CLOVERS (secondary analysis)
Trial question
What is the effect of initial fluid resuscitation with lactated Ringer's solution 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 = 1312
1312 patients (617 female, 695 male).
Inclusion criteria: adult patients with a suspected or confirmed infection and hypotension caused by sepsis.
Key exclusion criteria: pre-randomization fluid administration < 95% lactated Ringer's solution or 0.9% saline; receipt of combination fluids.
Interventions
N=622 lactated Ringer's solution (lactated Ringer's solution as initial fluid resuscitation).
N=690 normal saline (0.9% sodium chloride as initial fluid resuscitation).
Primary outcome
Rate of death before home discharge by day 90
12.2%
15.9%
15.9 %
11.9 %
8.0 %
4.0 %
0.0 %
Lactated Ringer's
solution
Normal
saline
Significant
decrease ▼
NNT = 27
Significant decrease in the rate of death before home discharge by day 90 (12.2% vs. 15.9%; HR 0.71, 95% CI 0.51 to 0.99).
Secondary outcomes
Significant increase in mean hospital-free days by 28 days (16.6 days vs. 15.4 days; MD 1.6, 95% CI 0.4 to 2.8).
No significant difference in mean organ support-free days at 28 days (24.2 days vs. 23.5 days; MD 0.6, 95% CI -0.4 to 1.5).
No significant difference in mean ventilator-free days at 28 days (23.7 days vs. 22.7 days; MD 0.9, 95% CI -0.2 to 2).
Safety outcomes
No significant difference in AKI within 7 days.
Conclusion
In adult patients with a suspected or confirmed infection and hypotension caused by sepsis, lactated Ringer's solution was superior to normal saline with respect to the rate of death before home discharge by day 90.
Reference
Georg Gelbenegger, Nathan I Shapiro, Markus Zeitlinger et al. Lactated Ringer's or Normal Saline for Initial Fluid Resuscitation in Sepsis-Induced Hypotension. Crit Care Med. 2025 Feb 19. Online ahead of print.
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