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Haematologica
. 2024 May 23.
doi: 10.3324/haematol.2024.285345. Online ahead of print. Use of defibrotide in COVID-19 pneumonia: comparison of a phase II study and a matched real-world cohort control
Annalisa Ruggeri 1 , Francesco Corrado 2 , Antonio Voza 3 , Lee-Jen Wei 4 , Gloria Catalano 1 , Carmine Liberatore 1 , Rosamaria Nitti 1 , Carlo Fedeli 5 , Alessandro Bruno 1 , Eleonora Calabretta 2 , Fabio Giglio 1 , Fabio Sciutti 6 , Francesca Lunghi 1 , Giovanni Landoni 7 , Alessio Aghemo 8 , Massimo Iacobelli 9 , Patrizia Rovere Querini 10 , Paul G Richardson 11 , Andrea Assanelli 1 , Jacopo Peccatori 1 , Fabio Ciceri 12 , Carmelo Carlo-Stella 13
Affiliations
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 31st December 2023. The DEFI-VID19 study (ClinicalTrials.gov 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/d 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 (HR=0.71[0.95CI: 0.34 to 1.29, P= .138]) and OS (HR=0.78[0.95CI: 0.33 to 1.53, P= .248]) and showed a significantly increased number of post-recovery days (difference in means: 3.61[ 0.95CI: 0.97 to 6.26, P= .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.
. 2024 May 23.
doi: 10.3324/haematol.2024.285345. Online ahead of print. Use of defibrotide in COVID-19 pneumonia: comparison of a phase II study and a matched real-world cohort control
Annalisa Ruggeri 1 , Francesco Corrado 2 , Antonio Voza 3 , Lee-Jen Wei 4 , Gloria Catalano 1 , Carmine Liberatore 1 , Rosamaria Nitti 1 , Carlo Fedeli 5 , Alessandro Bruno 1 , Eleonora Calabretta 2 , Fabio Giglio 1 , Fabio Sciutti 6 , Francesca Lunghi 1 , Giovanni Landoni 7 , Alessio Aghemo 8 , Massimo Iacobelli 9 , Patrizia Rovere Querini 10 , Paul G Richardson 11 , Andrea Assanelli 1 , Jacopo Peccatori 1 , Fabio Ciceri 12 , Carmelo Carlo-Stella 13
Affiliations
- PMID: 38779740
- DOI: 10.3324/haematol.2024.285345
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 31st December 2023. The DEFI-VID19 study (ClinicalTrials.gov 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/d 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 (HR=0.71[0.95CI: 0.34 to 1.29, P= .138]) and OS (HR=0.78[0.95CI: 0.33 to 1.53, P= .248]) and showed a significantly increased number of post-recovery days (difference in means: 3.61[ 0.95CI: 0.97 to 6.26, P= .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.