tetano
Editor, Senior Moderator
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[SUP] 1 [/SUP], Francesco Corrado[SUP] 2 [/SUP], Antonio Voza[SUP] 3 [/SUP], Lee-Jen Wei[SUP] 4 [/SUP], Gloria Catalano[SUP] 1 [/SUP], Carmine Liberatore[SUP] 1 [/SUP], Rosamaria Nitti[SUP] 1 [/SUP], Carlo Fedeli[SUP] 5 [/SUP], Alessandro Bruno[SUP] 1 [/SUP], Eleonora Calabretta[SUP] 2 [/SUP], Fabio Giglio[SUP] 1 [/SUP], Fabio Sciutti[SUP] 6 [/SUP], Francesca Lunghi[SUP] 1 [/SUP], Giovanni Landoni[SUP] 7 [/SUP], Alessio Aghemo[SUP] 8 [/SUP], Massimo Iacobelli[SUP] 9 [/SUP], Patrizia Rovere Querini[SUP] 10 [/SUP], Paul G Richardson[SUP] 11 [/SUP], Andrea Assanelli[SUP] 1 [/SUP], Jacopo Peccatori[SUP] 1 [/SUP], Fabio Ciceri[SUP] 12 [/SUP], Carmelo Carlo-Stella[SUP] 13 [/SUP]
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[SUP] 1 [/SUP], Francesco Corrado[SUP] 2 [/SUP], Antonio Voza[SUP] 3 [/SUP], Lee-Jen Wei[SUP] 4 [/SUP], Gloria Catalano[SUP] 1 [/SUP], Carmine Liberatore[SUP] 1 [/SUP], Rosamaria Nitti[SUP] 1 [/SUP], Carlo Fedeli[SUP] 5 [/SUP], Alessandro Bruno[SUP] 1 [/SUP], Eleonora Calabretta[SUP] 2 [/SUP], Fabio Giglio[SUP] 1 [/SUP], Fabio Sciutti[SUP] 6 [/SUP], Francesca Lunghi[SUP] 1 [/SUP], Giovanni Landoni[SUP] 7 [/SUP], Alessio Aghemo[SUP] 8 [/SUP], Massimo Iacobelli[SUP] 9 [/SUP], Patrizia Rovere Querini[SUP] 10 [/SUP], Paul G Richardson[SUP] 11 [/SUP], Andrea Assanelli[SUP] 1 [/SUP], Jacopo Peccatori[SUP] 1 [/SUP], Fabio Ciceri[SUP] 12 [/SUP], Carmelo Carlo-Stella[SUP] 13 [/SUP]
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.