Alteplase in COVID-19 severe hypoxemic respiratory failure: the TRISTARDS multicenter randomized trial

被引:0
作者
Landoni, Giovanni [1 ,2 ]
Chowdary, Pratima [3 ]
Meziani, Ferhat [4 ]
Creteur, Jacques [5 ]
De Schryver, Nicolas [6 ]
Motsch, Johann [7 ]
Henrichmoeller, Ingrid [8 ,9 ]
Pages, Alain [8 ]
Peter, Nuala [10 ]
Danays, Thierry [11 ]
Weigand, Markus A. [7 ]
机构
[1] IRCCS San Raffaele Sci Inst, Dept Anesthesia & Intens Care, Milan, Italy
[2] Univ Vita Salute San Raffaele, Sch Med, Milan, Italy
[3] Royal Free Hosp, Katharine Dormandy Haemophilia & Thrombosis Ctr, London, England
[4] Univ Strasbourg UNISTRA, Hop Univ Strasbourg, Nouvel Hop Civil, Fac Med,Serv Med Intens Reanimat, Strasbourg, France
[5] ULB, Hop Erasme, Dept Intens Care, Brussels, Belgium
[6] Clin St Pierre, Intens Care Unit, Ottignies, Belgium
[7] Heidelberg Univ Hosp, Dept Anesthesiol, Heidelberg, Germany
[8] Boehringer Ingelheim Int GmbH, Therapeut Area Cardiovasc Med, Ingelheim, Germany
[9] Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Mannheim, Germany
[10] Boehringer Ingelheim GmbH & Co KG, Biberach, Germany
[11] TDC, Aix En Provence, France
来源
ANNALS OF INTENSIVE CARE | 2024年 / 14卷 / 01期
关键词
Alteplase; ARDS; COVID-19; Severe hypoxemic respiratory failure; Thrombolysis; DISTRESS-SYNDROME; GUIDELINES; CARE;
D O I
10.1186/s13613-024-01386-z
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Background Pulmonary intravascular thrombus formation has been widely observed in patients with respiratory failure, for example, in patients with SARS-CoV-2 infection (COVID-19). The aim of this study was to evaluate the efficacy/safety of alteplase thrombolysis in COVID-19 severe hypoxemic respiratory failure. In this multicenter, open-label study, patients were randomized to receive alteplase (low- or high-dose) over 5 days plus standard of care (SOC), or SOC alone. The primary endpoint was time to clinical improvement (>= 2-point decrease on WHO Clinical Progression Scale, or hospital discharge) up to Day 28. Secondary endpoints included all-cause mortality at Day 28, treatment failure at Day 28 and change in arterial oxygen partial pressure/fractional inspired oxygen (PaO2/FiO(2)) ratio at Day 6 versus baseline. Results Sixty-nine patients were randomized to alteplase (low- or high-dose) and 35 to SOC; 65% were on high-flow oxygen or non-invasive ventilation at baseline. Median time to clinical improvement was 25 days in the alteplase group and > 28 days (median not reached) in the SOC group. All-cause mortality was 8/69 (12%) versus 10/35 (29%) in the alteplase versus SOC groups, respectively (unadjusted risk difference [RD], - 17% [95% confidence interval (CI) - 34 to 0], p = 0.047; adjusted RD, - 16% [95% CI - 31 to 1], p = 0.058). The PaO2/FiO(2) ratio (mean [standard deviation]) increased by + 30 (84) mmHg in the alteplase group and decreased by - 12 (59) mmHg in the SOC group (adjusted mean difference vs. SOC, p = 0.052). Differences were greater in patients receiving high-dose alteplase, and in those not receiving invasive ventilation. Eighteen patients (26.1%) in the alteplase group discontinued treatment due to adverse events. Major bleeding was more frequent with alteplase than with SOC (9 vs. 0 patients); no bleeding was fatal. The study closed early due to insufficient patient recruitment. Conclusion Alteplase was not associated with faster clinical recovery from COVID-19 severe hypoxemic respiratory failure. A numerical difference in survival and PaO2/FiO(2) ratio was observed, particularly in patients not receiving invasive ventilation. These exploratory findings merit further investigation in larger patient cohorts that are adequately powered to confirm the hypotheses generated in this study regarding the impact of alteplase on treatment outcomes. Trial registration ClinicalTrials.gov: NCT04640194 (November 23, 2020); https://clinicaltrials.gov/study/NCT04640194 (early discontinuation due to insufficient patient recruitment).
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