COMBAT-SHINE
Trial question
What is the role of iloprost in patients with septic shock and severe endotheliopathy?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
38.0% female
62.0% male
N = 278
278 patients (107 female, 171 male).
Inclusion criteria: adult patients in the ICU with septic shock and endotheliopathy.
Key exclusion criteria: screening > 12 hours after diagnosis of septic shock; inclusion in another clinical trial with prostacyclin within 90 days; pregnancy; life-threatening bleeding; known severe HF; suspected acute coronary syndrome.
Interventions
N=142 iloprost (intravenous infusion of 1 ng/kg/min for 72 hours).
N=136 placebo (intravenous infusion of placebo for 72 hours).
Primary outcome
Mean daily Sequential Organ Failure Assessment score in intensive care unit up to day 90
10.6 points
10.5 points
10.6 points
7.9 points
5.3 points
2.6 points
0.0 points
Iloprost
Placebo
No significant
difference ↔
No significant difference in mean daily SOFA score in the ICU up to day 90 (10.6 points vs. 10.5 points; MD 0.2, 95% CI -0.8 to 1.2).
Secondary outcomes
No significant difference in death at day 28 (49% vs. 44%; RR 1.13, 95% CI 0.88 to 1.46).
No significant difference in death at day 90 (57% vs. 51%; RR 1.12, 95% CI 0.91 to 1.4).
No significant difference in median days alive without vasopressors at day 90 (16 days vs. 53 days; MD 37, 95% CI -28 to 67).
Safety outcomes
No significant difference in serious adverse events.
Conclusion
In adult patients in the ICU with septic shock and endotheliopathy, iloprost was not superior to placebo with respect to mean daily SOFA score in the ICU up to day 90.
Reference
Morten H Bestle, Jakob Stensballe, Theis Lange et al. Iloprost and Organ Dysfunction in Adults With Septic Shock and Endotheliopathy: A Randomized Clinical Trial. JAMA Netw Open. 2024 Sep 3;7(9):e2432444.
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