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

NCT05403359 | Completed

• 1 other identifier: 10430102110010
• Study Type: observational
• Target: 2,465
• Locations: 1 country
• Sites: 1

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.

Conditions

COVID-19

Outcome Measures

Primary Outcomes (4)

• 28-day survival (WP2-3)

  Alive at day 28 yes/no

  Day 28

• 28-day need of invasive mechanical ventilation (WP2-3)

  Need for mechanical ventilation at day 28 yes/no

  Day 28

• Need for WHO severity 6-9 (WP1)

  WHO clinical progression scale class 6: high flow nasal cannula WHO class 7-9: invasive ventilation

  From date of hospital admission up to date of hospital discharge, assessed up to 12 months

• Hospital mortality in patients who receive HFNC or invasive mechanical ventilation due to restrictions in care (WP1)

  Restrictions in care (either on medical grounds or by advance directive of the patient)

  From date of hospital admission up to date of hospital discharge, assessed up to 12 months

Secondary Outcomes (8)

• ICU mortality

  During ICU stay

• Hospital mortality

  From date of hospital admission up to date of hospital discharge, assessed up to 12 months

• Hospital length of stay

  From date of hospital admission up to date of hospital discharge, assessed up to 12 months

• ICU length of stay

  During ICU stay

• Mechanical ventilation duration

  During ICU stay

Study Arms (2)

Ward (e.g., pulmonology ward, COVID-unit, etc.),

* 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.

Drug: Steroids

Intensive Care Unit

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).

Drug: Steroids

Interventions

Steroids DRUG

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.

Intensive Care Unit; Ward (e.g., pulmonology ward, COVID-unit, etc.),

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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).

You may qualify if:

• Adult (i.e., ≥18 years)
• Hospitalized (i.e., admitted to the hospital)
• 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:
• Admitted to the ward (e.g., pulmonology ward, COVID-unit, etc.), excluding step-down units.
• 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:

You may not qualify if:

• 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.

Sponsors & Collaborators

• Henrik Endeman: lead
• Amsterdam UMC: collaborator
• OLVG: collaborator
• Isala: collaborator
• St. Antonius Hospital: collaborator
• Academisch Ziekenhuis Groningen: collaborator
• Amphia Hospital: collaborator
• Maasstad Hospital: collaborator

Study Sites (1)

Erasmus MC

Rotterdam, Netherlands

Location

Related Publications (2)

• Daenen K, Rizopoulos D, Dalm VASH, Huijben JA, Stoof SCM, Nagtzaam NMA, Dik WA, Swagemakers SMA, van der Spek PJ, Tong-Minh K, Mersha DGA, Khyali J, Juffermans NP, Gommers D, van Gorp ECM, Bos LDJ, Endeman H. Increasing inflammatory biomarkers are associated with mortality in critically ill COVID-19 patients despite anti-inflammatory treatment. Clin Exp Med. 2025 Nov 11;25(1):361. doi: 10.1007/s10238-025-01904-8.

  PMID: 41217548 DERIVED

• Daenen K, Huijben JA, Boyd A, Bos LDJ, Stoof SCM, van Willigen H, Gommers DAMPJ, Moeniralam HS, den Uil CA, Juffermans NP, Kant M, Valkenburg AJ, Pillay J, van Meenen DMP, Paulus F, Schultz MJ, Dalm VASH, van Gorp ECM, Schinkel J, Endeman H; PRoVENT- and PRoAcT-COVID Collaborative Group. Optimal Dosing and Timing of High-Dose Corticosteroid Therapy in Hospitalized Patients With COVID-19: Study Protocol for a Retrospective Observational Multicenter Study (SELECT). JMIR Res Protoc. 2023 Jun 2;12:e48183. doi: 10.2196/48183.

  PMID: 37266993 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

Steroids

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Fused-Ring Compounds; Polycyclic Compounds

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: June 1, 2022
• First Posted: June 3, 2022
• Study Start: June 1, 2022
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: April 9, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Access Criteria: Reasonable requests via email (including a protocol describing the research question and data needed) are considered.

Locations

NL (1)