Rationale: In patients with COVID-19 admitted to the hospital, large heterogeneity existsin patients, timing and dosing of steroid therapy. It is unclear how to treat patientswho fail dexamethasone therapy. High-dose steroids are prescribed mainly in patients withthe most severe disease, which may be too late given the potential escalation ofpathophysiological pathways in these patients.Objectives: The main objective is to determine the most optimal form, timing and dosingof steroid therapy to reduce the morbidity and mortality of patients admitted to thehospital for COVID-19. This objective will be addressed in 4 work packages (WP): - WP-1A-ward admission: What is the effect of higher dose steroids upon hospital admission on clinical deterioration and what would be the optimal timing of increasing steroid dosage? - WP1B-ward late: Do high-dose steroids, compared to no steroids, improve outcomes in dexamethasone-unresponsive COVID-19 patients on the ward after dexamethasone 6 mg/day for 10 days? - WP2-ICU admission: Do high-dose steroids, compared to 6 mg/day dexamethasone or its equivalent, improve outcomes in patients admitted to the ICU with moderate/severe C-ARDS? - WP3-ICU late: Do high-dose steroids, compared to no steroids, improve outcomes in ICU patients with moderate/severe C-ARDS after dexamethasone 6 mg/day for 10 days? - WP4-biobank: Can biomarkers help predict outcomes after (high dosed) steroid therapy? Study design: Retrospective observational multicenter study in the Netherlands.Study population: Adult patients (≥ 18 years) hospitalized with COVID-19 will beincluded, more specifically:Intervention (if applicable): Not applicable (retrospective study design).Nature and extent of the burden and risks associated with participation, benefit andgroup relatedness: Given the retrospective nature of the study, no burden, risks orbenefits for the patient are associated with participation. The target population of thisstudy is specific to hospitalized patients with COVID-19.
Not Provided
Drug: Steroids
Description of the intervention in each of the work packages:
- WP1A admission: Steroid dose >6mg/day dexamethasone equivalent will be compared to
control (steroid = 6mg/day dexamethasone or equivalent steroid).
- WP1B late: After 10 days of dexamethasone therapy patients are stratified in
high-dose steroids (> 6 mg dexamethasone or equivalent steroid) or no steroids up to
day 28.
- WP2 ICU admission: High-dose steroids (dexamethasone >6 mg daily or equivalent
corticosteroids) compared to dexamethasone 6 mg up to 72 hours after admission
- WP3 ICU late: After dexamethasone 6 mg for 10 days patients are stratified in
high-dose steroids (dexamethasone >6 mg daily or equivalent corticosteroids) or no
steroids up to day 28.
Inclusion Criteria:
To be eligible for inclusion in any of the work packages, an individual must meet all of
the following general inclusion criteria:
1. Adult (i.e., ≥18 years)
2. Hospitalized (i.e., admitted to the hospital)
3. Laboratory-confirmed COVID-19 diagnosis (i.e., based on polymerase chain
reaction-(PCR) test)
WP1A- ward early:
(1) Patients who present with WHO clinical progression scale class 4-5 (no oxygen
therapy, Figure 5) when admitted to the ward with COVID-19.
WP1B-ward late:
1. Admitted to the ward (e.g., pulmonology ward, COVID-unit, etc.), excluding step-down
units.
2. In need of non-invasive oxygen therapy during hospital stay, including:
- Conventional oxygen therapy (COT) 1-5 L/min
- Conventional oxygen therapy (COT) 6-12 L/min
- Non-rebreather mask 12-15 L/min
- High-flow nasal cannula 16-60 L/min
- Non-invasive continuous positive airway pressure (CPAP)
- Non-invasive bilevel positive airway pressure (BiPAP)
WP2-ICU admission/ WP3-ICU late:
1. Admitted to the ICU>48 hours.*
2. Invasive mechanical ventilation during ICU stay (intubation with endotracheal tube
or tracheostomy) or extracorporeal membrane oxygenation (ECMO).
3. ARDS according to the Berlin criteria
WP4-biobank:
The study population consists of patient subsets admitted to the ICU described in WP2 and
WP3.
Exclusion Criteria:
General exclusion criteria:
- Mortality within 48 hours.*
- Opt-out (objection to participate)
Criteria indicated with an asterisk (*) may or may not be applied, depending on data
availability. These criteria will be instated if they result in excessive variation of
the outcome or exposure, or result in difficulty in generalizing to the target
population.
Erasmus MC
Rotterdam, Netherlands
Investigator: Jilske Huijben
j.a.huijben@erasmusmc.nl
Jilske Huijben, MD, PhD
+31 (010) 703 98 83
j.a.huijben@erasmusmc.nl
Not Provided