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

Abstract

Background Sulodexide has pleiotropic properties within the vascular endothelium that can prove beneficial for the treatment of patients with COVID-19. We aimed to evaluate the effect of sulodexide when used in the early clinical stages of COVID-19. Methods In an outpatient setting, we conducted a randomized controlled trial with a parallel-group design. Including patients within three days of clinical onset, who were at a high risk of severe clinical progression due to chronic comorbidities. Participants were randomly assigned to receive an oral dose of sulodexide (500 LRU twice a day) or placebo for 21 days. Primary outcomes were need-length of hospitalization and need-length of oxygen support. Results Between June 5 and August 30, 2020, 243 patients were included in the per-protocol analysis. 124 of them received sulodexide, while 119 received placeboes. At 21 days follow-up, 17.7% patients required hospitalization in the sulodexide group compared to 29.4% in the placebo group, p=0.03. 29.8% required oxygen support in the sulodexide group vs 42% in the placebo group, p=0.05 and for fewer days [9 (7.2 SD) in the sulodexide group vs. 11.5 (9.6 SD) in the placebo group; p=0.02]. There was no between-group difference concerning the length of hospital stay. Interpretation Early intervention in COVID-19 patients with sulodexide reduced hospital admissions and oxygen support requirements. This has beneficial implications in the patient's well-being, making sulodexide a favorable medication until an effective vaccine or an antiviral becomes available. Funding Researcher independently initiated, partially funded by Alfasigma, Mexico. ISRCTN registry listed under ID ISRCTN59048638.

Interventions in an Ambulatory Setting to Prevent Progression to Severe Disease in Patients With COVID-19: A Systematic Review

“…Eight RCTs were identified relating to 9 pharmacological interventions (Table 2). [10][11][12][13][14][15][16][17] No trials were identified relating to nonpharmacological interventions.…”

“…All study participants were adults or adolescents (≥16 years old), were nonhospitalized, and had RT-PCR confirmed SARS-CoV-2 infection. Six of the 8 trials were placebo controlled, [10][11][12][13][14][15] and 2 were compared with usual care. 16,17 Trials were conducted in both developed and developing countries.…”

“…One study on oral sulodexide, conducted in Mexico, met our inclusion criteria. 11 Sulodexide is a highly purified mixture of glycosaminoglycans composed of low-molecular-weight heparin (80%), a blood thinner, and dermatan sulfate (20%). The study is a completed clinical trial, published as a preprint.…”

“…Only 3 of the 9 studies were considered at low risk of bias. 10,12,15 The main methodological concerns included the lack of placebo in the control group in 2 studies, 16,17 insufficient or absent blinding of outcome assessors and researchers, 11,16,17 and inadequate randomization procedures. 16,17 Half of the included trials are currently published only as preprints (4/8).…”

Viral-Induced Inflammatory Coagulation Disorders: Preparing for Another Epidemic

“…In addition to unfractionated and low-molecular-weight heparins, the effects of sulodexide, a highly purified mixture of glycosaminoglycans composed of low molecular weight heparin (80%) and dermatan sulfate (20%), is expected. The prevention of recurrent thromboembolism had already been shown in an RCT [112], and recent RCT revealed the prevention of disease progression in COVID-19 patients required hospitalization compared to the placebo group (relative risk [RR]: 0.6; 95% CI: 0.37-0.96) [113].…”