Iloprost Ineffective for Organ Dysfunction in Septic Shock

TOPLINE:

Compared with placebo, a 72-hour infusion of 1 ng/kg/min iloprost does not improve outcomes or reduce the severity of organ failure among patients admitted to the intensive care unit (ICU) with septic shock and high soluble thrombomodulin levels.

METHODOLOGY:

• Researchers conducted a double-blind randomized clinical trial (COMBAT-SHINE) at six hospitals in Denmark that included 279 adults admitted to the ICU with septic shock and severe endotheliopathy (high soluble thrombomodulin levels).
• Participants (median age, 69 years; 62% men) were randomly assigned in a 1:1 ratio to intravenously receive either iloprost (1 ng/kg/min) or placebo for 72 hours.
• The primary outcome was the mean daily modified Sequential Organ Failure Assessment (SOFA) score, assessing respiration, coagulation, and liver, cardiovascular, and kidney functions in the ICU up to day 90.
• The secondary outcomes included 28- and 90-day mortality rates; the number of days alive without vasopressors, mechanical ventilation, or kidney replacement therapy in the ICU at 90 days; and the number of patients with one or more serious adverse reactions or events within the first 7 days.

TAKEAWAY:

• The mean daily SOFA score with iloprost treatment was not significantly lower than that with placebo treatment ( adjusted mean difference, 0.2; P =.70).
• Mortality rates at 90 days were 57% for the iloprost group and 51% for the placebo group (P =.33).
• No significant differences were found among the two groups in the number of days alive without vasopressors, mechanical ventilation, or kidney replacement therapy at 90 days.
• At least one prespecified serious adverse event occurred 18% patients in the iloprost group and 15% patients in the placebo group (P =.52).

IN PRACTICE:

“In this randomized clinical trial of adults in the ICU with septic shock and severe endotheliopathy, infusion of iloprost, 1 ng/kg/min, for 72 hours did not reduce mean daily SOFA scores compared with placebo. In a clinical context, administration of iloprost will be unlikely to improve outcome in these patients,” the authors wrote.

SOURCE:

The study was led by Morten H. Bestle, MD, PhD, Department of Anesthesia and Intensive Care, Copenhagen University Hospital-North Zealand, Hillerød, Denmark. It was published online on September 11, 2024, in JAMA Network Open.

LIMITATIONS:

The study was limited by the low dose of iloprost administered. Screening was performed for up to 12 hours after the diagnosis of septic shock, which may have delayed the intervention. The study was conducted only in Denmark, limiting generalizability. The sample size calculation was based on data from a trial with a lower mean daily SOFA score than the one observed in the control group. Moreover, the trial was stopped early for futility based on organ dysfunction outcomes, and SOFA scores may not be the optimal outcome for this type of trial.

DISCLOSURES:

The COMBAT-SHINE trial was funded by Innovation Fund Denmark and the Danish Agency for Science and Higher Education, Copenhagen. Several authors reported receiving personal fees, grants, and contract research funds from various foundations, pharmaceutical companies, and institutions. One author reported holding patents related to the use of prostacyclin in patients with septic shock and endotheliopathy. Detailed disclosures are provided in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.