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.
DEX-2-TKA
detailed statistical analysis plan
dexamethasone
multimodal analgesia
pain
post-operative pain
total knee arthroplasty
Journal
Acta anaesthesiologica Scandinavica
ISSN: 1399-6576
Titre abrégé: Acta Anaesthesiol Scand
Pays: England
ID NLM: 0370270
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
31
01
2020
accepted:
03
02
2020
pubmed:
13
2
2020
medline:
11
8
2021
entrez:
13
2
2020
Statut:
ppublish
Résumé
Optimization of post-operative pain treatment is of upmost importance. Multimodal analgesia is the main post-operative pain treatment principle, but the evidence on optimal analgesic combinations is unclear. With the "DEXamethasone twice for pain treatment after TKA" trial, we aim to investigate the role of one or two doses of glucocorticoid for post-operative pain treatment after total knee arthroplasty. To ensure transparency and minimization of bias, we present this article with a detailed statistical analysis plan, to be published before the last participant is enrolled. "DEXamethasone twice for pain treatment after TKA" (DEX-2-TKA) is a randomized, blinded, three-group multicentre clinical trial. Participants will be randomized to one of three intervention groups: single dose of iv dexamethasone 24 mg, two consecutive doses of iv dexamethasone 24 mg or matching iv placebo. All three intervention groups will receive paracetamol, NSAID (ibuprofen) and local infiltration analgesia. Participants, treatment providers, outcome assessors, data managers, statisticians and conclusion drawers will be blinded to the allocated intervention. The primary outcome is total opioid consumption (iv morphine milligram equivalents) 0-48 hours post-operatively. Secondary outcomes are (1) visual analogue scale pain levels: (a) during active 45 degrees flexion of the knee at 24 and 48 hours post-operatively, (b) at rest at 24 and 48 hours post-operatively, and (c) during 0-24 hours (highest score) and 24-48 hours post-operatively (highest score); and (2) the proportion of participants with one or more adverse events within 48 hours post-operatively. The DEX-2-TKA trial will provide high quality data regarding benefits and harms of adding one or two high-doses of dexamethasone to a multimodal analgesic regimen. EudraCT: 2018-001099-39 (08/06-18); ClinicalTrials.gov: NCT03506789 (24/04-2019).
Sections du résumé
BACKGROUND
Optimization of post-operative pain treatment is of upmost importance. Multimodal analgesia is the main post-operative pain treatment principle, but the evidence on optimal analgesic combinations is unclear. With the "DEXamethasone twice for pain treatment after TKA" trial, we aim to investigate the role of one or two doses of glucocorticoid for post-operative pain treatment after total knee arthroplasty. To ensure transparency and minimization of bias, we present this article with a detailed statistical analysis plan, to be published before the last participant is enrolled.
METHODS
"DEXamethasone twice for pain treatment after TKA" (DEX-2-TKA) is a randomized, blinded, three-group multicentre clinical trial. Participants will be randomized to one of three intervention groups: single dose of iv dexamethasone 24 mg, two consecutive doses of iv dexamethasone 24 mg or matching iv placebo. All three intervention groups will receive paracetamol, NSAID (ibuprofen) and local infiltration analgesia. Participants, treatment providers, outcome assessors, data managers, statisticians and conclusion drawers will be blinded to the allocated intervention. The primary outcome is total opioid consumption (iv morphine milligram equivalents) 0-48 hours post-operatively. Secondary outcomes are (1) visual analogue scale pain levels: (a) during active 45 degrees flexion of the knee at 24 and 48 hours post-operatively, (b) at rest at 24 and 48 hours post-operatively, and (c) during 0-24 hours (highest score) and 24-48 hours post-operatively (highest score); and (2) the proportion of participants with one or more adverse events within 48 hours post-operatively.
DISCUSSION
The DEX-2-TKA trial will provide high quality data regarding benefits and harms of adding one or two high-doses of dexamethasone to a multimodal analgesic regimen.
TRIAL REGISTRATION
EudraCT: 2018-001099-39 (08/06-18); ClinicalTrials.gov: NCT03506789 (24/04-2019).
Substances chimiques
Glucocorticoids
0
Dexamethasone
7S5I7G3JQL
Banques de données
ClinicalTrials.gov
['NCT03506789']
Types de publication
Journal Article
Multicenter Study
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
839-846Informations de copyright
© 2020 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.
Références
Chou R, Gordon DB, de Leon-Casasola OA, et al. Management of Postoperative Pain: A Clinical Practice Guideline From the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists’ Committee on Regional Anesthesia, Executive Committee, and Administrative Council. J Pain. 2016;17:131-157.
Karlsen APH, Wetterslev M, Hansen SE, Hansen MS, Mathiesen O, Dahl JB. Postoperative pain treatment after total knee arthroplasty: a systematic review. PLoS ONE. 2017;12:1-53.
Dahl JB, Nielsen RV, Wetterslev J, et al. Post-operative analgesic effects of paracetamol, NSAIDs, glucocorticoids, gabapentinoids and their combinations: a topical review. Acta Anaesthesiol Scand. 2014;58:1165-1181.
Mathiesen O, Wetterslev J, Kontinen VK, et al. Adverse effects of perioperative paracetamol, NSAIDs, glucocorticoids, gabapentinoids and their combinations: a topical review. Acta Anaesthesiol Scand. 2014;58:1182-1198.
