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

Completed

• Conditions: COVID-19; Heparin Overdose of Undetermined Intent
• Interventions: Drug: Unfractionated heparin

• Registration Number: NCT05509647
• Lead Sponsor: Leiden University Medical Center

Brief Summary

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.

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 Timeline

• Study Start: 2014-01-01
• Study First Submitted: 2022-04-25
• Study First Submitted QC: 2022-08-19
• Study First Posted: 2022-08-22
• Primary Completion: 2022-10-01
• Study Completion: 2022-10-01
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-03
• Last Update Posted: 2023-10-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1500

Inclusion Criteria

Not provided

Exclusion Criteria

• Treatment with anticoagulants other than UFH or fibrinolytics

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Covid-19 patients	Unfractionated heparin	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.
non-COVID-19 patients	Unfractionated heparin	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.

Primary Outcome Measures

Name	Time	Method
Heparin dosage	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.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Leiden University Medical Centre; 🇳🇱 Leiden, Zuid-holland, Netherlands