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

COVID-19 Clinical Trial

— SELECT  

Official title:

Optimal Dosing and Timing of Corticosteroids in Hospitalized Patients With COVID-19.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05403359
• Other study ID #: 10430102110010
• Status: Recruiting
• Start date: June 1, 2022
• Est. completion date: December 2024

Study information

• Verified date: November 2023
• Source: Erasmus Medical Center
• Contact: Jilske Huijben, MD, PhD
• Phone: +31 (010) 703 98 83
• Email: j.a.huijben[@]erasmusmc.nl
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 3800
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19

Intervention

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.

Locations

Country	Name	City	State
Netherlands	Erasmus MC	Rotterdam

Sponsors (8)

Lead Sponsor	Collaborator
Henrik Endeman	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Academisch Ziekenhuis Groningen, Amphia Hospital, Isala, Maasstad Hospital, OLVG, St. Antonius Hospital

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	28-day survival (WP2-3)	Alive at day 28 yes/no	Day 28
Primary	28-day need of invasive mechanical ventilation (WP2-3)	Need for mechanical ventilation at day 28 yes/no	Day 28
Primary	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
Primary	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	ICU mortality	Death at ICU including date	During ICU stay
Secondary	Hospital mortality	In-hospital death including date	From date of hospital admission up to date of hospital discharge, assessed up to 12 months
Secondary	Hospital length of stay	The number of days from the date of hospital admission to date of hospital discharge or death	From date of hospital admission up to date of hospital discharge, assessed up to 12 months
Secondary	ICU length of stay	The number of days from the date of ICU admission to date of ICU discharge or death	During ICU stay
Secondary	Mechanical ventilation duration	Total duration of mechanical ventilation in days	During ICU stay
Secondary	Ventilator free days and alive	Number of ventilator free days at day 28	Day 28
Secondary	Rate of respiratory and inflammatory complications during hospital stay	Aspergillus, Herpes simplex virus (HSV),Cytomegalovirus (CMV), Ventilator-associated pneumonia (VAP), Catheter-related bloodstream infection (CRBSI)	From date of hospital admission up to date of hospital discharge, assessed up to 12 months
Secondary	Rate of general systemic complications during hospital stay	Myocardial infarction, deep venous thrombosis, pulmonary embolus, hyperglycemia, hypoglycemia, acute kidney injury, delirium, sepsis	From date of hospital admission up to date of hospital discharge, assessed up to 12 months