Fabritius ML, Geisler A, Petersen PL, et al. Gabapentin for post-operative pain management - a systematic review with meta-analyses and trial sequential analyses. Acta Anaesthesiol Scand. 2016;60:1188-1208.
Fabritius ML, Strøm C, Koyuncu S, et al. Benefit and harm of pregabalin in acute pain treatment : a systematic review with meta-analyses and trial sequential analyses. Br J Anaesth. 2017;119:775-791.
Gan TJ, Diemunsch P, Habib AS, et al. Consensus guidelines for the management of postoperative nausea and vomiting. Anesth Analg. 2014;118:85-113.
Whitlock RP, Devereaux PJ, Teoh KH, et al. Methylprednisolone in patients undergoing cardiopulmonary bypass (SIRS): a randomised, double-blind, placebo-controlled trial. Lancet. 2015;386:1243-1253.
Backes JR, Bentley JC, Politi JR, Chambers BT. Dexamethasone reduces length of hospitalization and improves postoperative pain and nausea after total joint arthroplasty: a prospective, randomized controlled trial. J Arthroplasty. 2013;28:11-17.
Lunn TH, Kristensen BB, Andersen L, et al. Effect of high-dose preoperative methylprednisolone on pain and recovery after total knee arthroplasty: a randomized, placebo-controlled trial. Br J Anaesth. 2011;106:230-238.
Li X, Sun Z, Han C, He L, Wang B. A systematic review and meta-analysis of intravenous glucocorticoids for acute pain following total hip arthroplasty. Medicine (Baltimore). 2017;96. https://doi.org/10.1097/MD.0000000000006872.
Shen S, Gao Z, Liu J. The efficacy and safety of methylprednisolone for pain control after total knee arthroplasty: a meta-analysis of randomized controlled trials. Int J Surg. 2018;57:91-100. https://doi.org/10.1016/j.ijsu.2018.07.009.
Zhou G, Ma L, Jing J, Jiang H. A meta-analysis of dexamethasone for pain management in patients with total knee arthroplasty. Medicine (Baltimore). 2018;97. https://doi.org/10.1097/MD.0000000000011753.
International conference on harmonisation guideline for international conference on harmonisation of technical requirements for registration of pharmaceuticals for human use. ICH harmonised tripartite guideline. Guideline for good clinical practice E6 (R1 [Internet]). 1996. https://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6/E6_R1_Guideline.pdf. Accessed July 3, 2019.
Gasbjerg KS, Pedersen DH, Lunn TH, et al. 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;64:267-275.
Association AM. Guidelines for the content of statistical analysis plans in clinical trials. J Am Med Assoc. 2017;318:2337-2343.
ICH Harmonised Tripartite Guideline: Statistical Principles for Clinical Trials E9 [Internet]. International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use. 1998. https://database.ich.org/sites/default/files/E9_Guideline.pdf
Thybo KH, Hägi-Pedersen D, Dahl JB, et al. Effect of combination of paracetamol (acetaminophen) and ibuprofen vs either alone on patient-controlled morphine consumption in the first 24 hours after total hip arthroplasty - The PANSAID randomized clinical trial. J Am Med Assoc. 2019;321:562-571.
Ong CKS, Seymour RA, Lirk P, Merry AF. Combining paracetamol (acetaminophen) with nonsteroidal antiinflammatory drugs: a qualitative systematic review of analgesic efficacy for acute postoperative pain. Anesth Analg. 2010;110:1170-1179.
Motulsky HJ. Sample size for nonparametric tests [Internet]. GraphPad Stat. Guid. https://www.graphpad.com/guides/prism/8/statistics/stat_sample_size_for_nonparametric_.htm. Accessed July 3, 2019.
Herdman M, Gudex C, Lloyd A, et al. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res. 2011;20:1727-1736.
Murray DW, Fitzpatrick R, Rogers K, et al. The use of the Oxford hip and knee scores. J Bone Jt Surg. 2007;89:1010-1014.
Jakobsen JC, Ovesen C, Winkel P, Hilden J, Gluud C, Wetterslev J. Power estimations for non-primary outcomes in randomised clinical trials. BMJ Open. 2019;9:e027092.
Jakobsen JC, Gluud C, Winkel P, Lange T, Wetterslev J. The thresholds for statistical and clinical significance - a five-step procedure for evaluation of intervention effects in randomised clinical trials. BMC Med Res Methodol. 2014;14:1-12.
Jakobsen JC, Gluud C, Wetterslev J, Winkel P. When and how should multiple imputation be used for handling missing data in randomised clinical trials - a practical guide with flowcharts. BMC Med Res Methodol. 2017;17(1):1-10.
Qu Y, Zhao YD, Rahardja D. Wilcoxon-Mann-Whitney test: Stratify or not? J Biopharm Stat. 2008;18:1103-1111.
Gotzsche PC. Blinding during data analysis and writing of manuscripts. Control Clin Trials. 1996;17:285-293.
Nielsen EE, Nørskov AK, Lange T, et al. Assessing assumptions for statistical analyses in randomised clinical trials. BMJ Evidence-Based Med. 2019;24:185-189.
Juul S, Frydenberg M. An Introduction to Stata for Health Researchers, 4th edn. College Station, TX: Stata Press; 2014.
Oliveira AG. Biostatistics Decoded. Hoboken, NJ: Wiley; 2013.