Abstract
Introduction: Coronavirus disease 2019 (COVID-19) causes a hypercoagulable state. Several autopsy studies have found microthrombi in pulmonary circulation.
Methods: In this randomized, open-label, phase II study, we randomized COVID-19 patients requiring mechanical ventilation to receive either therapeutic enoxaparin or the standard anticoagulant thromboprophylaxis. We evaluated the gas exchange over time through the ratio of partial pressure of arterial oxygen (PaO2) to the fraction of inspired oxygen (FiO2) at baseline, 7, and 14 days after randomization, the time until successful liberation from mechanical ventilation, and the ventilator-free days.
Results: Ten patients were assigned to the therapeutic enoxaparin and ten patients to prophylactic anticoagulation. There was a statistically significant increase in the PaO2/FiO2 ratio over time in the therapeutic group (163 [95% confidence interval – CI 133-193] at baseline, 209 [95% CI 171-247] after 7 days, and 261 [95% CI 230-293] after 14 days), p = 0.0004. In contrast, we did not observe this improvement over time in the prophylactic group (184 [95% CI 146-222] at baseline, 168 [95% CI 142-195] after 7 days, and 195 [95% CI 128-262] after 14 days), p = 0.487. Patients of the therapeutic group had a higher ratio of successful liberation from mechanical ventilation (hazard ratio: 4.0 [95% CI 1.035-15.053]), p = 0.031 and more ventilator-free days (15 days [interquartile range IQR 6-16] versus 0 days [IQR 0-11]), p = 0.028 when compared to the prophylactic group.
Conclusion: Therapeutic enoxaparin improves gas exchange and decreases the need for mechanical ventilation in severe COVID-19.
Trial registration: REBEC RBR-949z6v.
Keywords: Anticoagulant treatment; COVID-19; Coagulopathy; D-dimer; Mechanical ventilation.
【저자키워드】 COVID-19, Coronavirus disease 2019, acute respiratory distress syndrome, intensive care unit, D-dimer, Coagulopathy, Mechanical ventilation., body mass index, Disseminated intravascular coagulation, reverse transcriptase-polymerase chain reaction, creatinine clearance, Positive end-expiratory pressure, COVID-19coronavirus disease 2019, ICUIntensive Care Unit, ARDSacute respiratory distress syndrome, low molecular weight heparin, Anticoagulant treatment, aPTTactivated partial thromboplastin time, activated partial thromboplastin time, BMIbody mass index, CIconfidence interval, confidence interval, CrClcreatinine clearance, CKD-EPIChronic Kidney Disease Epidemiology Collaboration, Chronic Kidney Disease Epidemiology Collaboration, DICdisseminated intravascular coagulation, FiO2fraction of inspired oxygen, fraction of inspired oxygen, IQRinterquartile range, interquartile range, LMWHlow molecular weight heparin, PaO2partial pressure of arterial oxygen, partial pressure of arterial oxygen, PEEPpositive end-expiratory pressure, RT-PCRreverse transcriptase-polymerase chain reaction, SAPS3simplified acute physiology score 3, simplified acute physiology score 3, SICsepsis-induced coagulopathy score, sepsis-induced coagulopathy score, SOFAsequential organ failure assessment score, sequential organ failure assessment score, UFHunfractionated heparin, unfractionated heparin, ULNupper limit of normal, upper limit of normal, 【초록키워드】 anticoagulation, Open-label, randomization, severe COVID-19, mechanical ventilation, Ventilation, oxygen, Prophylactic, Randomized, Gas exchange, therapeutic, Patient, Ventilator-free days, circulation, Thromboprophylaxis, Anticoagulant, COVID-19 patient, microthrombi, hypercoagulable, FiO2, PaO2, PaO2/FiO2 ratio, fraction, decrease, observé, IMPROVE, evaluated, increase in, cause, assigned, autopsy study, statistically significant, receive, baseline, IQR, Mechanical, ventilator-free day, 【제목키워드】 clinical trial, anticoagulation, Prophylactic, Randomized,