The Effect of Dexamethasone 12 mg vs 6 mg on Thromboembolic Events in Patients With Critical COVID-19

Study Overview
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Brief Summary
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Thromboembolisms (TEs) in patients with critical COVID-19 has been reported to be three times higher than for other critically ill patients. Immunothrombosis has been proposed as a plausible mechanism for COVID-19 coagulopathy. Corticosteroids improve survival in patients with critical COVID-19, and likely even more so with a higher dose. However, the evidence regarding the impact on the incidence of thromboembolic and bleeding events are currently uncharted. The aim of this study is to investigate if there is a difference in the incidence of thromboembolic events during ICU stay in patients with critical COVID-19 when treated with 12 mg dexamethasone compared to 6 mg dexamethasone.

Official Title
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The Effect of Dexamethasone 12 mg vs 6 mg on Thromboembolic Events in Patients With Critical COVID-19 - a Post-hoc Analysis of the Blinded, Randomized COVID STEROID 2 Trial

Conditions
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COVID-19, Thrombosis Embolism, Bleeding

Intervention / Treatment
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* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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All patients were recruited from the CS2-trial with following inclusion/exclusion criteria: Inclusion Criteria: confirmed SARS-CoV-2 AND requiring at least 10l/min of O2 supplementation, non-invasive mechanical ventilation for hypoxia or invasive mechanical AND Exclusion Criteria: if previously randomised to the CS2 trial if they had received corticosteroids for COVID-19 during ≥5 consecutive days or use corticosteroids in doses >6 mg dexamethasone for an indication other than COVID-19. active tuberculosis hypersensitivity to dexa-/betamethasone active fungal infection fertile woman ≤60 years of age with a positive U-HCG/P-HCG test informed consent not obtainable For the inclusion in this post-hoc analyses there is additional criteria: Inclusion Criteria: - randomised in the ICU Exclusion Criteria: established thromboembolism at randomisation established major bleeding at randomisation

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dexamethasone 12 mg<br>Intravenous bolus injection of dexamethasone 12 mg once daily in addition to standard care for up to 10 days. We will allow the use of betamethasone 12 mg at sites, where dexamethasone is not available. | Drug: Dexamethasone<br>* ATC code H02AB02<br>* Other names: Dexavit;|
| Active Comparator: Dexamethasone 6 mg<br>Intravenous bolus injection of dexamethasone 6 mg once daily in addition to standard care for up to 10 days. We will allow the use of betamethasone 6 mg at sites, where dexamethasone is not available. | Drug: Dexamethasone<br>* ATC code H02AB02<br>* Other names: Dexavit;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients discharged alive from the ICU without thromboembolic events | Number of patients discharged alive from the ICU without thromboembolic events defined as pulmonary embolism, deep venous thrombosis, ischemic stroke, myocardial infarction, transient ischemic attack, other thromboembolic events | During ICU-stay | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The cumulative proportion of thromboembolic events | The incidence of thromboembolic events defined as pulmonary embolism, deep venous thrombosis, ischemic stroke, myocardial infarction, transient ischemic attack, other thromboembolic events | During ICU-stay | 
| The cumulative proportion of bleeding events | The cumulative proportion of bleeding events defined as any type of bleeding | During ICU-stay | 
| The cumulative proportion of major bleeding events | The cumulative proportion of major bleeding event (defined as bleeding requiring transfusion of at least 2 units of Red Blood Cells (RBC) and/or intracranial bleeding and/or bleeding resulting in need for major therapeutic intervention | During ICU-stay |