Sulodexide in the Treatment of Patients with Early Stages of COVID-19: A Randomized Controlled Trial

Thromb Haemost. 2021 Jul;121(7):944-954. doi: 10.1055/a-1414-5216. Epub 2021 Mar 7.


Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may induce several vascular endothelial-dependent systemic complications, and sulodexide has pleiotropic actions on the vascular endothelium, which may prove beneficial. We aimed to assess the effect of sulodexide when used within 3 days of coronavirus disease 2019 (COVID-19) clinical onset. We conducted a randomized placebo-controlled outpatient trial. To be included, patients must have been at high risk for severe clinical progression. Participants received sulodexide (oral 1,000 LRU/d) or placebo for 21 days. The primary endpoint was the need for hospital care. Also assessed were patients' need for supplemental oxygen as well as D-dimer and C-reactive protein (CRP) levels, thromboembolic events, major bleeding, and mortality. A total of 243 patients were included in the per-protocol analysis from June 5 to August 30, 2020. Of these, 124 received sulodexide and 119 received a placebo. Only 17.7% of the patients in the sulodexide group required hospitalization, compared with 29.4% in the placebo group (p = 0.03). This benefit persisted in the intention-to-treat analysis (15% in sulodexide group vs. 24% with placebo [p = 0.04]). With sulodexide, fewer patients required supplemental oxygen (30 vs. 42% [p = 0.05]). After 2 weeks, fewer patients had D-dimer levels >500 ng/dL (22 vs. 47% [p < 0.01]), and patients also had lower mean CRP levels (12.5 vs. 17.8 mg/dL [p < 0.01]). There were no between-group differences in thromboembolic events, major bleeding, or mortality. Treatment of COVID-19 patients with sulodexide, when provided within 3 days of clinical onset, improved their clinical outcomes. Although the results should be confirmed, sulodexide could be valuable in an outpatient setting.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Ambulatory Care
  • Biomarkers / blood
  • C-Reactive Protein / metabolism
  • COVID-19 / blood
  • COVID-19 / diagnosis
  • COVID-19 / drug therapy*
  • COVID-19 / mortality
  • Disease Progression
  • Female
  • Fibrin Fibrinogen Degradation Products / metabolism
  • Fibrinolytic Agents / adverse effects
  • Fibrinolytic Agents / therapeutic use*
  • Glycosaminoglycans / adverse effects
  • Glycosaminoglycans / therapeutic use*
  • Humans
  • Male
  • Mexico
  • Middle Aged
  • Oxygen Inhalation Therapy
  • Patient Admission
  • Prospective Studies
  • Time Factors
  • Treatment Outcome


  • Biomarkers
  • Fibrin Fibrinogen Degradation Products
  • Fibrinolytic Agents
  • Glycosaminoglycans
  • fibrin fragment D
  • glucuronyl glucosamine glycan sulfate
  • C-Reactive Protein

Supplementary concepts

  • COVID-19 drug treatment