Endothelial Protection in Convalescent COVID-19 Patients

Endothelial Protection in Convalescent COVID-19 Patients. The Effect of Sulodexide on Serum Levels of Biomarkers for Endothelial Dysfunction. A Pilot Prospective, Randomized, Open-label, Investigator-initiated Trial.

This pilot open-label randomized controlled trial aims to assess if treatment with sulodexide may improve the endothelial status and inflammatory response in post-COVID-19 patients. Survived inpatients with severe-to-critical COVID-19 within 14 days after discharge are randomized to receive sulodexide 250 LSU 1 oral capsule twice daily or no treatment for 8 weeks. Biomarkers of endothelial dysfunction, inflammation, and prothrombotic changes are assessed at 0, 4, and 8 weeks. The hypothesis is that affected endothelial function, pro-inflammatory, and pro-thrombotic changes could be improved with sulodexide treatment in convalescent COVID-19 patients who suffered a severe-to-critical clinical presentation and have chronic comorbidities of high risk for endothelial dysfunction.

Study Overview

• Status: Terminated
• Conditions: COVID-19; Inflammation; Thrombosis; Endothelial Dysfunction
• Intervention / Treatment: Drug: Sulodexide

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 4

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 127015
    • Moscow Clinical Hospital no.24

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• over 18 years old
• male or female
• documented PCR SARS-CoV-2 positive test
• COVID-19 convalescence (define as at least 10 days after the onset of symptoms, no fever for at least 24 hours without the use of antipyretics and improvement of respiratory symptoms)
• informed consent signed

• clinical severity presentation of

  1. Severe the disease is classified as severe if one of the following conditions is met:

     Respiratory distress, respiratory rate ≥30/min Oxygen saturation on room air at rest ≤93%. Partial pressure of oxygen in arterial blood/FiO2 ≤300 mm Hg. Or

  2. Critical if one of the following conditions is met. Respiratory failure and mechanical ventilation are required. Shock occurs Another organ dysfunction is present
• risk of health complication >50% according to the health risk calculator
• less than 14 days of hospital discharge.

Exclusion Criteria:

• concomitant use of another anticoagulant
• known pregnancy
• known hypersensitivity to sulodexide
• need for hospital care at screening
• renal insufficiency with CrCl <30ml/min or continuous renal replacement therapy, hemodialysis, or peritoneal dialysis.
• blood platelet count < 30 000/µL
• other conditions that are judged to carry an increased risk of bleeding as judged by the Investigator
• more than 30 days of clinical onset

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sulodexide; Standard treatment plus oral sulodexide	Drug: Sulodexide; Sulodexide 250 LSU 1 oral capsule twice daily for 8 weeks
No Intervention: Control; Standard treatment only

