 48 hours postoperatively Scale: none, mild, moderate, severe
- Adverse events, vomiting [0-48 hours postoperatively]
Number of vomiting episodes (0-48 hours) measured in the periods 0-24 and 24-48 hours postoperatively
- Consumption of antiemetics in the period 0-24 and 24-48 hours postoperatively [0-48 hours postoperatively]
Use of ondansetron and DHB (Dehydrobenzperidol)
- Quality of sleep 0-24 and 24-48 hours postoperatively [0-48 hours postoperatively]
Scale: very bad, fairly bad, fairly good, very good
- Level of fatigue at 24 and 48 hours postoperatively [24 and 48 hours postoperatively]
Scale: none, mild, moderate, severe
- NRS-pain scores 3-7 days postoperatively [3-7 days postoperatively]
Two daily NRS-scores: One in the morning and one in the evening
- Quality of sleep 3-7 days postoperatively [3-7 days postoperatively]
Scale: very bad, fairly bad, fairly good, very good
- Satisfaction with postoperative pain treatment after 7 days [7 days postoperatively]
Scale: very bad, fairly bad, fairly good, very good
- Proportion of participants with permanent use of opioids 90 days after surgery [90 days postoperatively]
Number of patients with prescripción for painkillers
- 90 days follow-up using EQ5D5L [90 days postoperatively]
Qualitative participant reported assessments using EQ5D5L (Questionaire - with one NRS (0-100))
- 90 days follow-up using Oxford-Knee-Score [90 days postoperatively]
Qualitative participant reported assessments using Oxford-Knee-Score (Questionaire, scale 12-60 points)
Eligibility Criteria
Criteria
Inclusion Criteria:
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Scheduled for unilateral, primary total knee arthroplasty
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ASA 1-3
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BMI ≥ 18.0 and ≤ 40.0
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Negative urine HCG pregnancy test and use of anti-conception for women in the fertile age
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Patients who gave their written informed consent to participating in the trial after having fully understood the contents of the protocol and restrictions
Exclusion Criteria:
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Patients who cannot cooperate with the trial
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Concomitant participation in another trial involving medication
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Patients who cannot understand or speak Danish
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Patients with allergy to medication used in the trial
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Patients with daily use of high dose opioid (> oral morphine 30 mg/day or oxycodone 30 mg/day or tramadol 150 mg/day) or any use of other opioids including methadone and transdermal opioids.
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Patients with at daily use of systemic glucocorticoids
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Contraindications against ibuprofen or paracetamol, for example previous ulcer, known heart failure, known liver failure, or known renal failure (eGRF < 60 ml/kg/1,73m2), known thrombocytopenia (<100 bil/l); or against treatment with glucocorticoids.
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Dysregulated diabetes (investigators judgement)
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Patients suffering from alcohol and/or drug abuse - based on the investigator's judgement
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Gildhøj Privathospital | Brøndbyvester | Denmark | 2605 | |
| 2 | Bispebjerg Hospital | Copenhagen | Denmark | 2400 | |
| 3 | Sjællands Universitetshospital, Køge | Køge | Denmark | 4600 | |
| 4 | Næstsved Sygehus | Næstved | Denmark | 4700 | |
| 5 | Odense Universitetshospital | Odense | Denmark | 5000 |
Sponsors and Collaborators
- Naestved Hospital
Investigators
- Study Chair: Ole Mathiesen, MD, PhD, Assoc Prof, Department of Anaesthesiology, Zealand University Hospital, Køge
- Study Chair: Daniel Hägi-Pedersen, MD, PhD, Department of Anaesthesiology, Næstved Hospital
- Study Chair: Jørgen B Dahl, DMSc, Department of Anaesthesiology, Bispebjerg Hospital
- Principal Investigator: Kasper S Gasbjerg, MD, Department of Anaesthesiology, Næstved Hospital
- Study Chair: Troels H Lunn, DMSc, Department of Anaesthesiology, Bispebjerg Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SM1-KAKG-2018