Endothelial Dysfunction, Inflammation, Thrombosis, COVID-19
Conditions
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.
Interventions
DRUGSulodexide
Sulodexide 250 LSU 1 oral capsule twice daily for 8 weeks
Sponsors
Pirogov Russian National Research Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Russia
Outcome results
None listed