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

COVID-19 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05509647
• Other study ID #: CoCo 2022-020
• Status: Completed
• Start date: January 1, 2014
• Est. completion date: October 1, 2022

Study information

• Verified date: October 2023
• Source: Leiden University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1500
• Est. completion date: October 1, 2022
• Est. primary completion date: October 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19

Intervention

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

Locations

Country	Name	City	State
Netherlands	Leiden University Medical Centre	Leiden	Zuid-holland

Sponsors (1)

Lead Sponsor	Collaborator
Leiden University Medical Center

Country where clinical trial is conducted

Netherlands, 

References & Publications (4)

Arachchillage DRJ, Kamani F, Deplano S, Banya W, Laffan M. Should we abandon the APTT for monitoring unfractionated heparin? Thromb Res. 2017 Sep;157:157-161. doi: 10.1016/j.thromres.2017.07.006. Epub 2017 Jul 6. — View Citation

Thachil J, Tang N, Gando S, Falanga A, Levi M, Clark C, Iba T, Cattaneo M. Type and dose of heparin in Covid-19: Reply. J Thromb Haemost. 2020 Aug;18(8):2063-2064. doi: 10.1111/jth.14870. Epub 2020 May 11. No abstract available. — View Citation

White D, MacDonald S, Bull T, Hayman M, de Monteverde-Robb R, Sapsford D, Lavinio A, Varley J, Johnston A, Besser M, Thomas W. Heparin resistance in COVID-19 patients in the intensive care unit. J Thromb Thrombolysis. 2020 Aug;50(2):287-291. doi: 10.1007/s11239-020-02145-0. Erratum In: J Thromb Thrombolysis. 2020 Jun 22;: — View Citation

Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, Wu Y, Zhang L, Yu Z, Fang M, Yu T, Wang Y, Pan S, Zou X, Yuan S, Shang Y. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020 May;8(5):475-481. doi: 10.1016/S2213-2600(20)30079-5. Epub 2020 Feb 24. Erratum In: Lancet Respir Med. 2020 Apr;8(4):e26. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Heparin dosage	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	Correlation between aPTT and anti-Xa values	To explore possible causes for non-correlating aPTT and Anti-Xa levels	Until end of heparin therapy or ICU discharge, whatever comes first.
Secondary	Correlation between non-correlating aPTT and Anti-Xa levels and CRP	To explore possible causes for non-correlating aPTT and Anti-Xa levels	Until end of heparin therapy or ICU discharge, whatever comes first.
Secondary	Correlation between non-correlating aPTT and Anti-Xa levels and AT plasma levels	To explore possible causes for non-correlating aPTT and Anti-Xa levels	Until end of heparin therapy or ICU discharge, whatever comes first.