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

<b>Rationale:</b> Preclinical and preliminary clinical data suggest that iloprost may improve tissue perfusion in septic shock. However, its effect on organ failure remains unclear. <b>Objectives:</b> To investigate whether iloprost provides organ protection in septic shock with hypoperfusion. <b>Methods:</b> In this multicenter, double-blind, randomized controlled trial, adults with septic shock and persistent hypoperfusion (i.e., increased 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 7. Secondary outcomes included mortality at Day 28, organ support-free days by Day 28, and mean daily SOFA score. <b>Measurements and Main Results:</b> A total of 240 patients were randomized, and 236 were included in the analysis. Median (IQR) changes in SOFA score were -4 (-7 to 7) in the iloprost group and -5 (-8 to 5) in the placebo group (median difference, 1; 95% CI, 0-3; <i>P</i> = 0.12). At 28 days, 48 patients (42%) had died in the iloprost group and 47 (39%) had died in the placebo group (relative risk, 1.08; 95% CI, 0.80-1.5). The median average SOFA score was 11.2 (7.4-15.9) in the iloprost group, compared with 10.5 (6.8-16.5) in the placebo group (median difference, 0.25; 95% CI, -1.1 to 1.8). Median (95% confidence interval) between-group differences in 28-day ventilation-, vasopressor-, and renal replacement therapy-free survival days were 0 (0-0), 0 (-1 to 1), and 0 (0-0), respectively. Severe adverse events occurred in 15% of patients in the iloprost group and 7% of patients in the placebo group (<i>P</i> = 0.06). <b>Conclusions:</b> Among patients with septic shock and persistent hypoperfusion, iloprost did not reduce the severity of organ failure. Clinical trial registered with www.clinicaltrials.gov (NCT03788837) and EudraCT (2018-001709-10).

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Publication Details

Journal
American Journal of Respiratory and Critical Care Medicine
Published
2025-06-13
DOI
https://doi.org/10.1164/rccm.202410-1924oc
Citations
5
Primary Topic
Sepsis Diagnosis and Treatment
Type
article
Field-Weighted Citation Impact
6.77
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article

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

Romain Sonneville, Philippe Guerci, Julien Pottecher, Damien Barraud et al.
5 citations
American Journal of Respiratory and Critical Care Medicine
Sepsis Diagnosis and Treatment
6.77
article

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

Romain Sonneville, Philippe Guerci, Julien Pottecher, Damien Barraud, William Juguet, Adrien Auvet, Laurent Lefèbvre, Sigismond Lasocki, Antoine Kimmoun, Matthieu Legrand, Olivier Ellrodt, François Dépret, Hafid Ait‐Oufella, Guillaume Géri, David Chen, Matthieu Jamme, Stanislas Abrard, Marc Léone, Edouard Jullien, Fanny Vardon‐Bounes, Éric Vicaut, Anne-Laure Fedou, Samuel Gaugain, Jean-Michel Constantin, Juliette Audibert, Gaëtan Plantefève, Yves Poncelin de Raucourt
article en
5 citations

Abstract

<b>Rationale:</b> Preclinical and preliminary clinical data suggest that iloprost may improve tissue perfusion in septic shock. However, its effect on organ failure remains unclear. <b>Objectives:</b> To investigate whether iloprost provides organ protection in septic shock with hypoperfusion. <b>Methods:</b> In this multicenter, double-blind, randomized controlled trial, adults with septic shock and persistent hypoperfusion (i.e., increased 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 7. Secondary outcomes included mortality at Day 28, organ support-free days by Day 28, and mean daily SOFA score. <b>Measurements and Main Results:</b> A total of 240 patients were randomized, and 236 were included in the analysis. Median (IQR) changes in SOFA score were -4 (-7 to 7) in the iloprost group and -5 (-8 to 5) in the placebo group (median difference, 1; 95% CI, 0-3; <i>P</i> = 0.12). At 28 days, 48 patients (42%) had died in the iloprost group and 47 (39%) had died in the placebo group (relative risk, 1.08; 95% CI, 0.80-1.5). The median average SOFA score was 11.2 (7.4-15.9) in the iloprost group, compared with 10.5 (6.8-16.5) in the placebo group (median difference, 0.25; 95% CI, -1.1 to 1.8). Median (95% confidence interval) between-group differences in 28-day ventilation-, vasopressor-, and renal replacement therapy-free survival days were 0 (0-0), 0 (-1 to 1), and 0 (0-0), respectively. Severe adverse events occurred in 15% of patients in the iloprost group and 7% of patients in the placebo group (<i>P</i> = 0.06). <b>Conclusions:</b> Among patients with septic shock and persistent hypoperfusion, iloprost did not reduce the severity of organ failure. Clinical trial registered with www.clinicaltrials.gov (NCT03788837) and EudraCT (2018-001709-10).

American Journal of Respiratory and Critical Care MedicineVol. 211(7)
Université Claude Bernard Lyon 1 (FR), Mercy Medical Center (US), Université Toulouse III - Paul Sabatier (FR), Inserm (FR), City College of San Francisco (US), University of California, San Francisco (US), Université de Versailles Saint-Quentin-en-Yvelines (FR), Université Paris Cité (FR), Centre Hospitalier Universitaire de Toulouse (FR), Sorbonne Université (FR), Assistance Publique Hôpitaux de Marseille (FR), Université Sorbonne Paris Nord (FR), Sorbonne Paris Cité (FR), Assistance Publique – Hôpitaux de Paris (FR), Centre Hospitalier Régional et Universitaire de Nancy (FR), Hospices Civils de Lyon (FR), Hôpital Saint-Antoine (FR), Centre Hospitalier Intercommunal Aix-Pertuis (FR), Centre Hospitalier Intercommunal de Poissy (FR), Hôpital Fernand-Widal (FR), Les Hôpitaux de Chartres (FR), Hôpital Nord (FR), Centre Hospitalier Régional de Metz-Thionville (FR), Centre Hospitalier Universitaire de Limoges (FR), Hôpital Lariboisière (FR), Pitié-Salpêtrière Hospital (FR), Int'Air Medical (France) (FR), Hôpital Rangueil (FR), Melun Hospital (FR), Hôpital Avicenne (FR), Paris Cardiovascular Research Center (FR), Centre Hospitalier Victor Dupouy (FR), Centre Hospitalier de Dax –Côte d’Argent (FR), Hôpital Saint-Louis (FR), Hôpital Bichat-Claude-Bernard (FR), Clinique Hartmann (FR), Hôpitaux Universitaires de Strasbourg (FR), Institut des Maladies Métaboliques et Cardiovasculaires (FR), Clinique Ambroise Paré (FR), Générale de Santé (FR), Hôpital Dupuytren (FR), Hôpital Civil, Strasbourg (FR), French Clinical Research Infrastructure Network (FR), Université d'Angers (FR), Université de Strasbourg (FR), Université de Lorraine (FR)
Good health and well-being
Openalex Percentile: Top 3%
Sepsis Diagnosis and Treatment
6.77
DOISourceOpenAlex
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