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

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

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.

Study Overview

• Status: Completed
• Conditions: Covid19; Bleeding; Thromboembolism
• Intervention / Treatment: Drug: The effect of LMWH; Diagnostic test: Monitoring frequency of aFXa-levels

• Study Type: Observational
• Enrollment (Actual): 1520

Contacts and Locations

Study Locations

• Sweden
  • Stockholm, Sweden, 11883
    • Sodersjukhuset

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All patients with critical COVID-19 and respiratory failure admitted to ICU at Södersjukhuset, Karolinska Sjukhuset and Skånes Universitetssjukhus, in Sweden, between March 1 2020 and May 31 2021 are eligible.

Patients will be included on their first admission to the ICU if admitted more than once. First admission can be replaced by the second one if the first one is considered very short/insignificant compared to the second one. If a patient is transferred from one ICU to another this will be considered the same admission but they will be grouped according to their initial ICU.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Karolinska Institutet
• Collaborators: Lund University
• Investigators: Principal Investigator: Sandra Jonmarker, MD, Stockholm South General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2020
• Primary Completion (Actual): May 31, 2021
• Study Completion (Actual): August 29, 2021

Study Registration Dates

• First Submitted: February 23, 2022
• First Submitted That Met QC Criteria: February 24, 2022
• First Posted (Actual): February 25, 2022

Study Record Updates

• Last Update Posted (Actual): February 25, 2022
• Last Update Submitted That Met QC Criteria: February 24, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Critical Care; Low-molecular-weight Heparin; Anti-Factor Xa
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Embolism and Thrombosis; COVID-19; Hemorrhage; Thromboembolism
• Other Study ID Numbers: AntiFactorXa in Covid-19

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No