Nadroparin Pharmacokinetics in Different Stages of COVID-19
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| conventional oxygen therapy Patients treated with conventional oxygen in Infectious Diseases Ward. |
Drug: Nadroparin
Subcutaneous injection of nadroparin according to the ICU guidelines for thromboprophylaxis in ICU patients.
|
| mechanical ventilation Patients who are mechanically ventilated and treated in ICU. |
Drug: Nadroparin
Subcutaneous injection of nadroparin according to the ICU guidelines for thromboprophylaxis in ICU patients.
|
| mechanical ventilation and ECMO Patients who are mechanically ventilated and on ECMO treated in ICU. |
Drug: Nadroparin
Subcutaneous injection of nadroparin according to the ICU guidelines for thromboprophylaxis in ICU patients.
|
Outcome Measures
Primary Outcome Measures
- Change in nadroparin concentration in blood measurement [6 hours]
Sequential measurement every 6 hours
- Change in anti-Xa serum level [12 hours]
Sequential measurement every 12 hours
Secondary Outcome Measures
- Volume of distribution of nadroparin [24 hours]
- Clearance of nadroparin [24 hours]
- Absorption rate of nadroparin [24 hours]
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 2nd Department of Anesthesiology and Critical Care, Medical University of Lublin | Lublin | Lubelskie | Poland | 20-059 |
Sponsors and Collaborators
- Medical University of Lublin
- Medical University of Gdansk
Investigators
- Principal Investigator: Paweł Piwowarczyk, MD PhD, Medical University of Lublin
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- KE 0254/23/2021