Thromb Haemost 2021; 121(07): 944-954
DOI: 10.1055/a-1414-5216
New Technologies, Diagnostic Tools and Drugs

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

1  Department of Vascular-Endovascular Surgery, CLINEDEM, Colonia Comercial, San Luis Rio Colorado, Sonora, México
2  Division of Vascular Surgery, Department of Surgery, Hospital General de Zona No12 Instituto Mexicano Seguro Social, San Luis Rio Colorado, Sonora, México
,
Joseph D. Raffetto
3  Department of Surgery, Brigham and Women's Hospital, VA Boston Healthcare System, Harvard University, Boston, Massachusetts, United States
,
Ana G. Hernández
4  Department of Otorhinolaryngology, CLINEDEM, Colonia Comercial, San Luis Rio Colorado, Sonora, México
,
Nestor Zavala
5  Hospital General de Zona No12 Instituto Mexicano Seguro Social, San Luis Rio Colorado, Sonora, México
,
Obed Gutiérrez
6  Department of Emergency Medicine, Hospital General de Zona No12 Instituto Mexicano Seguro Social, San Luis Rio Colorado, Sonora, México
7  Department of Emergency, Hospital General, San Luis Rio Colorado, Sonora, México
,
Arturo Vargas
8  Urban Outpatient Care Center, Secretaria de Salud, San Luis Rio Colorado, Sonora, México
,
Jorge Loustaunau
9  Department of Emergency, Hospital General de Zona No12 Instituto Mexicano Seguro Social, San Luis Rio Colorado, Sonora, México
› Author Affiliations
Funding This study was independently initiated by the lead researcher and partially funded by Alfasigma Mexico, with the latter providing the sulodexide and placebo capsules for the duration of the trial. Alfasigma did not take part in enrolling trial participants; collecting, managing, analyzing, and interpreting the data; or the decision to submit the report for publication.

Abstract

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.

Note

The data analyzed and presented in this study are available from the corresponding author upon reasonable request, providing that the request meets local ethical and research governance criteria. This trial is listed in the ISRCTN registry with the study ID ISRCTN59048638.


Supplementary Material



Publication History

Received: 26 December 2020

Accepted: 05 March 2021

Publication Date:
07 March 2021 (online)

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