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

DOI record: { "DOI": "10.1186/s13054-023-04616-1", "ISSN": [ "1364-8535" ], "URL": "http://dx.doi.org/10.1186/s13054-023-04616-1", "abstract": "<jats:title>Abstract</jats:title><jats:sec>\n <jats:title>Background</jats:title>\n <jats:p>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.</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Methods</jats:title>\n <jats:p>This multicenter, double-blinded, randomized trial included adults with COVID-19-associated ARDS who had received invasive mechanical ventilation for &lt; 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).</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Results</jats:title>\n <jats:p>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], <jats:italic>p</jats:italic> = 0.51). Cardiac indexes, pulmonary vascular permeability indexes, and fluid balances were also comparable, as were PaO<jats:sub>2</jats:sub>/FiO<jats:sub>2</jats:sub> 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%), <jats:italic>p</jats:italic> = 0.009).</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Conclusions</jats:title>\n <jats:p>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.</jats:p>\n <jats:p><jats:italic>Trial registration</jats:italic> NCT04618042. Registered 5 November 2020.</jats:p>\n </jats:sec>", "alternative-id": [ "4616" ], "article-number": "331", "assertion": [ { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "Received", "name": "received", "order": 1, "value": "9 February 2023" }, { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "Accepted", "name": "accepted", "order": 2, "value": "16 August 2023" }, { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "First Online", "name": "first_online", "order": 3, "value": "29 August 2023" }, { "group": { "label": "Declarations", "name": "EthicsHeading" }, "name": "Ethics", "order": 1 }, { "group": { "label": "Ethics approval and consent to participate", "name": "EthicsHeading" }, "name": "Ethics", "order": 2, "value": "The independent ethics review board CPP Ouest VI, Brest, France, approved the trial protocol (CPP 1306-EudraCT 2020-002056-20/RIPH 20.06.15.56627). The trial was conducted in accordance with the ethical principles of the Declaration of Helsinki, the International Conference on Harmonisation–Good Clinical Practice (ICH-GCP) guideline, the Quality Management Standards for Drug Clinical Trials of the French Food and Drug Administration (ANSM, Agence Nationale de Sécurité du Médicament et des Produits de Santé). According to the specifications of emergency consent, randomization without a close relative or surrogate consent could be performed, but informed consent by the patient or patient’s relatives was obtained for all patients." }, { "group": { "label": "Consent for publication", "name": "EthicsHeading" }, "name": "Ethics", "order": 3, "value": "Not applicable." }, { "group": { "label": "Competing interests", "name": "EthicsHeading" }, "name": "Ethics", "order": 4, "value": "Dr Bréchot is on the F4-Pharma advisory board, without any financial competing interest. He received a grant from the French Ministry of Health for another study evaluating FX06. He receives fees from Findimmune, outside the scope of this study. Dr Luyt reported receiving grants from French Ministry of Health during the conduct of the study; personal fees from Bayer Healthcare, Carmat, Faron, Merck Sharp & Dohme, ThermoFisher Brahms, and BioMérieux, outside the submitted work. Dr. Combes reports receiving grant support and lecture fees from Maquet and Baxter, and consulting fees from Hemovent." } ], "author": [ { "affiliation": [], "family": "Guérin", "given": "Emmanuelle", "sequence": "first" }, { "affiliation": [], "family": "Belin", "given": "Lisa", "sequence": "additional" }, { "affiliation": [], "family": "Franchineau", "given": "Guillaume", "sequence": "additional" }, { "affiliation": [], "family": "Le Guennec", "given": "Loïc", "sequence": "additional" }, { "affiliation": [], "family": "Hajage", "given": "David", "sequence": "additional" }, { "affiliation": [], "family": "Diallo", "given": "Mamadou Hassimiou", "sequence": "additional" }, { "affiliation": [], "family": "Frapard", "given": "Thomas", "sequence": "additional" }, { "affiliation": [], "family": "Le Fèvre", "given": "Lucie", "sequence": "additional" }, { "affiliation": [], "family": "Luyt", "given": "Charles-Edouard", "sequence": "additional" }, { "affiliation": [], "family": "Combes", "given": "Alain", "sequence": "additional" }, { "affiliation": [], "family": "Germain", "given": "Stéphane", "sequence": "additional" }, { "affiliation": [], "family": "Hayon", "given": "Jan", "sequence": "additional" }, { "affiliation": [], "family": "Asfar", "given": "Pierre", "sequence": "additional" }, { "affiliation": [], "family": "Bréchot", "given": "Nicolas", "sequence": "additional" } ], "container-title": "Critical Care", "container-title-short": "Crit Care", "content-domain": { "crossmark-restriction": false, "domain": [ "link.springer.com" ] }, "created": { "date-parts": [ [ 2023, 8, 29 ] ], "date-time": "2023-08-29T02:01:44Z", "timestamp": 1693274504000 }, "deposited": { "date-parts": [ [ 2023, 11, 19 ] ], "date-time": "2023-11-19T13:37:58Z", "timestamp": 1700401078000 }, "indexed": { "date-parts": [ [ 2023, 11, 20 ] ], "date-time": "2023-11-20T00:14:00Z", "timestamp": 1700439240890 }, "is-referenced-by-count": 0, "issue": "1", "issued": { "date-parts": [ [ 2023, 8, 29 ] ] }, "journal-issue": { "issue": "1", "published-online": { "date-parts": [ [ 2023, 12 ] ] } }, "language": "en", "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0", "content-version": "tdm", "delay-in-days": 0, "start": { "date-parts": [ [ 2023, 8, 29 ] ], "date-time": "2023-08-29T00:00:00Z", "timestamp": 1693267200000 } }, { "URL": "https://creativecommons.org/licenses/by/4.0", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2023, 8, 29 ] ], "date-time": "2023-08-29T00:00:00Z", "timestamp": 1693267200000 } } ], "link": [ { "URL": "https://link.springer.com/content/pdf/10.1186/s13054-023-04616-1.pdf", "content-type": "application/pdf", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://link.springer.com/article/10.1186/s13054-023-04616-1/fulltext.html", "content-type": "text/html", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://link.springer.com/content/pdf/10.1186/s13054-023-04616-1.pdf", "content-type": "application/pdf", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "297", "original-title": [], "prefix": "10.1186", "published": { "date-parts": [ [ 2023, 8, 29 ] ] }, "published-online": { "date-parts": [ [ 2023, 8, 29 ] ] }, "publisher": "Springer Science and Business Media LLC", "reference": [ { "DOI": "10.1146/annurev-pathol-011110-130158", "author": "MA Matthay", "doi-asserted-by": "publisher", "first-page": "147", "journal-title": "Annu Rev Pathol", "key": "4616_CR1", "unstructured": "Matthay MA, Zemans RL. 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