1. Use of defibrotide in COVID-19 pneumonia: comparison of a phase II study and a matched real-world cohort control.
- Author
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Ruggeri A, Corrado F, Voza A, Wei LJ, Catalano G, Liberatore C, Nitti R, Fedeli C, Bruno A, Calabretta E, Giglio F, Sciutti F, Lunghi F, Landoni G, Aghemo A, Iacobelli M, Querini PR, Richardson PG, Assanelli A, Peccatori J, Ciceri F, and Carlo-Stella C
- Subjects
- Humans, Male, Female, Middle Aged, Aged, Treatment Outcome, Adult, Aged, 80 and over, Cohort Studies, Retrospective Studies, COVID-19 Drug Treatment, COVID-19 mortality, COVID-19 complications, COVID-19 epidemiology, SARS-CoV-2, Polydeoxyribonucleotides therapeutic use
- Abstract
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.
- Published
- 2024
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