FX06 to rescue SARS-CoV-2-induced acute respiratory distress syndrome: a randomized clinical trial

Critical Care

Research

Stéphane Germain¹  Jan Hayon²  Guillaume Franchineau³  Loïc Le Guennec⁴  Pierre Asfar⁵  Lucie Le Fèvre⁶  Thomas Frapard⁷  Emmanuelle Guérin⁷  Nicolas Bréchot⁸  Charles-Edouard Luyt⁹  Alain Combes⁹  David Hajage^1,10  Lisa Belin^1,10  Mamadou Hassimiou Diallo^1,10 

[1] Center for Interdisciplinary Research in Biology, Collège de France, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale (INSERM), Université PSL, Paris, France;Intensive Care Unit, Centre Hospitalier Intercommunal de Poissy–Saint-Germain-en-Laye, Poissy, France;Intensive Care Unit, Centre Hospitalier Intercommunal de Poissy–Saint-Germain-en-Laye, Poissy, France;INSERM U1018, Centre de Recherche en Épidémiologie Et Santé Des Populations (CESP), Equipe “Rein et Cœur”, Université Paris Saclay, Villejuif, France;Médecine Intensive-Réanimation Neurologique, Hôpital Pitié–Salpêtrière, APHP, Paris, France;Sorbonne Universités, Paris, France;Service de Médecine Intensive-Réanimation et Médecine Hyperbare, Centre Universitaire Hospitalier d’Angers, Angers, France;Service de Médecine Intensive-Réanimation, Institut de Cardiologie, Assistance Publique–Hôpitaux de Paris (APHP), Hôpital Pitié–Salpêtrière, Paris, France;Service de Médecine Intensive-Réanimation, Institut de Cardiologie, Assistance Publique–Hôpitaux de Paris (APHP), Hôpital Pitié–Salpêtrière, Paris, France;Center for Interdisciplinary Research in Biology, Collège de France, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale (INSERM), Université PSL, Paris, France;Service de Médecine Intensive-Réanimation, Institut de Cardiologie, Assistance Publique–Hôpitaux de Paris (APHP), Hôpital Pitié–Salpêtrière, Paris, France;Center for Interdisciplinary Research in Biology, Collège de France, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale (INSERM), Université PSL, Paris, France;Service de Médecine Intensive-Réanimation, Hôpital Européen Georges-Pompidou, APHP, Paris, France;Université Paris Cité, Paris, France;Service de Médecine Intensive-Réanimation, Institut de Cardiologie, Assistance Publique–Hôpitaux de Paris (APHP), Hôpital Pitié–Salpêtrière, Paris, France;Sorbonne Université INSERM-UMRS 1166, Institute of Cardiometabolism and Nutrition, Paris, France;Sorbonne Université, INSERM, Institut Pierre Louis d’ Epidémiologie et de Santé Publique, AP-HP, Hôpital Pitié Salpêtrière, Département de Santé Publique, Unité de Recherche Clinique PSL-CFX, CIC-1901, 75013, Paris, France;

关键词: FX06;    Vascular leakage;    Endothelial hyperpermeability;    Acute respiratory distress syndrome;    SARS-CoV-2;   

DOI  :  10.1186/s13054-023-04616-1

 received in 2023-02-09, accepted in 2023-08-16,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundVascular leakage is a major feature of acute respiratory distress syndrome (ARDS). We aimed to evaluate the efficacy of FX06, a drug under development that stabilizes interendothelial cell junctions, at reducing vascular leakage during SARS-CoV-2-induced ARDS.MethodsThis multicenter, double-blinded, randomized trial included adults with COVID-19-associated ARDS who had received invasive mechanical ventilation for < 5 days and were randomized to receive either intravenous FX06 (400 mg/d, for 5 days) or its vehicle as placebo. The primary endpoint was the lowering—from day 1 to day 7—of the transpulmonary thermodilution-derived extravascular lung-water index (EVLWi).ResultsTwenty-five patients were randomized to receive FX06 and 24 the placebo. Although EVLWi was elevated at baseline (median [IQR] 15.6 mL/kg [13.5; 18.5]), its declines from day 1 to day 7 were comparable for FX06 recipients and controls (respectively, − 1.9 [− 3.3; − 0.5] vs. − 0.8 [− 5.5; − 1.1] mL/kg; estimated effect − 0.8 [− 3.1; + 2.4], p = 0.51). Cardiac indexes, pulmonary vascular permeability indexes, and fluid balances were also comparable, as were PaO2/FiO2 ratios and durations of mechanical ventilation. Adverse event rates were similar for the 2 groups, although more FX06 recipients developed ventilator-associated pneumonia (16/25 (64%) vs. 6/24 (24%), p = 0.009).ConclusionsIn this unique-dosing–regimen study, FX06 did not lower SARS-CoV-2-induced pulmonary vascular leakage. Future investigations will need to evaluate its efficacy at earlier times during the disease or using other regimens.Trial registration NCT04618042. Registered 5 November 2020.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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