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Cited by 47Sepsis Diagnosis and TreatmentHemodynamic Monitoring and TherapyHyperglycemia and glycemic control in critically ill and hospitalized patients

Conservative vs liberal fluid therapy in septic shock (CLASSIC) trial—Protocol and statistical analysis plan

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Meyhoff, Tine Sylvest, Hjortrup, Peter Buhl, Møller, Morten Hylander, Wetterslev, Jørn, Lange, Theis, Kjær, Maj‐Brit Nørregaard, Jonsson, Andreas Bender, Hjortsø, Carl Johan Steensen +23 more·2019·Acta Anaesthesiologica Scandinavica
DOI 10.1111/aas.13434
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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.

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  • The absence of clear benefit following administration of colloids compared to crystalloid solutions supports the use of crystalloid solutions in resuscitation of patients with sepsis and septic shock.

    “The absence of clear benefit following the administration of colloids compared to crystalloid solutions supports the use of crystalloid solutions in the resuscitation of patients with sepsis and septic shock (324).”

    From Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. (2021) · cites this paper as [324]

    The protocol’s Accepted Article section permits a 250–500 mL IV crystalloid bolus, supporting crystalloid use in its septic-shock resuscitation protocol. It does not compare outcomes with colloids or state that colloids lack a clear benefit, so the claim’s rationale is unsupported. Page numbers were not available in our copy. (LLM, conf=0.82)

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Authors
Meyhoff, T. S., Hjortrup, P. B., Møller, M. H., Wetterslev, J., Lange, T., Kjær, M. N., Jonsson, A. B., Hjortsø, C. J. S., Cronhjort, M., Laake, J. H., Jakob, S. M., Nalos, M., Pettilä, V., van der Horst, I., Ostermann, M., Mouncey, P., Rowan, K., Cecconi, M., Ferrer, R., Malbrain, M. L. N. G., Ahlstedt, C., Hoffmann, S., Bestle, M. H., Nebrich, L., Russell, L., Vang, M., Rasmussen, M. L., Sølling, C., Rasmussen, B. S., Brøchner, A. C., & Perner, A.
Affiliations
  • Copenhagen University Hospital (DK)
  • University of Copenhagen (DK)
  • Karolinska Institutet (SE)
  • Oslo University Hospital (NO)
  • University of Bern (CH)
  • University Hospital Plzen (CZ)
  • University of Helsinki (FI)
  • Department of Intensive Care University Medical Centre Groningen Groningen The Netherlands
  • Guy's Hospital (GB)
  • Intensive Care National Audit & Research Centre (GB)
  • IRCCS Humanitas Research Hospital (IT)
  • Vall d'Hebron Hospital Universitari (ES)
  • Vrije Universiteit Brussel (BE)
  • Karolinska University Hospital (SE)
  • Bispebjerg Hospital (DK)
  • Zealand University Hospital Køge (DK)
  • Roskilde Sygehus (DK)
  • Regional Hospital Randers (DK)
  • Regionshospitalet Herning (DK)
  • Regionshospitalet Viborg (DK)
  • Aalborg University Hospital (DK)
  • Kolding Hospital (DK)
Corresponding author
Meyhoff, Tine Sylvest
ORCID
Venue
Acta Anaesthesiologica Scandinavica
Publisher
Wiley
Published
2019-07-24
Volume
63
Issue
9
Pages
1262-1271
ISSN
  • 0001-5172 (ISSN-L)
  • 1399-6576
DOI
10.1111/aas.13434
OpenAlex
W2954089999
Cited by
47
References
5
Citations by year
2026: 2 · 2025: 4 · 2024: 3 · 2023: 9 · 2022: 16 · 2021: 8 · 2020: 3 · 2019: 2
FWCI
5.52
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Acta Anaesthesiologica Scandinavica (publishedVersion)
  • PubMed (publishedVersion)
  • University of Southern Denmark Research Portal (University of Southern Denmark) (acceptedVersion, other-oa)
  • Bern Open Repository and Information System (University of Bern) (submittedVersion)
  • Työväentutkimus Vuosikirja (submittedVersion, other-oa)
  • VBN Forskningsportal (Aalborg Universitet) (submittedVersion, other-oa)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
  • VUBIR (Vrije Universiteit Brussel) (submittedVersion)
Funders
  • Novo Nordisk
  • Novo Nordisk Fonden (NNF17OC0028608)
Topics
  • Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
  • Health Sciences › Medicine › Surgery › Hemodynamic Monitoring and Therapy
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hyperglycemia and glycemic control in critically ill and hospitalized patients
Keywords
septic shock, intravenous fluid therapy, fluid restriction, conservative fluid management, intensive care unit patients, 90-day mortality, health-related quality of life, cognitive function, serious adverse events
MeSH terms
Adult, Aged, Aged, 80 and over, Clinical Protocols, Cognition, Critical Care, Data Interpretation, Statistical, Double-Blind Method, Female, Fluid Therapy, Humans, Male, Middle Aged, Quality of Life, Research Design, Shock, Septic, Logistic Models, Randomized Controlled Trials as Topic, Treatment Outcome, Pragmatic Clinical Trials as Topic

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