Endothelial Protection in Convalescent COVID-19 Patients

Study Overview
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Brief Summary
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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.

Official Title
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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.

Conditions
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Endothelial Dysfunction, Inflammation, Thrombosis, COVID-19

Intervention / Treatment
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* Drug: Sulodexide


Participation Criteria
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Eligibility Criteria
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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 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 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sulodexide<br>Standard treatment plus oral sulodexide | Drug: Sulodexide<br>* Sulodexide 250 LSU 1 oral capsule twice daily for 8 weeks<br>|
| No Intervention: Control<br>Standard treatment only | |

What is the study measuring?
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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 |