TY - JOUR

T1 - Conservative vs. liberal fluid therapy in septic shock - Protocol for secondary Bayesian analyses of the CLASSIC trial

AU - Sivapalan, Praleene

AU - Meyhoff, Tine S.

AU - Hjortrup, Peter B.

AU - Lange, Theis

AU - Moller, Morten Hylander

AU - Perner, Anders

AU - Granholm, Anders

PY - 2022

Y1 - 2022

N2 - Background Clinical equipoise exists regarding intravenous (IV) fluid volumes in sepsis. The Conservative vs. Liberal Approach to fluid therapy of Septic Shock in Intensive Care (CLASSIC) trial investigates the effect of restricted vs. standard IV fluid therapy in 1554 adult intensive care unit patients with septic shock. Methods This protocol describes secondary Bayesian analyses of the primary outcome (90-day all-cause mortality) and three secondary outcomes at day 90. We will analyse all binary outcomes with adjusted Bayesian logistic regressions and present results as conditional relative risks and risk differences with 95% credibility intervals (CrIs). The secondary count outcome will be analysed using adjusted Bayesian linear regression with results summarised as conditional mean differences and ratios of means with 95% Crls. We will use weakly informative priors for the primary analyses, and sceptical and evidence-based priors in the sensitivity analyses. Exact probabilities will be presented for any benefit/harm, clinically important benefit/harm and no clinically important difference. We will assess whether heterogeneity of treatment effects on mortality is present using Bayesian hierarchical models in subgroups and on the continuous scale using models with interactions according to five baseline variables assessing the overall severity of illness and the degree of circulatory and renal impairment. Discussion The outlined analyses will supplement the primary analysis of the CLASSIC trial by describing probabilities of beneficial and harmful effects and evaluating heterogeneity of treatment effects in a framework that may be easier to interpret for researchers and clinicians.

AB - Background Clinical equipoise exists regarding intravenous (IV) fluid volumes in sepsis. The Conservative vs. Liberal Approach to fluid therapy of Septic Shock in Intensive Care (CLASSIC) trial investigates the effect of restricted vs. standard IV fluid therapy in 1554 adult intensive care unit patients with septic shock. Methods This protocol describes secondary Bayesian analyses of the primary outcome (90-day all-cause mortality) and three secondary outcomes at day 90. We will analyse all binary outcomes with adjusted Bayesian logistic regressions and present results as conditional relative risks and risk differences with 95% credibility intervals (CrIs). The secondary count outcome will be analysed using adjusted Bayesian linear regression with results summarised as conditional mean differences and ratios of means with 95% Crls. We will use weakly informative priors for the primary analyses, and sceptical and evidence-based priors in the sensitivity analyses. Exact probabilities will be presented for any benefit/harm, clinically important benefit/harm and no clinically important difference. We will assess whether heterogeneity of treatment effects on mortality is present using Bayesian hierarchical models in subgroups and on the continuous scale using models with interactions according to five baseline variables assessing the overall severity of illness and the degree of circulatory and renal impairment. Discussion The outlined analyses will supplement the primary analysis of the CLASSIC trial by describing probabilities of beneficial and harmful effects and evaluating heterogeneity of treatment effects in a framework that may be easier to interpret for researchers and clinicians.

KW - INTENSIVE-CARE

KW - SEPSIS

KW - MANAGEMENT

KW - MODELS

U2 - 10.1111/aas.14058

DO - 10.1111/aas.14058

M3 - Review

C2 - 35338648

VL - 66

SP - 767

EP - 771

JO - Acta Anaesthesiologica Scandinavica

JF - Acta Anaesthesiologica Scandinavica

SN - 0001-5172

IS - 6

ER -