Observational, Retrospective Study to Evaluate Coagulation Changes and the Influence of Antithrombin III Treatment in Patients With Severe COVID-19 Infection

Multinational, Observational, Retrospective Study to Evaluate Coagulation Changes and the Influence of Antithrombin III Treatment in Patients With Severe COVID-19 Infection

Multicentre, multinational, non-interventional, observational, retrospective, patient record study to evaluate changes in coagulation parameters in patients with severe COVID-19 infection receiving/not treatment with antithrombin (AT) III

Study Overview

• Status: Completed
• Conditions: Covid19
• Intervention / Treatment: Drug: Antithrombin III

• Study Type: Observational
• Enrollment (Actual): 300

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria, 6020
    • Octapharma Research Site
  • Wien, Austria, 1090
    • Octapharma Research Site
• France
  • Strasbourg, France
    • Octapharma Research Site
• Germany
  • Aachen, Germany, 52074
    • Octapharma Research Site
  • Essen, Germany, 45147
    • Octapharma Research Site
• Sweden
  • Stockholm, Sweden, 17176
    • ECMO Centre Karolinska

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

A target of 150 patients (male and female) hospitalised with severe COVID-19 infection and having required oxygen therapy (including those requiring a ventilator, central venous catheter or ECMO) will be included into this study. A control group of matched numbers of non-COVID-19 patients hospitalised and having required oxygen therapy will be included.

Description

For Sites in Austria:

Inclusion Criteria:

For the +COVID-19 group:

• Confirmed COVID-19 positive test result OR extremely high likelihood of COVID-19 infection (e.g., family member or other person co-habiting with subject with a documented infection; passenger from cruise ship with +COVID- 19)
• Hospitalisation for severe COVID-19 infection until 01.06.2020
• COVID-19 patients having required oxygen therapy as per local guidelines (including those requiring a ventilator, central venous catheter or ECMO)

For the control group:

• Hospitalisation for any disease other than COVID-19 infection until end 2019 (31.12.2019)
• Patients having required oxygen therapy as per local guidelines (including those requiring a ventilator, central venous catheter or ECMO)

Exclusion Criteria:

• Known hypersensitivity or allergic reaction to ATIII
• Participation in any interventional trial during the time of individual observational period (date of hospitalisation to the date of removal of oxygen therapy or death, whichever occurred first)
• Pregnant women

For Sites in France:

Inclusion Criteria:

For the +COVID-19 group:

• Confirmed COVID-19 positive test result OR extremely high likelihood of COVID-19 infection (e.g., family member or other person co-habiting with subject with a documented infection; passenger from cruise ship with +COVID-19)
• Hospitalisation for severe COVID-19 infection and discharged from the hospital or died before start of documentation. COVID-19 patients having required oxygen therapy as per local guidelines (including those requiring a ventilator, central venous catheter or ECMO)

For the control group:

• Hospitalisation for any disease other than COVID-19 infection until end 2019 (31.12.2019)
• Patients having required oxygen therapy as per local guidelines (including those requiring a ventilator, central venous catheter or ECMO)

Exclusion Criteria:

• Known hypersensitivity or allergic reaction to ATIII
• Participation in any interventional trial during the time of individual observational period (date of hospitalisation to the date of removal of oxygen therapy or death, whichever occurred first)
• Pregnant women

For sites in Germany:

Inclusion Criteria:

For the +COVID-19 group:

• Confirmed COVID-19 positive test result OR extremely high likelihood of COVID-19 infection (e.g., family member or other person co-habiting with subject with a documented infection; passenger from cruise ship with +COVID-19)
• Hospitalisation for severe COVID-19 infection until 01.02.2021.
• COVID-19 patients having required oxygen therapy as per local guidelines (including those requiring a ventilator, central venous catheter or ECMO)

For the control group:

• Hospitalisation for any disease other than COVID-19 infection until end 2019 (31.12.2019)
• Patients having required oxygen therapy as per local guidelines (including those requiring a ventilator, central venous catheter or ECMO)

Exclusion Criteria:

• Known hypersensitivity or allergic reaction to ATIII
• Participation in any interventional trial during the time of individual observational period (date of hospitalisation to the date of removal of oxygen therapy or death, whichever occurred first)
• Pregnant women

