FX06 to rescue SARS-CoV-2-induced acute respiratory distress syndrome: a randomized clinical trial
Emmanuelle Guérin,
Lisa Belin,
Guillaume Franchineau,
Loïc Le Guennec,
David Hajage,
Mamadou Hassimiou Diallo,
Thomas Frapard,
Lucie Le Fèvre,
Charles-Edouard Luyt,
Alain Combes,
Stéphane Germain,
Jan Hayon,
Pierre Asfar,
Nicolas Bréchot
Affiliations
Emmanuelle Guérin
Service de Médecine Intensive-Réanimation, Institut de Cardiologie, Assistance Publique–Hôpitaux de Paris (APHP), Hôpital Pitié–Salpêtrière
Lisa Belin
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
Guillaume Franchineau
Intensive Care Unit, Centre Hospitalier Intercommunal de Poissy–Saint-Germain-en-Laye
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
Mamadou Hassimiou Diallo
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
Thomas Frapard
Service de Médecine Intensive-Réanimation, Institut de Cardiologie, Assistance Publique–Hôpitaux de Paris (APHP), Hôpital Pitié–Salpêtrière
Lucie Le Fèvre
Service de Médecine Intensive-Réanimation, Institut de Cardiologie, Assistance Publique–Hôpitaux de Paris (APHP), Hôpital Pitié–Salpêtrière
Charles-Edouard Luyt
Service de Médecine Intensive-Réanimation, Institut de Cardiologie, Assistance Publique–Hôpitaux de Paris (APHP), Hôpital Pitié–Salpêtrière
Alain Combes
Service de Médecine Intensive-Réanimation, Institut de Cardiologie, Assistance Publique–Hôpitaux de Paris (APHP), Hôpital Pitié–Salpêtrière
Stéphane Germain
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
Jan Hayon
Intensive Care Unit, Centre Hospitalier Intercommunal de Poissy–Saint-Germain-en-Laye
Pierre Asfar
Service de Médecine Intensive-Réanimation et Médecine Hyperbare, Centre Universitaire Hospitalier d’Angers
Nicolas Bréchot
Service de Médecine Intensive-Réanimation, Institut de Cardiologie, Assistance Publique–Hôpitaux de Paris (APHP), Hôpital Pitié–Salpêtrière
Abstract Background Vascular 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. Methods This 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). Results Twenty-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). Conclusions In 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.
