Elsevier

Thrombosis Research

Volume 196, December 2020, Pages 359-366
Thrombosis Research

Full Length Article
Therapeutic versus prophylactic anticoagulation for severe COVID-19: A randomized phase II clinical trial (HESACOVID)

https://doi.org/10.1016/j.thromres.2020.09.026Get rights and content

Highlights

  • COVID-19 is associated with microthrombi in pulmonary circulation.

  • We randomized severe COVID-19 patients to receive either therapeutic enoxaparin or the standard thromboprophylaxis.

  • Therapeutic enoxaparin resulted in improved gas exchange over time.

  • Larger clinical trial is urgently needed to evaluate the anticoagulant therapy in severe COVID-19.

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.

Abbreviations

aPTT
activated partial thromboplastin time
ARDS
acute respiratory distress syndrome
BMI
body mass index
CI
confidence interval
CrCl
creatinine clearance
COVID-19
Coronavirus disease 2019
CKD-EPI
Chronic Kidney Disease Epidemiology Collaboration
DIC
disseminated intravascular coagulation
FiO2
fraction of inspired oxygen
ICU
intensive care unit
IQR
interquartile range
LMWH
low molecular weight heparin
PaO2
partial pressure of arterial oxygen
PEEP
positive end-expiratory pressure
RT-PCR
reverse transcriptase-polymerase chain reaction
SAPS3
simplified acute physiology score 3
SIC
sepsis-induced coagulopathy score
SOFA
sequential organ failure assessment score
UFH
unfractionated heparin
ULN
upper limit of normal

Keywords

COVID-19
Mechanical ventilation
Anticoagulant treatment
D-dimer
Coagulopathy

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