CORT-E2

Corticosteroid Early and Extended

Domain Lead Investigators

Domain Protocol Committee Members

Resources

Domain Description

Objective

To examine the effect of early corticosteroids in non-COVID AHRF and to examine the effect of extended corticosteroids at 10 days in both COVID and non-COVID persisting AHRF.

Population For the early domain: Adult patients admitted to the ICU for less than 72 hours receiving high flow nasal cannula, non-invasive ventilation, invasive ventilation, or extracorporeal life support for at least 4 consecutive hours for non-COVID acute hypoxemic respiratory failure with new unilateral or bilateral airspace disease on chest radiograph. For the extended domain: Adult ICU patients who have already received 10 days of corticosteroids for AHRF (either COVID-19 or other causes) with ongoing AHRF requiring HFNC, NIV, invasive ventilation, or extracorporeal life support.
Primary Endpoint 60-day mortality
Design

The intervention is being evaluated at phase III to determine superiority or futility on the domain primary endpoint. 

Control Group

Name For the early domain: Usual care without corticosteroids
Description

For the early domain: Those randomized to usual care will receive routine AHRF management without corticosteroids.  

Target sample size Up to 1,000
Participating sites All sites participating in this domain
Name For the extended domain: Usual care without additional corticosteroids
Description

For the extended domain: No additional corticosteroids

Target sample size Up to 1,000
Participating sites All sites participating in this domain

Interventions

  • Intervention Lead investigators
    Eligible states

    For Early Corticosteroids: 

    • Non-intubated
    • Low elastance (invasively ventilated)
    • High elastance (invasively ventilated)
    • Extracorporeal life support

    For Extended Corticosteroids: 

    • Low elastance (invasively ventilated)
    • High elastance (invasively ventilated)
    • Extracorporeal life support
    Description

    For Early Corticosteroids:  Patients with non-COVID AHRF will be randomized to early (within 72 hours of ICU admission) corticosteroids or usual care. The early corticosteroid arm will receive dexamethasone 20mg daily, administered parenterally for 10 days from the time of randomization; after 10 days dexamethasone will be stopped without a taper.  

    For Extended Corticosteroids: 10 additional days of dexamethasone 12mg administered parenterally. At the end of the 10 additional days, the dexamethasone dose will be halved to 6mg for 5 days (to reduce the risk of adrenal insufficiency) and then stopped.

    Stage of evaluation Phase III
    Primary endpoint

    Mortality at 60 days

    Active comparator

    For Early Corticosteroids: Usual care without corticosteroids;  For Extended Corticosteroids:  Usual care without additional corticosteroids.

    Target sample size Adapted based on pre-specified stopping rules defining superiority and futility. Maximum sample size of 1,000.
    Participating sites All sites participating in this domain