TY - JOUR

T1 - DEX-2-TKA - DEXamethasone twice for pain treatment after Total Knee Arthroplasty

T2 - Detailed statistical analysis plan for a randomized, blinded, three-group multicentre clinical trial

AU - Gasbjerg, Kasper S.

AU - Hägi-Pedersen, Daniel

AU - Lunn, Troels H.

AU - Overgaard, Søren

AU - Pedersen, Niels Anker

AU - Bagger, Jens

AU - Lindholm, Peter

AU - Brorson, Stig

AU - Schrøder, Henrik M.

AU - Thybo, Kasper H.

AU - Mathiesen, Ole

AU - Jakobsen, Janus C.

PY - 2020/7

Y1 - 2020/7

N2 - 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).

AB - 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).

KW - detailed statistical analysis plan

KW - DEX-2-TKA

KW - dexamethasone

KW - multimodal analgesia

KW - pain

KW - post-operative pain

KW - total knee arthroplasty

U2 - 10.1111/aas.13560

DO - 10.1111/aas.13560

M3 - Journal article

C2 - 32048274

AN - SCOPUS:85081019398

VL - 64

SP - 839

EP - 846

JO - Acta Anaesthesiologica Scandinavica

JF - Acta Anaesthesiologica Scandinavica

SN - 0001-5172

IS - 6

ER -