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum level of soluble Thrombomodulin	The level of serum soluble Thrombomodulin will be measured at 0, 4, and 8 weeks by ELISA test to detect endothelial dysfunction and its improvement.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum level of Von Willebrand factor	The level of serum Von Willebrand factor will be measured at 0, and 8 weeks by ELISA test to detect pro-thrombotic status, endothelial dysfunction, and their improvement.	8 weeks
Serum level of ICAM-1	The level of serum ICAM-1 will be measured at 0, and 8 weeks by ELISA test to detect pro-inflammatory status, endothelial dysfunction, and their improvement.	8 weeks
Serum level of VCAM-1	The level of serum VCAM-1 will be measured at 0, and 8 weeks by ELISA test to detect pro-inflammatory status, endothelial dysfunction, and their improvement.	8 weeks
Serum level of soluble P-selectin	The level of serum soluble P-selectin will be measured at 0, and 8 weeks by ELISA test to detect pro-inflammatory status, pro-thrombotic changes, endothelial dysfunction, and their improvement.	8 weeks
Serum level of circulating endothelial cells	The level of circulating endothelial cells will be measured at 0, and 8 weeks by standardized flow cytometry to detect endothelial dysfunction and its improvement	8 weeks
Serum level of high sensitive C reactive protein	The level of high sensitive C reactive protein will be measured at 0, and 8 weeks by ELISA test to detect pro-inflammatory status, endothelial dysfunction, and their improvement.	8 weeks
Serum level of Interleukine-6	The level of serum Interleukine-6 will be measured at 0, and 8 weeks by ELISA test to detect pro-inflammatory status, endothelial dysfunction, and their improvement.	8 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum level of D-dimer	The level of serum D-dimer will be measured at 0, 4, and 8 weeks by ELISA test to detect pro-inflammatory status, pro-thrombotic changes, endothelial dysfunction, and their improvement.	8 weeks
Serum level of fibrinogen	The level of serum fibrinogen will be measured at 0, 4, and 8 weeks by ELISA test to detect pro-inflammatory status, pro-thrombotic changes, endothelial dysfunction, and their improvement.	8 weeks
Platelets count in peripheral blood	Platelets count in peripheral blood will be measured at 0, 4, and 8 weeks by standard automatic analyzer for complete blood count to detect pro-inflammatory status, pro-thrombotic changes, endothelial dysfunction, and their improvement.	8 weeks
Post-COVID-19 functional status	Post-COVID-19 functional status will be assessed at 0, 4, and 8 weeks by a specific questionnaire "Post-COVID-19 Functional Status (PCFS)" scale that ranges from 0 (no limitations) to 4 (severe limitations).	8 weeks
Clinical progression of COVID-19	Clinical progression of COVID-19 will be assessed at 0, 4, and 8 weeks by a specific World Health Organization Clinical progression scale that ranges from 0 (no infection) to 10 (death due to infection).	8 weeks
Thrombotic complications	Venous (deep vein thrombosis, superficial vein thrombosis, pulmonary embolism) and arterial (myocardial infarction, stroke, acute limb ischemia) thrombosis will be assessed on a clinical basis and should be confirmed by appropriate imaging (duplex ultrasound scan, computed tomography scan with contrast, arterial and venous angiography).	8 weeks
Major bleeding as defined by International Society on Thrombosis and Haemostasis (ISTH) criteria	Major bleeding as defined by the International Society on Thrombosis and Haemostasis (fatal bleeding, and/or symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome, and/or bleeding causing a fall in hemoglobin level of 2 g/dL (1.24 mmol/L) or more, or leading to transfusion of two or more units of whole blood or red cells) will be assessed on a clinical basis and should be confirmed by appropriate laboratory and instrumental tests.	8 weeks
Clinically relevant non-major bleedingas defined by International Society on Thrombosis and Haemostasis (ISTH) criteria	Clinically relevant non-major bleeding as defined by the International Society on Thrombosis and Haemostasis (requiring medical intervention by a healthcare professional, and/or leading to hospitalization, and/or increased level of care prompting a face to face [i.e., not just a telephone or electronic communication] evaluation) will be assessed on a clinical basis and should be confirmed by appropriate laboratory and instrumental tests.	8 weeks

Collaborators and Investigators

• Sponsor: Pirogov Russian National Research Medical University
• Investigators: Principal Investigator: Kirill Lobastov, PhD, Pirogov Russian National Research Medical University

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2022
• Primary Completion (Actual): September 1, 2022
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: February 21, 2022
• First Submitted That Met QC Criteria: February 21, 2022
• First Posted (Actual): February 23, 2022

Study Record Updates

• Last Update Posted (Actual): June 13, 2025
• Last Update Submitted That Met QC Criteria: June 11, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19; Thrombosis; Inflammation; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Fibrin Modulating Agents; Antimetabolites; Fibrinolytic Agents; Anticoagulants; Hypolipidemic Agents; Lipid Regulating Agents; Glucuronyl glucosamine glycan sulfate
• Other Study ID Numbers: SDXbioCOVID-19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No