Clinical trial NCT05403359: StEroids in hospitaLized patiEnts With Covid-19 in The Netherlands.
Official title: Optimal Dosing and Timing of Corticosteroids in Hospitalized Patients With COVID-19.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: COVID-19
Lead sponsor: Erasmus Medical Center
Sponsor class: OTHER
Collaborators: name: Amsterdam UMC
name: OLVG
name: Isala
name: St. Antonius Hospital
name: Academisch Ziekenhuis Groningen
name: Amphia Hospital
name: Maasstad Hospital
First posted: 2022-06-03
Enrollment: 2465
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Adult patients (≥18 years) hospitalized with laboratory-confirmed COVID-19.The (hospitalized) study population is expected to consist mainly of older, male, obese patients who suffer from comorbidities, like hypertension, diabetes mellitus. Around 40% of these patients require invasive mechanical ventilation. The investigators will include patients from all SARS-CoV-2 epidemic waves (including the first wave).

Brief summary: Rationale: In patients with COVID-19 admitted to the hospital, large heterogeneity exists in patients, timing and dosing of steroid therapy. It is unclear how to treat patients who fail dexamethasone therapy. High-dose steroids are prescribed mainly in patients with the most severe disease, which may be too late given the potential escalation of pathophysiological pathways in these patients.

Objectives: The main objective is to determine the most optimal form, timing and dosing of steroid therapy to reduce the morbidity and mortality of patients admitted to the hospital 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 be included, more specifically:

Intervention (if applicable): Not applicable (retrospective study design).

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Given the retrospective nature of the study, no burden, risks or benefits for the patient are associated with participation. The target population of this study is specific to hospitalized patients with COVID-19.


Eligibility criteria: 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.

Primary outcomes:
measure: 28-day survival (WP2-3)
timeFrame: Day 28
measure: 28-day need of invasive mechanical ventilation (WP2-3)
timeFrame: Day 28
measure: Need for WHO severity 6-9 (WP1)
timeFrame: From date of hospital admission up to date of hospital discharge, assessed up to 12 months
measure: Hospital mortality in patients who receive HFNC or invasive mechanical ventilation due to restrictions in care (WP1)
timeFrame: From date of hospital admission up to date of hospital discharge, assessed up to 12 months
Secondary outcomes:
measure: ICU mortality
timeFrame: During ICU stay
measure: Hospital mortality
timeFrame: From date of hospital admission up to date of hospital discharge, assessed up to 12 months
measure: Hospital length of stay
timeFrame: From date of hospital admission up to date of hospital discharge, assessed up to 12 months
measure: ICU length of stay
timeFrame: During ICU stay
measure: Mechanical ventilation duration
timeFrame: During ICU stay
measure: Ventilator free days and alive
timeFrame: Day 28
measure: Rate of respiratory and inflammatory complications during hospital stay
timeFrame: From date of hospital admission up to date of hospital discharge, assessed up to 12 months
measure: Rate of general systemic complications during hospital stay
timeFrame: From date of hospital admission up to date of hospital discharge, assessed up to 12 months
Other outcomes:
Locations:
city: Rotterdam
country: Netherlands
facility: Erasmus MC
Study officials:
References: