Dexamethasone Twice for Pain Treatment of Total Knee Arthroplasty

NCT ID: NCT03506789

Last Updated: 2020-10-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

485 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-09-14

Study Completion Date

2020-06-07

Brief Summary

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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

Detailed Description

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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); B) 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

* One-year follow-up with EQ-5D-5L (EuroQuols - 5 dimension - 5 level score), Oxford-Knee-Score and mortality including need for medical attention.
* Troponin (TnI) levels 24 and 48 hours postoperatively (only at Naestved Hospital).
* Analysis of high and low pain responders.
* 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:

* 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')
* opioid related adverse events (AE)

* level of nausea, sedation and dizziness at 24 and 48 h
* number of vomiting episodes 0-24 and 24-48 h"
* use of anti-emetics 0-24 and 24-48 h

Conditions

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Postoperative Pain

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Treatment A:

24 mg dexamethasone i.v. perioperatively and 24 mg dexamethasone i.v. on the first postoperative day

Group Type ACTIVE_COMPARATOR

Dexamethasone

Intervention Type DRUG

Dexamethasone 24 mg

Treatment B:

24 mg dexamethasone i.v. perioperatively and placebo (isotonic saline) i.v. on the first postoperative day

Group Type ACTIVE_COMPARATOR

Dexamethasone

Intervention Type DRUG

Dexamethasone 24 mg

Placebos

Intervention Type DRUG

Isotonic saline

Placebo

Placebo (isotonic saline) i.v. perioperatively and placebo (isotonic saline) i.v. on the first postoperative day

Group Type PLACEBO_COMPARATOR

Placebos

Intervention Type DRUG

Isotonic saline

Interventions

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Dexamethasone

Dexamethasone 24 mg

Intervention Type DRUG

Placebos

Isotonic saline

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Scheduled for unilateral, primary total knee arthroplasty
* ASA 1-3
* BMI ≥ 18.0 and ≤ 40.0
* Negative urine HCG pregnancy test and use of anti-conception for women in the fertile age
* 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

* Patients who cannot cooperate with the trial
* Concomitant participation in another trial involving medication
* Patients who cannot understand or speak Danish
* Patients with allergy to medication used in the trial
* 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.
* Patients with at daily use of systemic glucocorticoids
* 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.
* Dysregulated diabetes (investigators judgement)
* Patients suffering from alcohol and/or drug abuse - based on the investigator's judgement
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Naestved Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ole Mathiesen, MD, PhD, Assoc Prof

Role: STUDY_CHAIR

Department of Anaesthesiology, Zealand University Hospital, Køge

Daniel Hägi-Pedersen, MD, PhD

Role: STUDY_CHAIR

Department of Anaesthesiology, Næstved Hospital

Jørgen B Dahl, DMSc

Role: STUDY_CHAIR

Department of Anaesthesiology, Bispebjerg Hospital

Kasper S Gasbjerg, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Anaesthesiology, Næstved Hospital

Troels H Lunn, DMSc

Role: STUDY_CHAIR

Department of Anaesthesiology, Bispebjerg Hospital

Locations

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Gildhøj Privathospital

Brøndby, , Denmark

Site Status

Bispebjerg Hospital

Copenhagen, , Denmark

Site Status

Sjællands Universitetshospital, Køge

Køge, , Denmark

Site Status

Næstsved Sygehus

Næstved, , Denmark

Site Status

Odense Universitetshospital

Odense, , Denmark

Site Status

Countries

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Denmark

References

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Molgaard AK, Gasbjerg KS, Mathiesen O, Hagi-Pedersen D, Gogenur I. Dexamethasone vs. placebo modulation of the perioperative blood immune proteome in patients undergoing total knee arthroplasty. BMC Anesthesiol. 2025 Mar 21;25(1):136. doi: 10.1186/s12871-025-03003-3.

Reference Type DERIVED
PMID: 40119286 (View on PubMed)

Derby CB, Gasbjerg KS, Hagi-Pedersen D, Lunn TH, Pedersen NA, Lindholm P, Brorson S, Schroder HM, Thybo KH, Bagger J, Lindberg-Larsen M, Overgaard S, Jakobsen JC, Mathiesen O. Prolonged effects of dexamethasone following total knee arthroplasty: A pre-planned sub-study of the DEX-2-TKA trial. Acta Anaesthesiol Scand. 2024 Jan;68(1):35-42. doi: 10.1111/aas.14319. Epub 2023 Sep 14.

Reference Type DERIVED
PMID: 37709280 (View on PubMed)

Gasbjerg KS, Hagi-Pedersen D, Lunn TH, Laursen CC, Holmqvist M, Vinstrup LO, Ammitzboell M, Jakobsen K, Jensen MS, Pallesen MJ, Bagger J, Lindholm P, Pedersen NA, Schroder HM, Lindberg-Larsen M, Norskov AK, Thybo KH, Brorson S, Overgaard S, Jakobsen JC, Mathiesen O. Effect of dexamethasone as an analgesic adjuvant to multimodal pain treatment after total knee arthroplasty: randomised clinical trial. BMJ. 2022 Jan 4;376:e067325. doi: 10.1136/bmj-2021-067325.

Reference Type DERIVED
PMID: 34983775 (View on PubMed)

Gasbjerg KS, Hagi-Pedersen D, Lunn TH, Overgaard S, Pedersen NA, Bagger J, Lindholm P, Brorson S, Schroder HM, Thybo KH, Mathiesen O, Jakobsen JC. DEX-2-TKA - DEXamethasone twice for pain treatment after Total Knee Arthroplasty: Detailed statistical analysis plan for a randomized, blinded, three-group multicentre clinical trial. Acta Anaesthesiol Scand. 2020 Jul;64(6):839-846. doi: 10.1111/aas.13560. Epub 2020 Mar 3.

Reference Type DERIVED
PMID: 32048274 (View on PubMed)

Gasbjerg KS, Hagi-Pedersen D, Lunn TH, Jakobsen JC, Overgaard S, Pedersen NA, Bagger J, Lindholm P, Brorson S, Schroder HM, Thybo KH, Mathiesen O. DEX-2-TKA-DEXamethasone twice for pain treatment after Total Knee Arthroplasty: A protocol for a randomized, blinded, three-group multicentre clinical trial. Acta Anaesthesiol Scand. 2020 Feb;64(2):267-275. doi: 10.1111/aas.13481. Epub 2019 Oct 18.

Reference Type DERIVED
PMID: 31544230 (View on PubMed)

Other Identifiers

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SM1-KAKG-2018

Identifier Type: -

Identifier Source: org_study_id

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