Nadroparin Pharmacokinetics in Different Stages of COVID-19

Completed

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

• Registration Number: NCT05621915
• Lead Sponsor: Medical University of Lublin

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2021-02-01
• Primary Completion: 2022-02-10
• Study Completion: 2022-04-15
• Status Verified: 2022-11
• Study First Submitted: 2022-11-10
• Study First Submitted QC: 2022-11-17
• Last Update Submitted: 2022-11-17
• Study First Posted: 2022-11-18
• Last Update Posted: 2022-11-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Not specified
• Target Recruitment: 43

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
mechanical ventilation	Nadroparin	Patients who are mechanically ventilated and treated in ICU.
conventional oxygen therapy	Nadroparin	Patients treated with conventional oxygen in Infectious Diseases Ward.
mechanical ventilation and ECMO	Nadroparin	Patients who are mechanically ventilated and on ECMO treated in ICU.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Volume of distribution of nadroparin	24 hours
Clearance of nadroparin	24 hours
Absorption rate of nadroparin	24 hours

Trial Locations

Locations (1)

2nd Department of Anesthesiology and Critical Care, Medical University of Lublin; 🇵🇱 Lublin, Lubelskie, Poland