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

Completed

• Conditions: Covid19; Bleeding; Thromboembolism
• Interventions: Drug: The effect of LMWH; Diagnostic Test: Monitoring frequency of aFXa-levels

• Registration Number: NCT05256524
• Lead Sponsor: Karolinska Institutet

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-03-01
• Primary Completion: 2021-05-31
• Study Completion: 2021-08-29
• Status Verified: 2022-02
• Study First Submitted: 2022-02-23
• Study First Submitted QC: 2022-02-24
• Last Update Submitted: 2022-02-24
• Study First Posted: 2022-02-25
• Last Update Posted: 2022-02-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1520

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Patients with critical COVID-19 responding to LMWH treatment	Monitoring frequency of aFXa-levels	Responders are defined as patient who achieve aFXa-levels, peak or trough, within target-range as excepted from the given dose of LMWH.
Patients with critical COVID-19 not responding to LMWH treatment	Monitoring frequency of aFXa-levels	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.
Patients with critical COVID-19 responding to LMWH treatment	The effect of LMWH	Responders are defined as patient who achieve aFXa-levels, peak or trough, within target-range as excepted from the given dose of LMWH.
Patients with critical COVID-19 not responding to LMWH treatment	The effect of LMWH	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.

Primary Outcome Measures

Name	Time	Method
Mortality	90 days from ICU admission	90-day mortality

Secondary Outcome Measures

Name	Time	Method
Thromboembolic events	28 days from ICU-admission	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.
Bleeding events	28 days from ICU-admission	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.

Trial Locations

Locations (1)

Södersjukhuset; 🇸🇪 Stockholm, Sweden