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
COVID-19 patients who had received treatment with ATIII; Patient records of patients hospitalised for severe COVID-19 infection until 01.06.2020 that required oxygen therapy will be used to retrospectively gather baseline demographic data (age, gender, height, weight, ethnicity/race, blood group, rhesus factor) and comorbidities. Records will also be used to retrospectively gather information on routine coagulation and laboratory parameters measured as per local protocols (including where available: AT, aPTT, PT, Quick, INR, , fibrinogen, D-dimers, haemoglobin levels, and platelet count), and thromboembolic complications and bleeding events that occurred during the individual observational treatment period. Patients will be grouped into 2 cohorts; those that received treatment with ATIII and those that did not. ATIII was administered as per local guidelines at each institute.	Drug: Antithrombin III; Antithrombin III
COVID-19 patients who had not received treatment with ATIII; Patient records of patients hospitalised for severe COVID-19 infection until 01.06.2020 that required oxygen therapy will be used to retrospectively gather baseline demographic data (age, gender, height, weight, ethnicity/race, blood group, rhesus factor) and comorbidities. Records will also be used to retrospectively gather information on routine coagulation and laboratory parameters measured as per local protocols (including where available: AT, aPTT, PT, Quick, INR, , fibrinogen, D-dimers, haemoglobin levels, and platelet count), and thromboembolic complications and bleeding events that occurred during the individual observational treatment period. Patients will be grouped into 2 cohorts; those that received treatment with ATIII and those that did not. ATIII was administered as per local guidelines at each institute.
Non-COVID-19 patients who had received treatment with ATIII; A control group will be used to gather comparative data in non-COVID-19 patients. Data will be gathered retrospectively from patient records for severely ill patients who received oxygen therapy for non-COVID-19 infection until end 2019 (31.12.2019). Control group will also be grouped into 2 cohorts for those having received/ having not received ATIII treatment.	Drug: Antithrombin III; Antithrombin III
Non-COVID-19 patients who had not received treatment with ATIII; A control group will be used to gather comparative data in non-COVID-19 patients. Data will be gathered retrospectively from patient records for severely ill patients who received oxygen therapy for non-COVID-19 infection until end 2019 (31.12.2019). Control group will also be grouped into 2 cohorts for those having received/ having not received ATIII treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antithrombin Levels	Levels of AT in severely ill COVID-19 positive patients receiving/not receiving ATIII treatment	throughout hospitalization, approximately 1-3 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
aPPT Levels	aPPT Levels in severely ill COVID-19 patients receiving/not receiving ATIII treatment and compared to control group	throughout hospitalization, approximately 1-3 weeks
PT Levels	PT Levels in severely ill COVID-19 patients receiving/not receiving ATIII treatment and compared to control group	throughout hospitalization, approximately 1-3 weeks
Quick Levels	Quick Levels in severely ill COVID-19 patients receiving/not receiving ATIII treatment and compared to control group	throughout hospitalization, approximately 1-3 weeks
INR Levels	INR Levels in severely ill COVID-19 patients receiving/not receiving ATIII treatment and compared to control group	throughout hospitalization, approximately 1-3 weeks
D-dimer Levels	D-dimer Levels in severely ill COVID-19 patients receiving/not receiving ATIII treatment and compared to control group	throughout hospitalization, approximately 1-3 weeks
Fibrinogen Levels	Fibrinogen Levels in severely ill COVID-19 patients receiving/not receiving ATIII treatment and compared to control group	throughout hospitalization, approximately 1-3 weeks
Haemoglobin Levels	Haemoglobin Levels in severely ill COVID-19 patients receiving/not receiving ATIII treatment and compared to control group	throughout hospitalization, approximately 1-3 weeks
Platelet Levels	Platelet Levels in severely ill COVID-19 patients receiving/not receiving ATIII treatment and compared to control group	throughout hospitalization, approximately 1-3 weeks
Thromboembolic complications and bleeding events between groups	Comparison of the occurrence of thromboembolic complications and bleeding events between groups	throughout hospitalization, approximately 1-3 weeks
Comparison of the duration of requirement for oxygen therapy, and invasive ventilation support or ECMO between groups	Comparison of the duration of requirement for oxygen therapy, and invasive ventilation support or ECMO between groups	throughout hospitalization, approximately 1-3 weeks
Hospital length of stay	Hospital length of stay between groups	throughout hospitalization, approximately 1-3 weeks
Number of days in ICU	Number of days in ICU between groups	throughout hospitalization, approximately 1-3 weeks
Number of days requiring oxygenation	Number of days requiring oxygenation between groups	throughout hospitalization, approximately 1-3 weeks
Discharge disposition	Discharge disposition between groups	throughout hospitalization, approximately 1-3 weeks
Mortality	Mortality between groups	throughout hospitalization, approximately 1-3 weeks

Collaborators and Investigators

• Sponsor: Octapharma

Study record dates

Study Major Dates

• Study Start (Actual): October 19, 2020
• Primary Completion (Actual): September 27, 2022
• Study Completion (Actual): September 27, 2022

Study Registration Dates

• First Submitted: November 19, 2020
• First Submitted That Met QC Criteria: December 2, 2020
• First Posted (Actual): December 3, 2020

Study Record Updates

• Last Update Posted (Estimated): October 9, 2023
• Last Update Submitted That Met QC Criteria: October 6, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Serine Proteinase Inhibitors; Anticoagulants; Antithrombins; Antithrombin III
• Other Study ID Numbers: ATN105

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No