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Optimale dosering en timing van corticosteroïden bij gehospitaliseerde patiënten met COVID-19

Projectomschrijving

Patiënten met COVID-19 opgenomen in het ziekenhuis hebben een vaak overmatige ontstekingsreactie. Het gebruik van het ontstekingsremmende corticosteroïd dexamethason is daarom de hoeksteen van de behandeling van deze patiënten. Helaas blijft er een groep patiënten over die onvoldoende reageert op deze behandeling.

Doel

Het doel van deze studie is om te onderzoeken of patiënten met onvoldoende respons op de standaard behandeling met ontstekingsremmers baat hebben bij een hogere dosering, en wat het juiste moment is om deze verhoogde dosering toe te dienen.

Onderzoeksopzet

Dit project is een samenwerking tussen een aantal ziekenhuizen in Nederland, waarbij wat betreft steroïden behandeling er lokale verschillen zijn tussen moment van toedienen en dosering. Door data van een groot aantal patiënten samen te voegen en de bestaande praktijkvariatie in kaart te brengen en behandelingsuitkomsten te onderzoeken hopen de onderzoekers meer inzicht te krijgen in de juiste dosering en tijdstip van toedienen van steroïden in de behandeling van COVID-19. Daarnaast zal er ook gekeken worden of er bepaalde laboratorium markers zijn in het bloed of in de longen van de patiënten die voorspellen welke patiënten baat hebben bij een hoge dosis steroïden.

Uitvoerende partijen

Erasmus MC, Amsterdam UMC – locatie AMC, OLVG locatie West, St. Antonius Ziekenhuis, Isala Klinieken

Context

Dit onderzoek is 1 van de studies op het gebied van onderzoek naar optimale medisch-specialistische zorg bij COVID-19. De onderzoeken hebben als doel het beantwoorden van belangrijke kennishiaten op gebied van behandeling. ZonMw faciliteert deze onderzoeken in het COVID-19 deelprogramma Behandeling om een bijdrage te leveren aan het bevorderen van optimale zorg voor COVID-19. De kennishiaten zijn geïdentificeerd door de Multidisciplinaire Wetenschapscommissie COVID-19 van de Federatie Medisch Specialisten (FMS).

Meer informatie

Hoofdaanvrager: H. Endeman (Erasmus MC)
Projectleider en penvoerder: J. Schinkel (Amsterdam UMC)

Verslagen


Samenvatting van de aanvraag

Title Optimal dosing and timing of corticosteroids in hospitalized patients with COVID-19 Backgroud and Hypothesis COVID-19 has a three-phasic pattern. Patients who are hospitalized with COVID-19 and treated on the normal ward are mainly in stage II, ICU patients are in stage II and III. All patients in need of oxygen therapy, the main reason for hospitalization, are being treated with dexamethasone, regardless of their level of inflammation, severity of disease (COVID-19 on the ward to COVID-associated ARDS; C-ARDS) or way of oxygen therapy. Patients hospitalized for COVID-19 and treated on the ward are mainly in phase 2(a) and in the ICU in 3. There therapy is protocolized and consists of dexamethasone 6 mg for 10 days combined with tozilicumab in majority of the patients. Therapy will be homogenous unless patients have progressive disease while being treated with dexamethasone or at the end of the 10 day cure. A fraction of these patients will stay on the ward, as (invasive) mechanical ventilation is not required. The majority of them is in the ICU. For both, there may be an indication for escalation of steroid therapy, for example because they suffer from an organizing pneumonia of moderate to severe C-ARDS. The objective of the study proposed here is to answer the following questions formulated in 4 work-packages (WPs) Intervention and outcome WP1-ward: Do high-dose steroids improve outcome in dexamethasone-unresponsive COVID-19 patients on the ward compared to no steroids? Background: Dexamethasone is the initial therapy of patients hospitalized with COVID-19 on the ward. Most of these patients are in phase II of disease. Some of these patients have progressive disease after finishing dexamethasone cure. These dexamethasone unresponsive COVID-19 patients can be treated with high-dose corticosteroids Intervention: Patients admitted to the ICU with moderate/severe ARDS are stratified in high-dose steroids (> 6 mg dexamethasone or equivalent steroid (exposed) or dexamethasone 6 mg (unexposed) up to 72 hour after admission. Some of the patients admitted to the ICU may have already been treated with dexamethasone 6 mg on the ward, which will be accounted for in analysis. Outcome measures: 28-day survival, 28-day hospital free days, 28-day need of invasive mechanical ventilation. WP2-ICU admission: Do high-dose steroids improve outcome in patients admitted to the ICU with moderate/severe C-ARDS compared to dexamethasone 6 mg? Background: Patients admitted to the ICU suffer from moderate/severe ARDS and are mainly in phase 3. They are primary treated with dexamethasone 6 mg. Some ICUs treated these patients per protocol or on individual basis with higher dose of steroids, as they assess the need of ICU-therapy as dexamethasone failure or as a marker of higher level of inflammation. Intervention: After 10 days of dexamethasone therapy patients are being stratified in high-dose steroids (> 6 mg dexamethasone or equivalent steroid (exposed) or no steroids (unexposed) up to day 28. Dosing and timing are important covariates to consider in analysis. Outcome measures: 28-day survival and 28-day ventilation free days. Within this WP latent class analysis will be performed to identify subtypes of C-ARDS and their relation with effect of high-dosed corticosteroid therapy. WP3-ICU late: Do high-dose steroids improve outcome in ICU patients with moderate/severe C-ARDS after dexamethasone? Background: Patients admitted to ICU with C-ARDS with progression of disease after treatment with dexamethasone. Most of these patients fulfil the criteria of moderate to severe C-ARDS. There are only guidelines for the use of high-dose corticosteroids for non-C-ARDS in this condition. There is large heterogeneity in the use of high-dose steroids in C-ARDS, and timing of this intervention (red arrows) Intervention: After 10 days of dexamethasone therapy patients are being stratified in high-dose steroids (> 6 mg dexamethasone or equivalent steroid (exposed) or no steroids (unexposed) up to day 28. Dosing and timing are important covariates to consider in analysis. Outcome measures: similar to WP2 WP4-biobank: Can biomarkers help to predict outcome to (high dosed) steroid therapy? Background: The clinical course of COVID-19 is characterized by an initial phase of viral pneumonia followed by immunothrombosis and hyperinflammation to diffuse alveolar damage or organising pneumonia eventually ending with fibrosis or death. These phases are partly reflected by morphology (CT-thorax) and laboratory markers associated with the pathophysiological phenomena described above. This work package is divided in two separate studies (WP4a and WP4b). In WP4a markers that can be measured using commercially and general available (immuno-)assays will be determined in serum and/or in BALF using a Luminex multiplex assay which targets a panel of inflammatory, coagulation and endothelial dysfunction markers.

Onderwerpen

Kenmerken

Projectnummer:
10430102110010
Looptijd: 70%
Looptijd: 70 %
2022
2024
Onderdeel van programma:
Projectleider en penvoerder:
J. Schinkel
Verantwoordelijke organisatie:
Erasmus Medisch Centrum