FX06 to rescue SARS-CoV-2-induced acute respiratory distress syndrome: a randomized clinical trial
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 multic...
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| Format: | Article |
| Language: | English |
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BMC
2023-08-01
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| Series: | Critical Care |
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| Online Access: | https://doi.org/10.1186/s13054-023-04616-1 |
| _version_ | 1797699355488026624 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Emmanuelle Guérin |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T04:06:52Z |
| format | Article |
| id | doaj.art-7d0ee03f3545421d8d48646355d062b0 |
| institution | Directory Open Access Journal |
| issn | 1364-8535 |
| language | English |
| last_indexed | 2024-03-12T04:06:52Z |
| publishDate | 2023-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Critical Care |
| spelling | doaj.art-7d0ee03f3545421d8d48646355d062b02023-09-03T11:16:13ZengBMCCritical Care1364-85352023-08-0127111110.1186/s13054-023-04616-1FX06 to rescue SARS-CoV-2-induced acute respiratory distress syndrome: a randomized clinical trialEmmanuelle Guérin0Lisa Belin1Guillaume Franchineau2Loïc Le Guennec3David Hajage4Mamadou Hassimiou Diallo5Thomas Frapard6Lucie Le Fèvre7Charles-Edouard Luyt8Alain Combes9Stéphane Germain10Jan Hayon11Pierre Asfar12Nicolas Bréchot13Service de Médecine Intensive-Réanimation, Institut de Cardiologie, Assistance Publique–Hôpitaux de Paris (APHP), Hôpital Pitié–SalpêtrièreSorbonne 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-1901Intensive Care Unit, Centre Hospitalier Intercommunal de Poissy–Saint-Germain-en-LayeMédecine Intensive-Réanimation Neurologique, Hôpital Pitié–Salpêtrière, APHPSorbonne 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-1901Sorbonne 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-1901Service de Médecine Intensive-Réanimation, Institut de Cardiologie, Assistance Publique–Hôpitaux de Paris (APHP), Hôpital Pitié–SalpêtrièreService de Médecine Intensive-Réanimation, Institut de Cardiologie, Assistance Publique–Hôpitaux de Paris (APHP), Hôpital Pitié–SalpêtrièreService de Médecine Intensive-Réanimation, Institut de Cardiologie, Assistance Publique–Hôpitaux de Paris (APHP), Hôpital Pitié–SalpêtrièreService de Médecine Intensive-Réanimation, Institut de Cardiologie, Assistance Publique–Hôpitaux de Paris (APHP), Hôpital Pitié–SalpêtrièreCenter 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 PSLIntensive Care Unit, Centre Hospitalier Intercommunal de Poissy–Saint-Germain-en-LayeService de Médecine Intensive-Réanimation et Médecine Hyperbare, Centre Universitaire Hospitalier d’AngersService de Médecine Intensive-Réanimation, Institut de Cardiologie, Assistance Publique–Hôpitaux de Paris (APHP), Hôpital Pitié–SalpêtrièreAbstract 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.https://doi.org/10.1186/s13054-023-04616-1FX06Vascular leakageEndothelial hyperpermeabilityAcute respiratory distress syndromeSARS-CoV-2 |
| spellingShingle | 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 FX06 to rescue SARS-CoV-2-induced acute respiratory distress syndrome: a randomized clinical trial Critical Care FX06 Vascular leakage Endothelial hyperpermeability Acute respiratory distress syndrome SARS-CoV-2 |
| title | FX06 to rescue SARS-CoV-2-induced acute respiratory distress syndrome: a randomized clinical trial |
| title_full | FX06 to rescue SARS-CoV-2-induced acute respiratory distress syndrome: a randomized clinical trial |
| title_fullStr | FX06 to rescue SARS-CoV-2-induced acute respiratory distress syndrome: a randomized clinical trial |
| title_full_unstemmed | FX06 to rescue SARS-CoV-2-induced acute respiratory distress syndrome: a randomized clinical trial |
| title_short | FX06 to rescue SARS-CoV-2-induced acute respiratory distress syndrome: a randomized clinical trial |
| title_sort | fx06 to rescue sars cov 2 induced acute respiratory distress syndrome a randomized clinical trial |
| topic | FX06 Vascular leakage Endothelial hyperpermeability Acute respiratory distress syndrome SARS-CoV-2 |
| url | https://doi.org/10.1186/s13054-023-04616-1 |
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