Endothelial Protection in Convalescent COVID-19 Patients

COVID-19 Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05252923
• Other study ID #: SDXbioCOVID-19
• Status: Recruiting
• Phase: Phase 4
• Start date: April 1, 2022
• Est. completion date: December 31, 2022

Study information

• Verified date: February 2022
• Source: Pirogov Russian National Research Medical University
• Contact: Kirill Lobastov, PhD
• Phone: +79852116331
• Email: lobastov_kv[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 31, 2022
• Est. primary completion date: September 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• Endothelial Dysfunction
• Inflammation
• Thrombosis

Intervention

Drug:
• Sulodexide
Sulodexide 250 LSU 1 oral capsule twice daily for 8 weeks

Locations

Country	Name	City	State
Russian Federation	Moscow Clinical Hospital no.24	Moscow

Sponsors (1)

Lead Sponsor	Collaborator
Pirogov Russian National Research Medical University

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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