Iloprost fails to Improve organ function in patients with septic shock and severe endotheliopathy: JAMA

A recent clinical trial published in the Journal of American Medical Association revealed that the drug iloprost, commonly used to treat vascular conditions, does not improve organ function in patients with septic shock and severe endotheliopathy. The study was conducted across 6 hospitals in Denmark to explore whether iloprost could help reduce organ dysfunction in patients with elevated levels of soluble thrombomodulin which is a marker of endotheliopathy. However, the results showed no significant difference between the iloprost-treated group and the ones receiving a placebo.

This double-blinded trial ran from November 2019 to July 2022 and included a total of 279 adult ICU patients diagnosed with septic shock and severe endotheliopathy by plasma soluble thrombomodulin levels greater than 10 ng/mL. The patients were randomly assigned to receive either iloprost which was administered via intravenous infusion at a dosage of 1 ng/kg/min for 72 hours, or a placebo. The primary objective was to assess the impact of iloprost on the severity of organ failure which was measured by the Sequential Organ Failure Assessment (SOFA) score is a common scale used to evaluate organ dysfunction in critical care. Secondary outcomes included mortality at 90 days and the occurrence of serious adverse events or reactions.

After the interim analysis, the trial was halted for futility which indicated that the treatment was unlikely to provide any substantial benefit. The mean daily SOFA score in the ICU reflected the severity of organ dysfunction which was 10.6 in the iloprost group and 10.5 in the placebo group. The 90-day mortality rate was also similar between the groups, with 57% of patients in the iloprost group and 51% in the placebo group succumbing to their illness (adjusted relative risk: 1.12, 95% CI: 0.91-1.40, P = 0.33). Also, 18% of patients in the iloprost group faced serious adverse events when compared to 15% in the placebo group by further demonstrating no significant difference. Overall, the findings of this trial suggest that iloprost is unlikely to be beneficial for patients with septic shock and severe endotheliopathy.

Source:

Bestle, M. H., Stensballe, J., Lange, T., Clausen, N. E., Søe-Jensen, P., Pedersen, K. H., Gybel-Brask, M., Kjær, M.-B. N., Steensen, C. O., Jensen, D. B., Gärtner, R., Schønemann-Lund, M., Kristiansen, K. T., Lindhardt, A., Johansson, P. I., & Perner, A. (2024). Iloprost and Organ Dysfunction in Adults With Septic Shock and Endotheliopathy. In JAMA Network Open (Vol. 7, Issue 9, p. e2432444). American Medical Association (AMA). https://doi.org/10.1001/jamanetworkopen.2024.32444