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

Journal: Critical care (London, England) 2023;27(1):331

PMID: 37641136

Free Full Text on BioMed Central View on PubMed

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 PaO/FiO 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.

Address: 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.; 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.; 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.; Sorbonne Université INSERM-UMRS 1166, Institute of Cardiometabolism and Nutrition, 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. [email protected].; 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. [email protected].; Service de Médecine Intensive-Réanimation, Hôpital Européen Georges-Pompidou, APHP, Paris, France. [email protected].; Université Paris Cité, Paris, France. [email protected].

DOI: 10.1186/s13054-023-04616-1

Link outs

Free resources

Full Text Sources:

Medical:

Miscellaneous:

https://assays.cancer.gov/CPTAC-438

MeSH Terms: Adult, Humans, COVID-19, SARS-CoV-2, Respiratory Distress Syndrome, Administration, Intravenous, Capillary Permeability