Nadroparin Pharmacokinetics in Different Stages of COVID-19

Medical University of Lublin

Status: Completed

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

Treatments: Drug: Nadroparin

Study type: Observational

Funder types: Other

Identifiers

NCT05621915

KE 0254/23/2021

Details and patient eligibility

About

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.

Enrollment: 43 patients

Sex

Volunteers: No Healthy Volunteers

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.

Trial design

43 participants in 3 patient groups

conventional oxygen therapy

Description:

Patients treated with conventional oxygen in Infectious Diseases Ward.

Treatment:

Drug: Nadroparin

mechanical ventilation

Description:

Patients who are mechanically ventilated and treated in ICU.

Treatment:

Drug: Nadroparin

mechanical ventilation and ECMO

Description:

Patients who are mechanically ventilated and on ECMO treated in ICU.

Treatment:

Drug: Nadroparin