StEroids in hospitaLized patiEnts With Covid-19 in The Netherlands.

Completed

• Conditions: COVID-19
• Interventions: Drug: Steroids

• Registration Number: NCT05403359
• Lead Sponsor: Henrik Endeman

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-06-01
• Study First Submitted: 2022-06-01
• Study First Submitted QC: 2022-06-02
• Study First Posted: 2022-06-03
• Primary Completion: 2023-12-01
• Study Completion: 2023-12-01
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-07
• Last Update Posted: 2025-04-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 2465

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Ward (e.g., pulmonology ward, COVID-unit, etc.),	Steroids	* WP1A: Patients with WHO clinical progression scale class 4-5 (i.e., no oxygen therapy) admitted to the ward with laboratory-confirmed COVID-19. * WP1B: Adult patients admitted to the ward with laboratory-confirmed COVID-19 and on at least oxygen therapy.
Intensive Care Unit	Steroids	Adult patients (≥18 years) admitted to the ICU with laboratory-confirmed COVID-19 and acute respiratory distress syndrome (ARDS) according to the Berlin definition criteria (i.e., receiving invasive mechanical ventilation).

Primary Outcome Measures

Name	Time	Method
28-day survival (WP2-3)	Day 28	Alive at day 28 yes/no
Hospital mortality in patients who receive HFNC or invasive mechanical ventilation due to restrictions in care (WP1)	From date of hospital admission up to date of hospital discharge, assessed up to 12 months	Restrictions in care (either on medical grounds or by advance directive of the patient)
28-day need of invasive mechanical ventilation (WP2-3)	Day 28	Need for mechanical ventilation at day 28 yes/no
Need for WHO severity 6-9 (WP1)	From date of hospital admission up to date of hospital discharge, assessed up to 12 months	WHO clinical progression scale class 6: high flow nasal cannula WHO class 7-9: invasive ventilation

Secondary Outcome Measures

Name	Time	Method
ICU length of stay	During ICU stay	The number of days from the date of ICU admission to date of ICU discharge or death
Mechanical ventilation duration	During ICU stay	Total duration of mechanical ventilation in days
Ventilator free days and alive	Day 28	Number of ventilator free days at day 28
Hospital mortality	From date of hospital admission up to date of hospital discharge, assessed up to 12 months	In-hospital death including date
Rate of general systemic complications during hospital stay	From date of hospital admission up to date of hospital discharge, assessed up to 12 months	Myocardial infarction, deep venous thrombosis, pulmonary embolus, hyperglycemia, hypoglycemia, acute kidney injury, delirium, sepsis
ICU mortality	During ICU stay	Death at ICU including date
Hospital length of stay	From date of hospital admission up to date of hospital discharge, assessed up to 12 months	The number of days from the date of hospital admission to date of hospital discharge or death
Rate of respiratory and inflammatory complications during hospital stay	From date of hospital admission up to date of hospital discharge, assessed up to 12 months	Aspergillus, Herpes simplex virus (HSV),Cytomegalovirus (CMV), Ventilator-associated pneumonia (VAP), Catheter-related bloodstream infection (CRBSI)

Trial Locations

Locations (1)

Erasmus MC; 🇳🇱 Rotterdam, Netherlands