Endothelial Protection in Convalescent COVID-19 Patients
Study Details
Study Description
Brief Summary
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 4 |
Study Design
Arms and Interventions
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 |
Outcome Measures
Primary Outcome Measures
- Serum level of soluble Thrombomodulin [8 weeks]
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.
Secondary Outcome Measures
- Serum level of Von Willebrand factor [8 weeks]
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.
- Serum level of ICAM-1 [8 weeks]
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.
- Serum level of VCAM-1 [8 weeks]
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.
- Serum level of soluble P-selectin [8 weeks]
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.
- Serum level of circulating endothelial cells [8 weeks]
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
- Serum level of high sensitive C reactive protein [8 weeks]
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.
- Serum level of Interleukine-6 [8 weeks]
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.
Other Outcome Measures
- Serum level of D-dimer [8 weeks]
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.
- Serum level of fibrinogen [8 weeks]
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.
- Platelets count in peripheral blood [8 weeks]
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.
- Post-COVID-19 functional status [8 weeks]
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).
- Clinical progression of COVID-19 [8 weeks]
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).
- Thrombotic complications [8 weeks]
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).
- Major bleeding as defined by International Society on Thrombosis and Haemostasis (ISTH) criteria [8 weeks]
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.
- Clinically relevant non-major bleedingas defined by International Society on Thrombosis and Haemostasis (ISTH) criteria [8 weeks]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
over 18 years old
-
male or female
-
documented PCR SARS-CoV-2 positive test
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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)
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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
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less than 14 days of hospital discharge.
Exclusion Criteria:
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concomitant use of another anticoagulant
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known pregnancy
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known hypersensitivity to sulodexide
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need for hospital care at screening
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renal insufficiency with CrCl <30ml/min or continuous renal replacement therapy, hemodialysis, or peritoneal dialysis.
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blood platelet count < 30 000/µL
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other conditions that are judged to carry an increased risk of bleeding as judged by the Investigator
-
more than 30 days of clinical onset
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Moscow Clinical Hospital no.24 | Moscow | Russian Federation | 127015 |
Sponsors and Collaborators
- Pirogov Russian National Research Medical University
Investigators
- Principal Investigator: Kirill Lobastov, PhD, Pirogov Russian National Research Medical University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SDXbioCOVID-19