Conservative vs liberal fluid therapy in septic shock (CLASSIC) trial—Protocol and statistical analysis plan
Year: 2019
Type: article
Study design: Study Protocol
Abstract: 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.
DOI: 10.1111/aas.13434
Authors: Tine Sylvest Meyhoff, Peter Buhl Hjortrup, Morten Hylander Møller, Jørn Wetterslev, Theis Lange, Maj‐Brit Nørregaard Kjær, Andreas Bender Jonsson, Carl Johan Steensen Hjortsø, Maria Cronhjort, Jon Henrik Laake, Stephan M. Jakob, Marek Nalos, Ville Pettilä, Iwan van der Horst, Marlies Ostermann, Paul Mouncey, Kathy Rowan, Maurizio Cecconi, Ricard Ferrer, Manu L. N. G. Malbrain, Christian Ahlstedt, Søren Hoffmann, Morten Heiberg Bestle, Lars Nebrich, Lene Russell, Marianne Vang, Michael Lindhardt Rasmussen, Christoffer Sølling, Bodil Steen Rasmussen, Anne Craveiro Brøchner, Anders Perner
Institutions: Copenhagen University Hospital, Rigshospitalet, Centre for Research in Intensive Care, University of Copenhagen, Karolinska Institutet, Stockholm South General Hospital, Oslo University Hospital, University of Bern, University Hospital of Bern, University Hospital Plzen, University of Helsinki, Helsinki University Hospital, University Medical Center Groningen, Guy's Hospital, St Thomas' Hospital, Guy's and St Thomas' NHS Foundation Trust, Intensive Care National Audit & Research Centre, IRCCS Humanitas Research Hospital, Vall d'Hebron Hospital Universitari, Vrije Universiteit Brussel, Universitair Ziekenhuis Brussel, Karolinska University Hospital, Bispebjerg Hospital, Nordsjællands Hospital, Zealand University Hospital Køge, Roskilde Sygehus, Zealand University Hospital, Copenhagen Academy for Medical Education and Simulation, Regional Hospital Randers, Regionshospitalet Herning, Regionshospitalet Viborg, Aalborg University Hospital, Kolding Hospital, Lillebaelt Hospital
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: Novo Nordisk, Novo Nordisk Fonden
Award: G874901763
OpenAlex ID: W2954089999