Nadroparin Pharmacokinetics in Different Stages of COVID-19

Study Overview
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Brief Summary
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Objective: The risk of thrombotic complications in critical COVID-19 patients remains extremely high, and multicenter trials failed to prove the survival benefit of escalated doses of low molecular weight heparins (LMWH) in this group. The aim of this study was to develop a pharmacokinetic model of LMWH (nadroparin calcium) according to different stages of COVID-19 severity. Design: The investigators performed a prospective observational study. Patients: Blood samples were obtained from 43 COVID-19 patients that received nadroparin and were treated with conventional oxygen therapy, mechanical ventilation, and extracorporeal membrane oxygenation. Setting: The investigators recorded clinical, biochemical, and hemodynamic variables during 72 hours of treatment. The analyzed data comprised 782 serum nadroparin concentrations and 219 anti-factor Xa levels. The investigators conducted population nonlinear mixed-effects modeling (NONMEM) and performed Monte Carlo simulations of the probability of target attainment (PTA) for reaching 0.2-0.5 IU/ml anti-Xa levels in study groups. Interventions: None. Measurements and Main Results: The investigators successfully developed a one-compartment model to describe the population pharmacokinetics of nadroparin in different stages of COVID-19. Conclusions: Different nadroparin dosing is required for patients undergoing mechanical ventilation and ECMO to achieve the same targets as those for non-critically ill patients.

Official Title
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Nadroparin Pharmacokinetics in Different Stages of COVID-19-a Prospective Observational Study.

Conditions
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Thrombosis, Nadroparin, COVID-19, Mechanical Ventilation, Anticoagulants and Bleeding Disorders

Intervention / Treatment
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* Drug: Nadroparin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients treated in the Department of Anesthesiology and Intensive Care and the Department of Infectious Diseases of a tertiary academic hospital with confirmed SARS-CoV-2 infection with a real-time reverse transcription polymerase chain reaction (RT-PCR) or an antigen test. Exclusion Criteria: Coagulation disorders at the start of the therapy.

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| conventional oxygen therapy<br>Patients treated with conventional oxygen in Infectious Diseases Ward. | Drug: Nadroparin<br>* Subcutaneous injection of nadroparin according to the ICU guidelines for thromboprophylaxis in ICU patients.<br>|
| mechanical ventilation<br>Patients who are mechanically ventilated and treated in ICU. | Drug: Nadroparin<br>* Subcutaneous injection of nadroparin according to the ICU guidelines for thromboprophylaxis in ICU patients.<br>|
| mechanical ventilation and ECMO<br>Patients who are mechanically ventilated and on ECMO treated in ICU. | Drug: Nadroparin<br>* Subcutaneous injection of nadroparin according to the ICU guidelines for thromboprophylaxis in ICU patients.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in nadroparin concentration in blood measurement | Sequential measurement every 6 hours | 6 hours | 
| Change in anti-Xa serum level | Sequential measurement every 12 hours | 12 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Volume of distribution of nadroparin |  | 24 hours | 
| Clearance of nadroparin |  | 24 hours | 
| Absorption rate of nadroparin |  | 24 hours |