CLOVERS (original research)
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
53.0% male
N = 1563
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).
Primary outcome
Death from any causes before discharge home at day 90
14%
14.9%
14.9 %
11.2 %
7.5 %
3.7 %
0.0 %
Restrictive fluid
strategy
Liberal fluid
strategy
No significant
difference ↔
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.
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