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

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.

[1]  J. Higgins,et al.  Cochrane Handbook for Systematic Reviews of Interventions , 2010, International Coaching Psychology Review.

[2]  J. Fraser,et al.  Unintended Consequences: Fluid Resuscitation Worsens Shock in an Ovine Model of Endotoxemia , 2018, American journal of respiratory and critical care medicine.

[3]  Rinaldo Bellomo,et al.  Liberal Versus Restrictive Intravenous Fluid Therapy for Early Septic Shock: Rationale for a Randomized Trial. , 2018, Annals of emergency medicine.

[4]  J. Laake,et al.  No firm evidence that lack of blinding affects estimates of mortality in randomized clinical trials of intensive care interventions: a systematic review and meta-analysis. , 2018, Journal of clinical epidemiology.

[5]  A. Delaney,et al.  Low-dose corticosteroids for adult patients with septic shock: a systematic review with meta-analysis and trial sequential analysis , 2018, Intensive Care Medicine.

[6]  M. Cecconi,et al.  Expert statement for the management of hypovolemia in sepsis , 2018, Intensive Care Medicine.

[7]  Walter Verbrugghe,et al.  Maintenance fluid therapy and fluid creep impose more significant fluid, sodium, and chloride burdens than resuscitation fluids in critically ill patients: a retrospective study in a tertiary mixed ICU population , 2018, Intensive Care Medicine.

[8]  M. Collet,et al.  Development and internal validation of the Simplified Mortality Score for the Intensive Care Unit (SMS‐ICU) , 2018, Acta anaesthesiologica Scandinavica.

[9]  Julian P T Higgins,et al.  Association Between Risk-of-Bias Assessments and Results of Randomized Trials in Cochrane Reviews: The ROBES Meta-Epidemiologic Study , 2017, American journal of epidemiology.

[10]  G. Bernard,et al.  Effect of an Early Resuscitation Protocol on In-hospital Mortality Among Adults With Sepsis and Hypotension: A Randomized Clinical Trial , 2017, JAMA.

[11]  J. Wetterslev,et al.  Lower vs. higher fluid volumes in sepsis—protocol for a systematic review with meta‐analysis , 2017, Acta anaesthesiologica Scandinavica.

[12]  Alan E. Jones,et al.  Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016 , 2017, Intensive Care Medicine.

[13]  J. Marshall,et al.  Conservative fluid management or deresuscitation for patients with sepsis or acute respiratory distress syndrome following the resuscitation phase of critical illness: a systematic review and meta-analysis , 2017, Intensive Care Medicine.

[14]  Jørn Wetterslev,et al.  Restricting volumes of resuscitation fluid in adults with septic shock after initial management: the CLASSIC randomised, parallel-group, multicentre feasibility trial , 2016, Intensive Care Medicine.

[15]  Shock treatment in a cohort of Scandinavian intensive care units in 2014 , 2016, Acta anaesthesiologica Scandinavica.

[16]  J. Takala,et al.  Control groups in recent septic shock trials: a systematic review , 2016, Intensive Care Medicine.

[17]  R. Bellomo,et al.  The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). , 2016, JAMA.

[18]  M. Cecconi,et al.  Fluid challenges in intensive care: the FENICE study , 2015, Intensive Care Medicine.

[19]  J. Vincent,et al.  A positive fluid balance is an independent prognostic factor in patients with sepsis , 2015, Critical Care.

[20]  Per Winkel,et al.  Count Data Analysis in Randomised Clinical Trials , 2015 .

[21]  V. Mok,et al.  Montreal Cognitive Assessment 5-Minute Protocol Is a Brief, Valid, Reliable, and Feasible Cognitive Screen for Telephone Administration , 2015, Stroke.

[22]  P. Marik,et al.  Fluid overload, de-resuscitation, and outcomes in critically ill or injured patients: a systematic review with suggestions for clinical practice. , 2014, Anaesthesiology intensive therapy.

