Unfractionated Heparin in COVID-19 and Non-COVID-19 Patients

October 3, 2023 updated by: edejonge, Leiden University Medical Center

Unfractionated Heparin in COVID-19 and Non-COVID-19 Patients - an Observational Study.

The majority of ICU patients with COVID-19 show profound activation of coagulation, potentially resulting in thromboembolic events. In the treatment of these thromboembolic events it seemed that very high dosages of unfractionated heparin were necessary to achieve therapeutic values of aPTT and anti-Xa levels. The aim of this study is to explore whether heparin dosages are higher in COVID-19 patients compared to non-COVID-19 patients, to determine the correlation between aPTT and anti-Xa values and to explore possible causes for non-correlating aPTT and anti-Xa, including CRP and AT plasma levels.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

CoVID-19 is a viral disease caused by SARS-CoV-2 virus that may affect many organ systems. Patients with severe disease almost invariably have profound pulmonary inflammation and may require mechanical ventilation and prolonged ICU admission. Mortality in ICU patients may be up to 50%. In the majority of patients with CoVID-19 in the ICU, profound activation of coagulation is present as reflected by d-dimer levels up to 20.000 mg/L or higher. Patients with proven pulmonary thrombosis are commonly treated with unfractionated heparin (UFH). Typically, it seemed that very high dosages of UFH were necessary to achieve therapeutic values of aPTT and anti-Xa levels in COVID-19 patients. Though, the question remains whether dosages given in COVID-19 patients were indeed extravagant compared to non-COVID-19 patients and what potential causes of these high dosages might be. Earlier research already implied that APTT, which is a primarily used parameter to dose UFH, is not accurate and rather anti-Xa levels should be used. Other potential reasons for the high doses are that COVID-19 patients show signs of heparin resistance, possible due to high inflammation parameters. As overdosing of heparin can lead to serious bleeding complications, more understanding on heparin dosage, e.g. parameters to rely on and potential influencing factors, in COVID-19 patients is needed. The primary objective of this study is to determine whether heparin dosages are higher in COVID-19 patients compared to non COVID-19 patients. The secondary objective is to determine the correlation between aPTT and anti-Xa values and to explore possible causes for non-correlating aPTT and anti-Xa, including CRP and AT plasma levels.

Study Type

Observational

Enrollment (Actual)

1500

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
    • Zuid-holland
      • Leiden, Zuid-holland, Netherlands, 2333ZA
        • Leiden University Medical Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

Patients admitted to the ICU in the above mentioned periods of time and in need for unfractionated heparin treatment are eligible to participate in the study. There is no selection bias: all patients fulfilling the entry criteria will be included.

Description

Inclusion Criteria Covid-19 group:

  • Covid-19 disease proven by PCR of nose- or airway sample
  • Age ≥ 18 years
  • Admitted to the ICU from the 15th of March 2020 until 1st of January 2022
  • Treated with unfractionated heparin aiming at aPTT 60-80 sec and/or anti-Xa level 0.3-0.7 iE/ml

Inclusion Criteria non-Covid-19 group:

  • Age ≥ 18 years
  • Admitted to the ICU between the 1st of January 2014 and 1st of January 2020
  • Treated with unfractionated heparin aiming at aPTT 60-80 sec and/or anti-Xa level 0.3-0.7 iE/ml

Exclusion Criteria:

- Treatment with anticoagulants other than UFH or fibrinolytics

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Covid-19 patients
Adult patients treated with unfractionated heparin aiming at aPTT 60-80 sec and/or anti-Xa level 0.3-0.7 iE/ml. All patients have Covid-19 proven by PCR or nose- or airway swab. Patients admitted to the ICU from the 15th of March 2020 until January 2022.
Drug: Unfractionated heparin
Patients are treated with unfractionated heparin aiming at aPTT 60-80 sec and/or anti-Xa levels of 0.3-0.7 iE/ml
non-COVID-19 patients
Adult patients treated with unfractionated heparin aiming at aPTT 60-80 sec and/or anti-Xa level 0.3-0.7 iE/ml. Patients admitted to the ICU between the 1st of January 2014 and the 1st of January 2020 are included.
Drug: Unfractionated heparin
Patients are treated with unfractionated heparin aiming at aPTT 60-80 sec and/or anti-Xa levels of 0.3-0.7 iE/ml

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Heparin dosage
Time Frame: Until end of heparin therapy or ICU discharge, whatever comes first.
To determine whether heparin dosages are higher in COVID-19 patients compared to non COVID-19 patients.
Until end of heparin therapy or ICU discharge, whatever comes first.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation between aPTT and anti-Xa values
Time Frame: Until end of heparin therapy or ICU discharge, whatever comes first.
To explore possible causes for non-correlating aPTT and Anti-Xa levels
Until end of heparin therapy or ICU discharge, whatever comes first.
Correlation between non-correlating aPTT and Anti-Xa levels and CRP
Time Frame: Until end of heparin therapy or ICU discharge, whatever comes first.
To explore possible causes for non-correlating aPTT and Anti-Xa levels
Until end of heparin therapy or ICU discharge, whatever comes first.
Correlation between non-correlating aPTT and Anti-Xa levels and AT plasma levels
Time Frame: Until end of heparin therapy or ICU discharge, whatever comes first.
To explore possible causes for non-correlating aPTT and Anti-Xa levels
Until end of heparin therapy or ICU discharge, whatever comes first.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Leiden University Medical Center

Investigators

  • Principal Investigator: Evert de Jonge, MD, PhD, Leiden University Medical Centre

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2014

Primary Completion (Actual)

October 1, 2022

Study Completion (Actual)

October 1, 2022

Study Registration Dates

First Submitted

April 25, 2022

First Submitted That Met QC Criteria

August 19, 2022

First Posted (Actual)

August 22, 2022

Study Record Updates

Last Update Posted (Actual)

October 5, 2023

Last Update Submitted That Met QC Criteria

October 3, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CoCo 2022-020

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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