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

Sponsor

Karolinska Institutet (Other)

Overall Status

Completed

CT.gov ID

NCT05256524

Collaborator

Lund University (Other)

1,520

Enrollment

Location

17.9

Actual Duration (Months)

84.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Covid19 Thromboembolism Bleeding	Drug: The effect of LMWH Diagnostic Test: Monitoring frequency of aFXa-levels

Study Design

Study Type:

Observational

Actual Enrollment :

1520 participants

Observational Model:

Cohort

Time Perspective:

Retrospective

Official Title:

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

Actual Study Start Date :

Mar 1, 2020

Actual Primary Completion Date :

May 31, 2021

Actual Study Completion Date :

Aug 29, 2021

Arms and Interventions

Arm	Intervention/Treatment
Patients with critical COVID-19 responding to LMWH treatment 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 Quantified by aFXa-levels Diagnostic Test: Monitoring frequency of aFXa-levels The frequency of aFXa-levels being sampled, analysed and integrated as a possible part of the basis for clinical decisionmaking
Patients with critical COVID-19 not responding to LMWH treatment 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 Quantified by aFXa-levels Diagnostic Test: Monitoring frequency of aFXa-levels The frequency of aFXa-levels being sampled, analysed and integrated as a possible part of the basis for clinical decisionmaking

Arm

Intervention/Treatment

Patients with critical COVID-19 responding to LMWH treatment

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

Quantified by aFXa-levels

Diagnostic Test: Monitoring frequency of aFXa-levels

The frequency of aFXa-levels being sampled, analysed and integrated as a possible part of the basis for clinical decisionmaking

Patients with critical COVID-19 not responding to LMWH treatment

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

Quantified by aFXa-levels

Diagnostic Test: Monitoring frequency of aFXa-levels

The frequency of aFXa-levels being sampled, analysed and integrated as a possible part of the basis for clinical decisionmaking

Outcome Measures

Primary Outcome Measures

Mortality [90 days from ICU admission]
90-day mortality

Secondary Outcome Measures

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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