[23]  G. Bernard,et al.  Simplified Severe Sepsis Protocol: A Randomized Controlled Trial of Modified Early Goal–Directed Therapy in Zambia* , 2014, Critical care medicine.

[24]  V. Pettilä,et al.  Lower versus higher hemoglobin threshold for transfusion in septic shock. , 2014, The New England journal of medicine.

[25]  Qinghui Zhou,et al.  [Recommendations for the conduct, reporting, editing and publication of scholarly work in medical journals]. , 2014, Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology.

[26]  Mohit Bhandari,et al.  Blinded interpretation of study results can feasibly and effectively diminish interpretation bias. , 2014, Journal of clinical epidemiology.

[27]  Claude Guerin,et al.  High versus low blood-pressure target in patients with septic shock. , 2014, The New England journal of medicine.

[28]  R. Bellomo,et al.  Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000-2012. , 2014, JAMA.

[29]  Andrew D Bersten,et al.  Post Resusicitation Fluid Boluses in Severe Sepsis or Septic Shock: Prevalence and Efficacy (Price Study) , 2013, Shock.

[30]  Statistics Notes: Missing outcomes in randomised trials , 2013, BMJ.

[31]  D. Rennie,et al.  SPIRIT 2013 statement: defining standard protocol items for clinical trials. , 2013, Annals of internal medicine.

[32]  J. Kellum,et al.  Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1) , 2013, Critical Care.

[33]  A structured framework for assessing sensitivity to missing data assumptions in longitudinal clinical trials , 2013, Pharmaceutical statistics.

[34]  C. Gudex,et al.  Measurement properties of the EQ-5D-5L compared to the EQ-5D-3L across eight patient groups: a multi-country study , 2012, Quality of Life Research.

[35]  Ethan M Balk,et al.  Influence of Reported Study Design Characteristics on Intervention Effect Estimates From Randomized, Controlled Trials , 2012, Annals of Internal Medicine.

[36]  J. Tenhunen,et al.  Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis. , 2012, The New England journal of medicine.

[37]  Taka-aki Nakada,et al.  Normal-Range Blood Lactate Concentration in Septic Shock Is Prognostic and Predictive , 2012, Shock.

[38]  B. Kahan,et al.  Improper analysis of trials randomised using stratified blocks or minimisation , 2012, Statistics in medicine.

[39]  K. Maitland,et al.  Mortality after fluid bolus in African children with severe infection. , 2011, The New England journal of medicine.

[40]  P. Böelle,et al.  Mottling score predicts survival in septic shock , 2011, Intensive Care Medicine.

[41]  Taka-aki Nakada,et al.  Fluid resuscitation in septic shock: A positive fluid balance and elevated central venous pressure are associated with increased mortality* , 2011, Critical care medicine.

[42]  J. Higgins.  Cochrane handbook for systematic reviews of interventions. Version 5.1.0 [updated March 2011]. The Cochrane Collaboration , 2011 .

[43]  G. Antes,et al.  CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials , 2011 .

[44]  Per Kragh Andersen,et al.  Regression with Linear Predictors , 2010 .

[45]  D. Moher,et al.  CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials , 2010, Journal of clinical epidemiology.

[46]  Gordon R Bernard,et al.  Comparison of two fluid-management strategies in acute lung injury. , 2006, The New England journal of medicine.

[47]  V. Pettilä,et al.  Hemodynamic variables related to outcome in septic shock , 2005, Intensive Care Medicine.

[48]  J. Schafer,et al.  Missing data: our view of the state of the art. , 2002, Psychological methods.

[49]  International conference on harmonisation; guidance on statistical principles for clinical trials; availability--FDA. Notice. , 1998, Federal register.

[50]  N. Black.  CONSORT , 1996, The Lancet.

[51]  P. Gøtzsche,et al.  Blinding during data analysis and writing of manuscripts. , 1996, Controlled clinical trials.

[52]  R. Little.  A Test of Missing Completely at Random for Multivariate Data with Missing Values , 1988 .

[53]  K. K. Lan,et al.  Discrete sequential boundaries for clinical trials , 1983 .