Nadroparin Pharmacokinetics in Different Stages of COVID-19

NCT05621915 | Completed FDA Drug

• 1 other identifier: KE 0254/23/2021
• Study Type: observational
• Target: 43
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• Volume of distribution of nadroparin

  24 hours

• Clearance of nadroparin

  24 hours

• Absorption rate of nadroparin

  24 hours

Study Arms (3)

conventional oxygen therapy

Patients treated with conventional oxygen in Infectious Diseases Ward.

Drug: Nadroparin

mechanical ventilation

Patients who are mechanically ventilated and treated in ICU.

Drug: Nadroparin

mechanical ventilation and ECMO

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

Drug: Nadroparin

Interventions

Nadroparin DRUG

Subcutaneous injection of nadroparin according to the ICU guidelines for thromboprophylaxis in ICU patients.

conventional oxygen therapy; mechanical ventilation; mechanical ventilation and ECMO

Eligibility Criteria

• Sex: all
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• Coagulation disorders at the start of the therapy.

Sponsors & Collaborators

• Medical University of Lublin: lead
• Medical University of Gdansk: collaborator

Study Sites (1)

2nd Department of Anesthesiology and Critical Care, Medical University of Lublin

Lublin, Lublin Voivodeship, 20-059, Poland

Location

Related Publications (1)

• Piwowarczyk P, Szczukocka M, Cios W, Okunska P, Raszewski G, Borys M, Wiczling P, Czuczwar M. Population Pharmacokinetics and Probability of Target Attainment Analysis of Nadroparin in Different Stages of COVID-19. Clin Pharmacokinet. 2023 Jun;62(6):835-847. doi: 10.1007/s40262-023-01244-4. Epub 2023 Apr 25.

  PMID: 37097604 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples

MeSH Terms

Conditions

Thrombosis; COVID-19; Hemostatic Disorders

Interventions

Nadroparin

Condition Hierarchy (Ancestors)

Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• Paweł Piwowarczyk, MD PhD

  Medical University of Lublin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 10, 2022
• First Posted: November 18, 2022
• Study Start: February 1, 2021
• Primary Completion: February 10, 2022
• Study Completion: April 15, 2022
• Last Updated: November 18, 2022

Record last verified: 2022-11

Locations

PL (1)