Nadroparin Pharmacokinetics in Different Stages of COVID-19

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

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.

Study Overview

• Status: Completed
• Conditions: COVID-19; Thrombosis; Mechanical Ventilation; Anticoagulants and Bleeding Disorders; Nadroparin
• Intervention / Treatment: Drug: Nadroparin

• Study Type: Observational
• Enrollment (Actual): 43

Contacts and Locations

Study Locations

• Poland
  • Lubelskie
    • Lublin, Lubelskie, Poland, 20-059
      • 2nd Department of Anesthesiology and Critical Care, Medical University of Lublin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

First group (Group 1) consisted of 14 patients treated with conventional oxygen therapy only in the infectious diseases department. The second group (Group 2) consisted of 14 mechanically ventilated patients treated in the ICU, and the third group (Group 3) was formed by 15 patients supported with extracorporeal membrane oxygenation (ECMO) and mechanically ventilated in the ICU. The investigators used surviving sepsis campaign guidelines for COVID-19 for the escalation of treatment in the study population.

Description

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

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	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.

What is the study measuring?

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	Time Frame
Volume of distribution of nadroparin	24 hours
Clearance of nadroparin	24 hours
Absorption rate of nadroparin	24 hours

Collaborators and Investigators

• Sponsor: Medical University of Lublin
• Collaborators: Medical University of Gdansk
• Investigators: Principal Investigator: Paweł Piwowarczyk, MD PhD, Medical University of Lublin

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2021
• Primary Completion (Actual): February 10, 2022
• Study Completion (Actual): April 15, 2022

Study Registration Dates

• First Submitted: November 10, 2022
• First Submitted That Met QC Criteria: November 17, 2022
• First Posted (Actual): November 18, 2022

Study Record Updates

• Last Update Posted (Actual): November 18, 2022
• Last Update Submitted That Met QC Criteria: November 17, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Hematologic Diseases; Hemorrhagic Disorders; Embolism and Thrombosis; COVID-19; Hemostatic Disorders; Blood Coagulation Disorders; Thrombosis; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Nadroparin
• Other Study ID Numbers: KE 0254/23/2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No