BACKGROUND:~Septic shock is common, often lethal, costly, and associated with prolonged suffering among survivors and relatives. Traditionally, intravenous (IV) fluids are used to optimise the circulation, and the use of higher volumes is recommended by international guidelines. There is, however, no high-quality evidence to support this. In contrast, data from cohort studies, small trials and systematic reviews in sepsis and large trials in other settings and patient groups suggest potential benefits from restriction of IV fluids in patients with septic shock.~OBJECTIVES:~The aim of the CLASSIC trial is to assess the benefits and harms of IV fluid restriction vs. standard care on patient-important outcome measures in adult intensive care unit (ICU) patients with septic shock.~DESIGN:~CLASSIC is an international, multicentre, parallel-grouped, open-labelled, centrally randomised, stratified, outcome assessor- and analyst-blinded trial.~POPULATION:~Adult ICU patients who have septic shock and have received at least 1 L of IV fluid in the last 24-hours.~EXPERIMENTAL INTERVENTION:~In the IV fluid restriction group no IV fluids should be given in the ICU unless extenuating circumstances occur, including signs of severe hypoperfusion, overt fluid loss or a failing GI tract with a total fluid input of less than 1 L per day. In these circumstances, IV fluid may be given in measured amounts.~CONTROL INTERVENTION:~In the standard care group there will be no upper limit for the use of IV fluids.~OUTCOMES:~The primary outcome is 90-day mortality; secondary outcomes are serious adverse events in the ICU (ischemic events or severe acute kidney injury); serious adverse reactions in the ICU; days alive without life support at day 90; days alive and out of hospital at day 90 and mortality, health-related quality of life and cognitive function at 1-year.~TRIAL SIZE:~A total of 1554 participants will be randomised to allow the detection of a 15% relative risk reduction (7% absolute) in the restrictive vs. standard care group in 90-day mortality with a power of 80%.
The purpose of this trial is to assess patient important benefits and harms of IV fluid restriction vs. standard care fluid therapy in patients with septic shock.