Is Anti-Factor Xa Associated With Outcome in Patients With Critical COVID-19 on Low-Molecular-Weight Heparin?

Study Overview
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Brief Summary
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Patients with critical COVID-19 are hyper-coagulable and optimal thromboprophylaxis treatment differs with stage and severity. The most commonly used drug for thromboprophylaxis in the intensive care unit (ICU) is low-molecular-weight heparin (LMWH). In contrast to unfractionated heparins, the effects of LMWH usually do not require monitoring. Exceptions from this are when elimination of LMWH is impaired, extremes in age and weight, to identify deviations from predicted pharmacokinetics, and if there is an unexpected clinical response. The unexpected high incidence of thromboembolic complications among patients with critical COVID-19 compared to critically ill non-COVID-19 patients could motivate monitoring. The activity of LMWH is monitored by quantifying the presence of anti-Factor Xa (aFXa). The aim of this study is to investigate if the level and the monitoring frequency of aFXa is associated to mortality, thrombosis and bleeding in patients with critical COVID-19 treated with LMWH and therefore could be used as a potential tool to guide LMWH-treatment.

Official Title
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Is Anti-Factor Xa Associated With Mortality, Thromboembolism and Bleeding in Patients With Critical COVID-19 Patients on Low-Molecular-Weight Heparin?

Conditions
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Covid19, Thromboembolism, Bleeding

Intervention / Treatment
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* Drug: The effect of LMWH
* Diagnostic Test: Monitoring frequency of aFXa-levels


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with critical COVID-19 and respiratory failure Positive SARS-CoV-2 test LMWH-effect monitored by aFXa, as a trough or peak value, after at least four doses at a twice daily regime Exclusion Criteria: Diagnosed thromboembolism or major bleeding during their COVID-illness prior to ICU-admission or as a reason or contributing factor for the ICU-admission. Transferred to or from an ICU in other hospital/region making data collection regarding baseline data/outcomes not possible

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with critical COVID-19 responding to LMWH treatment<br>Responders are defined as patient who achieve aFXa-levels, peak or trough, within target-range as excepted from the given dose of LMWH. | Drug: The effect of LMWH<br>* Quantified by aFXa-levels<br>Diagnostic Test: Monitoring frequency of aFXa-levels<br>* The frequency of aFXa-levels being sampled, analysed and integrated as a possible part of the basis for clinical decisionmaking<br>|
| Patients with critical COVID-19 not responding to LMWH treatment<br>Non-responders are defined as patients who do not achieve aFXa-levels, peak or trough, within target-range as excepted from the given dose of LMWH. | Drug: The effect of LMWH<br>* Quantified by aFXa-levels<br>Diagnostic Test: Monitoring frequency of aFXa-levels<br>* The frequency of aFXa-levels being sampled, analysed and integrated as a possible part of the basis for clinical decisionmaking<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | 90-day mortality | 90 days from ICU admission | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Thromboembolic events | Thromboembolic events are defined as the cumulative proportion of pulmonary embolism (PE), ischemic stroke and deep venous thrombosis (DVT). PE must be verified by computed tomography or by clinical suspicion as cause of deterioration combined with findings of acute strain of the right heart on echocardiography. Ischemic stroke must be verified by computed tomography. DVT must by verified by ultrasound or by computed tomography. | 28 days from ICU-admission | 
| Bleeding events | Bleeding events are categorized according to the World health organization (WHO) bleeding scale: 1) Petechiae, tissue hematoma, oropharyngeal bleeding, 2) Mild blood loss, hematemesis, macroscopic hematuria, hemoptysis, joint bleeding, 3) Gross blood loss requiring red blood cell transfusion and/or hemodynamic instability, 4) Debilitating blood loss, severe hemodynamic instability, fatal bleeding, or central nervous system bleeding. | 28 days from ICU-admission | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Low-molecular-weight Heparin, Anti-Factor Xa, Critical Care