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

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

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.

Study Overview

• Status: Completed
• Conditions: COVID-19; Bleeding; Thrombosis Embolism
• Intervention / Treatment: Drug: Dexamethasone

• Study Type: Interventional
• Enrollment (Actual): 445
• Phase: Phase 3

Contacts and Locations

Study Locations

• Sweden
  • Stockholms Län
    • Stockholm, Stockholms Län, Sweden, 11883
      • Södersjukhuset

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dexamethasone 12 mg; 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; ATC code H02AB02; Other Names: Dexavit
Active Comparator: Dexamethasone 6 mg; 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; ATC code H02AB02; Other Names: Dexavit

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Karolinska Institutet
• Collaborators: Aarhus University Hospital; Rigshospitalet, Denmark; Linkoeping University; Aalborg University Hospital; Stockholm South General Hospital; Copenhagen Trial Unit, Center for Clinical Intervention Research; Scandinavian Critical Care Trials Group; Centre for Research in Intensive Care (CRIC)
• Investigators: Study Director: Rebecka Rubenson Wahlin, MD. PhD, Karolinska institutet södersjukhuset; Study Chair: Maria Cronhjort, MD PhD, Karolinska institutet södersjukhuset

Study record dates

Study Major Dates

• Study Start (Actual): August 27, 2020
• Primary Completion (Actual): June 20, 2021
• Study Completion (Actual): June 30, 2021

Study Registration Dates

• First Submitted: January 13, 2022
• First Submitted That Met QC Criteria: January 13, 2022
• First Posted (Actual): January 18, 2022

Study Record Updates

• Last Update Posted (Actual): June 27, 2022
• Last Update Submitted That Met QC Criteria: June 24, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: 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; COVID-19; Embolism; Thrombosis; Thromboembolism; Embolism and Thrombosis; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone
• Other Study ID Numbers: Thromboembolism COVIDSTEROID2

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