Iloprost for the Treatment of Severe Septic Shock with Persistent Hypoperfusion: A Double-Blind, Randomized Controlled Trial

Preclinical and preliminary clinical data suggest that Iloprost may improve tissue perfusion in septic shock. However, its effect on organ failure remains unclear. In this multicenter, double-blind, randomized controlled trial, adults with septic shock and persistent hypoperfusion (i.e. elevated capillary refill time and/or skin mottling) were randomized to receive a 48-hour intravenous infusion of Iloprost or placebo. The primary outcome was the change in the Sequential Organ Failure Assessment (SOFA) score from randomization to day seven. Secondary outcomes included mortality at day 28, organ-support-free days by day 28, and mean daily SOFA score. A total of 240 patients were randomized, and 236 were included in the analysis. The median [IQR] delta of SOFA score was -4 [-7, 7] in the Iloprost group versus -5 [-8, 5] in the placebo group (median difference 1; 95% CI, 0 to 3; P=0.12). At 28 days, 48 (42%) patients had died in the Iloprost group and 47 (39%) patients in the placebo group (relative risk, 1.08; 95% CI, 0.80 to 1.5). The median of the average SOFA score was 11.2 [7.4, 15.9] in the Iloprost versus 10.5 [6.8, 16.5] in the placebo group (median difference 0.25; 95% CI, -1.1 to 1.8). Median (95% CI) between groups differences in 28-day ventilation, vasopressors and renal replacement therapy-free survival days were respectively 0 (0 to 0), 0 (-1 to 1), and 0 (0 to 0). Severe adverse events occurred in 15% of patients in the Iloprost group and in 7% of patients in the placebo group (p= 0.06). Among patients with septic shock and persistent hypoperfusion, Iloprost did not reduce the severity of organ failure. Clinical trial registration available at www. gov, ID: NCT03788837.