General public

Purpose: The CLOVERS study compares two methods of increasing blood pressure in patients with dangerously low blood pressure due to a suspected infection. One method is the first provide intravenous fluids to the patient, and then use drugs such as adrenalin (called vasopressors); the other method is to use the drugs first, and then use fluids.

Trial summary:

• Study design: this is a multi-center, prospective, phase 3 randomized non-blinded interventional trial of fluid treatment strategies in the first 24 hours for patients with sepsis-induced hypotension (dangerously low blood pressure from a suspected infection).
• Purpose: to determine the impact of a restrictive fluids strategy (vasopressors first followed by rescue fluids) as compared to a liberal fluid strategy (fluids first followed by rescue vasopressors) on 90-day in-hospital mortality in patients with sepsis-induced hypotension.
• Sample size: this trial will enroll up to 2,230 subjects from PETAL network emergency rooms.

Update January 21, 2023

Findings from a randomized, non-blinded, phase 3 clinical trial supported by the National Institutes of Health found no significant difference in 90-day mortality rates, nor safety concerns, after providing patients with one of two common treatment strategies for sepsis. The findings were published in the New England Journal of Medicine (No differences found between liberal or restrictive fluid treatment strategies for septic-inducted hypotension) and were simultaneously presented at the 2023 Critical Care Congress.

The Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis (CLOVERS) trial is a randomized clinical trial conducted by the Prevention and Early Treatment of Acute Lung Injury external link (PETAL) network and funded by the National Heart, Lung, and Blood Institute (NHLBI). Enrollment in the trial ended in February 2022 due to a lack of significant difference observed between the two 24-hour strategies.

The trial, which included 1,563 patients from 60 medical centers, also found no significant differences in 90-day survival rates or other measures of recovery, such as length of hospital stay, among adults assigned to a restrictive or liberal fluid-management treatment strategy for a sudden drop in blood pressure due to sepsis.