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

Background: Targeting endothelial cells has been suggested for the treatment of patients with COVID-19 and sulodexide has pleiotropic properties within the vascular endothelium that can prove beneficial to the same. We aimed to evaluate the effect of sulodexide when used in the early clinical stages of COVID-19.  Methods: We conducted a single-centre, outpatient setting, randomized controlled trial with a parallel-group design in Mexico. Including patients within three days of clinical symptom onset, who were at a high risk of severe clinical progression due to chronic comorbidities. Participants were randomly allocated to receive an oral dose of sulodexide (500 LRU twice a day) or the placebo for 21 days. Primary outcomes were need and length of hospitalisation, need and length of oxygen support and mortality.  Results: Between June 5 and August 30, 2020, 243 patients were included in the “per-protocol” analysis. One hundred twenty-four of them received sulodexide, while 119 received placeboes. At 21 days follow-up, 22 of 124 patients required hospitalisation in the sulodexide group compared to 35 of 119 in the placebo group [relative risk (RR), 0·6; 95% confidence interval (CI), 0·37-0·96; p=0·03]. Fewer patients required oxygen support in the sulodexide group [37 of 124 vs. 50 of 119; RR, 0·71; 95% CI, 0·5 to 1; p=0·05], and for fewer days (9±7·2 in the sulodexide group vs. 11·5±9·6 in the placebo group; p=0·02). There was no between-group difference concerning the length of hospital stay or mortality.  Interpretation: Early intervention in COVID-19 patients with sulodexide reduced hospital admissions and oxygen support requirements, although with no significant effect on mortality. This has beneficial implications in the patient well-being, making sulodexide a favourable medication until an effective vaccine or an antiviral becomes available.  Trial Registration: Listed in the ISRCTN registry under ID ISRCTN59048638. Funding: Researcher independently initiated, partially funded by Alfasigma, Mexico.  Declaration of Interests: AGO has received speaker fees, honoraria and travel reimbursement from Alfasigma Mexico for research outside of this submitted study. All other authors declare no competing interests. Ethics Approval Statement: We conducted this trial according to the Declaration of Helsinki and it was board reviewed by the Universidad Autonoma de Baja California Faculty of Medicine Mexicali Ethics and Investigation Committee, being designated with approval number FMM/CEI/0011/2020-2.