6/28/23, 12:12 AM CLOVERS Pathway Feedback Search Clinical Topics Home Studies CLOVERS CLOVERS Disease Sepsis and septic shock Trial question Is restrictive fluid strategy superior to liberal fluid strategy in patients with sepsis-induced hypotension? Study design Multi-center Open label RCT Population Characteristics of study participants 47.0% female N = 1563 53.0% male 1563 patients (737 female, 826 male) Inclusion criteria: adult patients within 4 hours of a suspected or confirmed infection and sepsis-induced hypotension Key exclusion criteria: relapse of > 4 hours of meeting the criteria for sepsis-induced hypotension; elapse of > 24 hours since presentation at the hospital; previous receipt of > 3,000 mL of intravenous fluid during this episode; presence of fluid overload; severe volume depletion from nonseptic causes Interventions N=782 restrictive fluid strategy (early vasopressors, rescue fluids permitted for prespecified indications) N=781 liberal fluid strategy (initial 2,000 mL intravenous infusion of isotonic crystalloid, followed by fluid boluses administered on the basis of clinical triggers) P i t https://web.pathway.md/studies/recInxJ2LCodMtdka 1/2 6/28/23, 12:12 AM CLOVERS Pathway Primary outcome Death from any causes before discharge home at day 90 14.9 % 14.9 14 11.2 % 7.5 % 3.7 % No significant difference 0.0 % Restrictive fluid strategy Liberal fluid strategy No significant difference in death from any causes before discharge home at day 90 (14% vs. 14.9%; ARD -0.9, 95% CI -4.4 to 2.6) Secondary outcomes No significant difference in the number of days free from organ-support therapy at 28 days (24 days vs. 23.6 days; AD 0.3 days, 95% CI -0.5 to 1.2) No significant difference in the number of days free from ventilator use at 28 days (23.4 days vs. 22.8 days; AD 0.6 days, 95% CI -0.4 to 1.6) No significant difference in the number of days free from RRT at 28 days (24.1 days vs. 23.9 days; AD 0.2 days, 95% CI -0.8 to 1.2) Safety outcomes No significant difference in serious adverse events. Conclusion In adult patients within 4 hours of a suspected or confirmed infection and sepsis-induced hypotension, restrictive fluid strategy was not superior to liberal fluid strategy with respect to death from any causes before discharge home at day 90. Reference National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Clinical Trials Network et al. Early Restrictive or Liberal Fluid Management for Sepsis-Induced Hypotension. N Engl J Med. 2023 Feb 9;388(6):499-510. Open reference URL https://web.pathway.md/studies/recInxJ2LCodMtdka 2/2