2023CLOVERSFluid strategyIn 1,563 patients with sepsis-induced hypotension after 1–3 L fluid, a restrictive-fluid strategy with early vasopressors did not change 90-day mortality compared with a liberal-fluid strategy.
2023STRESS-LHeart-rate controlIn 126 patients with tachycardic septic shock, landiolol added to standard care did not change SOFA at 14 days versus standard care alone, with a numerical mortality-harm signal.
2022CLASSICFluid strategyIn 1,554 ICU patients with septic shock after initial resuscitation, restrictive intravenous fluids did not change 90-day mortality compared with standard fluids.
2022LOVITAdjunctsIn 872 ICU patients with sepsis on vasopressors, high-dose intravenous vitamin C increased the composite of death or persistent organ dysfunction at 28 days versus placebo.
2021VICTASAdjunctsIn 501 patients with sepsis-induced respiratory or cardiovascular failure, vitamin C + thiamine + hydrocortisone did not increase ventilator- and vasopressor-free days versus placebo.
2020VITAMINSAdjunctsIn 216 patients with septic shock, hydrocortisone + vitamin C + thiamine did not increase vasopressor-free time versus hydrocortisone alone.
2019ANDROMEDA-SHOCKResuscitation targetsIn 424 patients with early septic shock, capillary-refill-time–guided resuscitation did not reduce 28-day mortality compared with lactate-guided resuscitation, but lowered SOFA at 72 hours.
2018ADRENALSteroidsIn 3,800 mechanically ventilated patients with septic shock, hydrocortisone 200 mg/day did not reduce 90-day mortality versus placebo, but accelerated shock reversal and discharge.
2018APROCCHSSSteroidsIn 1,241 patients with septic shock on vasopressors ≥6 hours, hydrocortisone + fludrocortisone reduced 90-day mortality compared with placebo.
2017ATHOS-3VasopressorsIn 321 patients with catecholamine-resistant vasodilatory shock, synthetic angiotensin II improved MAP response at 3 hours compared with placebo, without proven mortality benefit.
2016VANISHVasopressorsIn 409 patients with septic shock, early vasopressin (± hydrocortisone) did not increase kidney-failure-free days versus norepinephrine, but reduced RRT use.
2015ProMISeResuscitation bundlesIn 1,260 UK patients with early septic shock, EGDT did not reduce 90-day all-cause mortality compared with usual care, and increased ICU length of stay.
2014ProCESSResuscitation bundlesIn 1,341 patients with early septic shock, protocol-based EGDT or protocol-based standard care did not reduce 60-day in-hospital mortality compared with usual care.
2014ARISEResuscitation bundlesIn 1,600 patients with early septic shock, EGDT did not change 90-day all-cause mortality versus usual care.
2014SEPSISPAMMAP targetsIn 776 patients with septic shock, targeting MAP 80–85 mm Hg did not change 28-day mortality versus MAP 65–70 mm Hg, but reduced renal-replacement therapy in chronic hypertension.
2010SOAP IIVasopressorsIn 1,679 patients with shock, noradrenaline produced similar mortality but fewer arrhythmias compared with dopamine.
2008VASSTVasopressorsIn 778 patients with septic shock on ≥5 µg/min norepinephrine, low-dose vasopressin added to norepinephrine did not reduce 28-day mortality compared with norepinephrine alone.
2008CORTICUSSteroidsIn 499 patients with septic shock, hydrocortisone 200 mg/day did not reduce 28-day mortality versus placebo.
2001Rivers EGDTResuscitation bundlesIn 263 emergency-department patients with severe sepsis or septic shock, a 6-hour protocol targeting CVP, MAP, ScvO₂ and haematocrit reduced in-hospital mortality compared with standard care.