Defibrotide Therapy for SARS-CoV-2 ARDS

被引:0
|
作者
Frame, David [1 ,2 ]
Scappaticci, Gianni B. [1 ,2 ]
Braun, Thomas M. [7 ]
Maliarik, Mary [3 ]
Sisson, Thomas H. [3 ]
Pipe, Steven W. [6 ]
Lawrence, Daniel A. [5 ]
Richardson, Paul G. [9 ]
Holinstat, Michael [8 ]
Hyzy, Robert C. [3 ]
Kaul, Daniel R.
Gregg, Kevin S.
Lama, Vibha N. [3 ,4 ]
Yanik, Gregory A. [1 ,6 ]
机构
[1] Univ Michigan, Med Sch, Blood & Marrow Transplant Program, Ann Arbor, MI 48103 USA
[2] Univ Michigan, Med Sch, Dept Clin Pharm, Ann Arbor, MI USA
[3] Univ Michigan, Med Sch, Div Pulm & Crit Care Med, Ann Arbor, MI USA
[4] Univ Michigan, Med Sch, Dept Cardiovasc Med, Ann Arbor, MI 48103 USA
[5] Univ Michigan, Med Sch, Div Infect Dis, Ann Arbor, MI 48103 USA
[6] Univ Michigan, Med Sch, Dept Internal Med, Div Pediat Hematol Oncol, Ann Arbor, MI 48103 USA
[7] Univ Michigan, Med Sch, Dept Biostat, Dept Pediat,Michigan Med, Ann Arbor, MI USA
[8] Univ Michigan, Div Pharmacol, Sch Publ Hlth, Ann Arbor, MI USA
[9] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Div Hematol Malignancies, Boston, MA USA
关键词
KEY WORDS; ARDS; COVID-19; de fi brotide; SARS-CoV-2; SEVERE VENOOCCLUSIVE DISEASE; COVID-19; COAGULOPATHY; OUTCOMES; ADULTS; BLOOD;
D O I
暂无
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
BACKGROUND: SARS-CoV-2-related ARDS is associated with endothelial dysfunction and profound dysregulation of the thrombotic-fibrinolytic pathway. Defibrotide is a polyanionic compound with fibrinolytic, antithrombotic, and antiinflammatory properties. RESEARCH QUESTION: What is the safety and tolerability of defibrotide in patients with severe SARS-CoV-2 infections? STUDY DESIGN AND METHODS: We report a prospective, open-label, single-center safety trial of defibrotide for the management of SARS-CoV-2-related ARDS. Eligible participants were 18 years of age or older with clinical and radiographic signs of ARDS, no signs of active bleeding, a serum D-dimer of more than twice upper limit of normal, and positive polymerase chain reaction-based results for SARS-CoV-2. Defibrotide (6.25 mg/kg/dose IV q6h) was administered for a planned 7-day course, with serum D-dimer levels and respiratory function monitored daily during therapy. RESULTS: Twelve patients (median age, 63 years) were treated, with 10 patients receiving mechanical ventilation and 6 receiving vasopressor support at study entry. The median D-dimer was 3.25 mg/ml (range, 1.33-12.3) at study entry. The median duration of therapy was 7 days. No hemorrhagic or thrombotic complications occurred during therapy. No other adverse events attributable to defibrotide were noted. Four patients met the day 7 pulmonary response parameter, all four showing a decrease in serum D-dimer levels within the initial 72 h of defibrotide therapy. Three patients died of progressive pulmonary disease 11, 17, and 34 days after study entry. Nine patients (75%) remain alive 64 to 174 days after initiation of defibrotide. Day 30 all-cause mortality was 17% (95% CI, 0%-35%). All patients with a baseline PaO2 to FIO2 ratio of $ 125 mm Hg survived, whereas the three patients with a baseline PaO2 to FIO2 ratio of < 125 mm Hg died. INTERPRETATION: The use of defibrotide for management of SARS-CoV-2-related ARDS proved safe and tolerable. No hemorrhagic or thrombotic complications were reported during therapy, with promising outcomes in a patient population with a historically high mortality rate.
引用
收藏
页码:346 / 355
页数:10
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