A randomized, placebo-controlled study led by researchers from Mexico involving 243 patients led to the conclusion of investigators that supports the effectiveness of the the use of the two-compound drug sulodexide in the prevention of severe clinical progression of COVID-19 when used during the early symptomatic stage as compared to the standard of care. The investigators here declare that at least for purposes of this controlled study that the use of the study drug reduced the need for hospital care of these patients diagnosed with COVID-19. The results of this study were recently published in the Journal of Vascular Surgery: Venous and Lymphatic Disorders.
The study team sought to investigate this drug as early investigations show an increased risk of thromboembolic complications as well as a systemic inflammatory response, though neither is clearly understood.
Note that the U.S. National Institutes of Health (NIH) ACTIV-4 program also investigates antithrombotic and, in one study, the study team found that full dose anticoagulation treatments, such as affordable heparin, given to moderately ill patients hospitalized for COVID-19, reduced the requirement of vital organ support, such as the need for mechanical ventilation.
Sulodexide is a highly purified mixture of glycosaminoglycans composed of low molecular weight heparin (80%) and dermatan sulfate (20%) as recorded in Wikipedia. Known under the trade name Aterina, this two-compound drug, each with a different endothelial action inclusive of potential benefit to the COVID-19 patient was employed by the study team du to: A) glycosaminoglycans can potentially restore venous and arterial endothelial glycocalyx—involved with downregulation or limitation of response to inflammatory molecules, and B) heparin compound has antithrombotic effects that can reduce the incidence of thromboembolic complications while also introducing potential anti-inflammatory responses. The medication can be administered orally with minimal adverse effects while less in cost than low molecular weight heparin.
The study team sought to test the hypothesis that the study drug called sulodexide administered early in populations facing greater risk as well as symptomatic patient affected with COVID-19 (e.g. range of common symptoms) as well as other risk factors (e.g. comorbidities such as hypertension, diabetes, etc.) will provide improvement in endothelial integrity, reductio in inflammatory responses and improved clinical outcomes including reduced hospital admission, less VTE and arterial complications, morbidity and mortality.
Hence, in this study (NCT04483830), the use of the study drug in patients with early onset of COVID-19 symptoms to mitigate the progression of the disease process, supporting recovery at home while limiting the need of hospital care, was put to the test.
After randomly assigning the 243 patients to the sulodexide group (n=124) or the placebo (n=119) the team also ensured that the demographics matched well among the different groups, although the results don’t give too many details.
The study team reported a statistical significant improvement in the number of clinical symptoms of body aches at week 2 (P = .002), malaise/fatigue at week 3 (P = .003), and shortness of breath at week 2 (P = .001) andweek3 (P = .031). A total of 37 patients (29%) developed respiratory symptoms that warrant the need for in-home oxygen support in the sulodexide group versus 50 (42%) in the control group (P = .047). A total of 56 patients (24%) required hospital admission, 22 (17.7%) in the sulodexide group and 35 (29.4%) in the placebo group (P = .032), with an average length of stay of 6.4 days in the sulodexide group versus 7.8 control group (P = .211). A total of 3 patients (2.4%) died in the sulodexide group versus 7 (5.8%) in the placebo group (P = .121).
The study was sponsored by Clinedem, a health center for both medical and dental services in San Luis, Mexico. One of the study authors works with the Instituto Mexicano Seguro Social, actually the Mexican Institute of Social Security, a government organization that assists public health pensions and social security in Mexico operating under the Secretariat of Health. This institution forms an integral part of the Mexican healthcare system. Also a collaborator in this study was Italy-headquartered Alfasigma S.p.A.
· Alejandro Gonzalez-Ochoa, Instituto Mexicano Seguro Social HGZ#12, San Luis, RC, Mexico; Clinedem
· Ana Hernandez, Clinedem, San Luis, RC, Mexico
· Joseph Raffetto, Boston University, School of Medicine, Boston, MA