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 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 (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.
Original statement on NHLBI decision to end phase 3 sepsis trial early
Feb. 9, 2022
Enrollment in a National Institutes of Health-supported trial with 1,566 patients being treated for sepsis at 51 U.S. medical centers ended early due to a lack of significant difference observed between two 24-hour treatment strategies.
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 (PETAL) network and funded by the National Heart, Lung, and Blood Institute (NHLBI). In this phase 3 study (NCT03434028), researchers randomly assigned patients being treated for sepsis with low blood pressure after initial treatment into one of two arms of the trial. The first arm preferentially used fluid infusions through an intravenous catheter to raise blood pressure before vasopressors (medications used to raise blood pressure). The second arm preferentially used vasopressors to raise blood pressure before additional intravenous fluids. Both approaches are currently used to support patients with sepsis. The goal of this study was to determine if the order of treatments would improve survival, which was measured over 90 days.
The CLOVERS trial started on March 7, 2018, and researchers planned to enroll up to 2,320 patients. After a scheduled interim analysis on Feb. 2, 2022, an independent data and safety monitoring board found that outcomes were similar in both arms and that further enrollment was unlikely to change the result. They also found no concerns regarding patient safety.
The researchers note that the findings are important since they show that both approaches to treating sepsis have similar outcomes. They will continue patient follow-up according to the protocol, including the completion of data collection on all patients already enrolled in the trial. Formal analyses of study data are underway and findings are forthcoming. Researchers plan to share findings from the trial through presentations at scientific meetings and by publishing results from the study in peer-reviewed journals.
Sepsis can produce immediate shock-like symptoms and affect multiple organs and systems following a bacterial or viral infection. Common symptoms include a sudden rise in heart rate or drop in blood pressure; chills, such as fever, shivering, or feeling very cold; confusion or disorientation; shortness of breath; extreme pain or discomfort; and clammy or sweaty skin.
According to the Centers for Disease Control and Prevention, sepsis affects 1.7 million Americans and accounts for more than 250,000 U.S. deaths each year. Older adults, young infants, people with compromised immune function, and patients recently hospitalized are at greater risk for septic-like shock, the body’s extreme response to infection.
Through PETAL, NHLBI-supported researchers at 12 clinical centers and a coordinating center are studying ways to prevent and treat sudden lung injuries and acute respiratory distress syndrome that can occur following sepsis.