TY - JOUR
T1 - Conservative vs liberal fluid therapy in septic shock (CLASSIC) trial-Protocol and statistical analysis plan
AU - Meyhoff, Tine Sylvest
AU - Hjortrup, Peter Buhl
AU - Moller, Morten Hylander
AU - Wetterslev, Jorn
AU - Lange, Theis
AU - Kjaer, Maj-Brit Norregaard
AU - Jonsson, Andreas Bender
AU - Hjortso, Carl Johan Steensen
AU - Cronhjort, Maria
AU - Laake, Jon Henrik
AU - Jakob, Stephan M.
AU - Nalos, Marek
AU - Pettila, Ville
AU - van der Horst, Iwan
AU - Ostermann, Marlies
AU - Mouncey, Paul
AU - Rowan, Kathy
AU - Cecconi, Maurizio
AU - Ferrer, Ricard
AU - Malbrain, Manu L. N. G.
AU - Ahlstedt, Christian
AU - Hoffmann, Soren
AU - Bestle, Morten Heiberg
AU - Nebrich, Lars
AU - Russell, Lene
AU - Vang, Marianne
AU - Rasmussen, Michael Lindhardt
AU - Solling, Christoffer
AU - Rasmussen, Bodil Steen
AU - Brochner, Anne Craveiro
AU - Perner, Anders
PY - 2019/10
Y1 - 2019/10
N2 - Introduction Intravenous (IV) fluid is a key intervention in the management of septic shock. The benefits and harms of lower versus higher fluid volumes are unknown and thus clinical equipoise exists. We describe the protocol and detailed statistical analysis plan for the conservative versus liberal approach to fluid therapy of septic shock in the Intensive Care (CLASSIC) trial. The aim of the CLASSIC trial is to assess benefits and harms of IV fluid restriction versus standard care in adult intensive care unit (ICU) patients with septic shock. Methods CLASSIC trial is an investigator-initiated, international, randomised, stratified, and analyst-blinded trial. We will allocate 1554 adult patients with septic shock, who are planned to be or are admitted to an ICU, to IV fluid restriction versus standard care. The primary outcome is mortality at day 90. Secondary outcomes are serious adverse events (SAEs), serious adverse reactions (SARs), days alive at day 90 without life support, days alive and out of the hospital at day 90 and mortality, health-related quality of life (HRQoL), and cognitive function at 1 year. We will conduct the statistical analyses according to a pre-defined statistical analysis plan, including three interim analyses. For the primary analysis, we will use logistic regression adjusted for the stratification variables comparing the two interventions in the intention-to-treat (ITT) population. Discussion The CLASSIC trial results will provide important evidence to guide clinicians' choice regarding the IV fluid therapy in adults with septic shock.
AB - Introduction Intravenous (IV) fluid is a key intervention in the management of septic shock. The benefits and harms of lower versus higher fluid volumes are unknown and thus clinical equipoise exists. We describe the protocol and detailed statistical analysis plan for the conservative versus liberal approach to fluid therapy of septic shock in the Intensive Care (CLASSIC) trial. The aim of the CLASSIC trial is to assess benefits and harms of IV fluid restriction versus standard care in adult intensive care unit (ICU) patients with septic shock. Methods CLASSIC trial is an investigator-initiated, international, randomised, stratified, and analyst-blinded trial. We will allocate 1554 adult patients with septic shock, who are planned to be or are admitted to an ICU, to IV fluid restriction versus standard care. The primary outcome is mortality at day 90. Secondary outcomes are serious adverse events (SAEs), serious adverse reactions (SARs), days alive at day 90 without life support, days alive and out of the hospital at day 90 and mortality, health-related quality of life (HRQoL), and cognitive function at 1 year. We will conduct the statistical analyses according to a pre-defined statistical analysis plan, including three interim analyses. For the primary analysis, we will use logistic regression adjusted for the stratification variables comparing the two interventions in the intention-to-treat (ITT) population. Discussion The CLASSIC trial results will provide important evidence to guide clinicians' choice regarding the IV fluid therapy in adults with septic shock.
KW - INTENSIVE-CARE
KW - SEPSIS-PROTOCOL
KW - MISSING DATA
KW - RESUSCITATION
KW - MANAGEMENT
KW - MORTALITY
KW - VOLUMES
KW - ADULTS
U2 - 10.1111/aas.13434
DO - 10.1111/aas.13434
M3 - Article
SN - 0001-5172
VL - 63
SP - 1262
EP - 1271
JO - Acta Anaesthesiologica Scandinavica
JF - Acta Anaesthesiologica Scandinavica
IS - 9
ER -