Use of defibrotide in COVID-19 pneumonia: comparison of a phase II study and a matched real-world cohort control

DOI record: { "DOI": "10.3324/haematol.2024.285345", "ISSN": [ "1592-8721", "0390-6078" ], "URL": "http://dx.doi.org/10.3324/haematol.2024.285345", "abstract": "<jats:p>The coronavirus disease 2019 (COVID-19) pandemic led to an unprecedented burden on healthcare systems around the world and a severe global socioeconomic crisis, with more than 750 million confirmed cases and at least 7 million deaths reported by December 31, 2023. The DEFI-VID19 study (clinicaltrials gov. Identifier: NCT04335201), a phase II, single-arm, multicenter, open-label trial was designed in mid-2020 to assess the safety and efficacy of defibrotide in treating patients with COVID-19 pneumonia. Defibrotide was administered at a dose of 25 mg/kg intravenously, divided into four daily doses over a planned 14-day period for patients with COVID-19 pneumonia receiving non-invasive ventilation. The primary endpoint was respiratory failure-free survival (RFFS). Overall survival (OS), the number of post-recovery days, and adverse events were the secondary endpoints. For comparison, a contemporaneous control cohort receiving standard of care only was retrospectively selected by applying the eligibility criteria of the DEFI-VID19 trial. To adjust for the imbalance between the two cohorts in terms of baseline variable distributions, an outcome regression analysis was conducted. In adjusted analysis, patients receiving defibrotide reported a trend towards higher RFFS (hazard ratio [HR]=0.71; 95% confidence interval [CI]: 0.34-1.29; P=0.138) and OS (HR=0.78; 95% CI: 0.33-1.53; P=0.248]) and showed a significantly increased number of post-recovery days (difference in means =3.61; 95% CI: 0.97-6.26; P=0.0037). Despite concomitant thromboprophylaxis with low molecular weight heparin, the safety profile of defibrotide proved to be favorable. Taken together, our findings suggest that defibrotide may represent a valuable addition to the COVID-19 therapeutic options.</jats:p>", "author": [ { "affiliation": [], "family": "Ruggeri", "given": "Annalisa", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "first" }, { "affiliation": [], "family": "Corrado", "given": "Francesco", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "additional" }, { "affiliation": [], "family": "Voza", "given": "Antonio", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "additional" }, { "affiliation": [], "family": "Wei", "given": "Lee-Jen", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "additional" }, { "affiliation": [], "family": "Catalano", "given": "Gloria", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "additional" }, { "affiliation": [], "family": "Liberatore", "given": "Carmine", "role": [ { "role": "author", "vocabulary": 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