Effect of Two Different Doses of Dexamethasone in Patients With ARDS and COVID-19
- Registration Number
- NCT04663555
- Lead Sponsor
- Brno University Hospital
- Brief Summary
REMED is a prospective, phase II, open-label, randomised controlled trial testing superiority of dexamethasone 20 mg vs 6 mg. The trial aims to be pragmatic, i.e. designed to evaluate the effectiveness of the intervention in conditions that are close to real-life routine clinical practice. The study is multi-centre and will be conducted in the intensive care units (ICUs) of ten university hospitals in the Czech Republic. This is an open-label trial in which the participants and the study staff will be aware of the allocated intervention. Blinded pre-planned statistical analysis will be performed.
- Detailed Description
Since December 2019, Covid-19 virus has infected millions of people worldwide. A significant number of patients develop hyperinflammatory state affecting lungs, which may lead to the need of oxygen therapy. In most severe cases, acute respiratory distress syndrome (ARDS) develops and high flow oxygen therapy or invasive mechanical ventilation is necessary (Wu et al., 2020). Therapeutic options in Covid-19 associated ARDS patients remain limited and mortality is still excessive. Systemic corticosteroids have potential to limit hyperinflammatory response by modulating immune system. This effect is mediated mainly by binding to glucocorticosteroid receptor α (GRα)(Meduri et al., 2020). Their effectiveness was proved in heterogeneous ARDS patients recently (Villar et al., 2020). In patients with Covid-19 pneumonia in need for oxygen therapy or mechanical ventilation, dexamethasone 6 mg per day is currently recommended. This therapy is mandated by the results of RECOVERY trial (Horby et al., 2020). After this trial was published, three randomised trials comparing hydrocortisone (Angus et al., 2020; Dequin et al., 2020) or dexamethasone (Tomazini et al., 2020) against placebo were stopped prematurely. All these studies were included in the subsequent IPD metaanalysis (Sterne et al., 2020). However, dose of 6 mg of dexamethasone is currently being reappraised. The aforementioned study in non Covid-19 ARDS patients (Villar et al., 2020) used 20 mg of dexamethasone per day, which is roughly equivalent to the methylprednisolone regimen (1mg/kg/day) studied in early severe ARDS patients (Meduri et al., 2007). Only these moderate doses (80-100 mg of methylprednisolone, equivalent to 15-19 mg of dexamethasone) have full potential to modulate immune response by saturating GRα receptors (Meduri et al., 2020). Importantly, prematurely stopped CoDEX trial (Tomazini et al., 2020) comparing dexamethasone against placebo in Covid-ARDS patients, used initial daily dose of 20 mg of dexamethasone versus placebo.
In the light of these facts, 6 mg of dexamethasone given to COVID-19 patients with different severity of illness (WHO classification group 5-10) may miss important therapeutic potential or may prevent a potential deleterious effects of a full dose therapeutic corticosteroid. Authors hypothesize that the patients with moderate to severe ARDS undergoing mechanical ventilation may benefit from higher doses of dexamethasone (Villar et al., 2020; Tomazini et al., 2020; Meduri et al., 2007).
The primary objective of this study is to test the hypothesis that administration of dexamethasone 20 mg is superior over 6 mg in adult patients with moderate or severe ARDS due to confirmed COVID-19.
Primary endpoint: Number of ventilator-free days (VFDs) at 28 days after randomisation, defined as being alive and free from mechanical ventilation (more than 48 hours).
Secondary endpoints:
1. Mortality from any cause at 60 days after randomization;
2. Dynamics of inflammatory marker (CRP) change from Day 1 to Day 14;
3. WHO Clinical Progression Scale at Day 14 (range 0-10; 0 = no illness, 1-9 = increasing level of care, and 10 = death);
4. Adverse events related to corticosteroids (new infections, new thrombotic complications) until Day 28 or hospital discharge;
5. Independence at 90 days after randomization assessed by Barthel Index The long-term outcomes of this study are to assess long-term consequences on mortality and quality of life at 180 and 360 days through telephone structured interview using Barthel Index.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 235
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description DEX 20 mg Dexamethasone Patients in the intervention group after randomization will receive dexamethasone 20 mg intravenously once daily on day 1-5, followed by dexamethasone 10 mg intravenously once daily on day 6-10. DEX 6 mg Dexamethasone Patients in the control group after randomization will receive dexamethasone 6 mg day 1-10.
- Primary Outcome Measures
Name Time Method Number of ventilator-free days (VFDs) at 28 days after randomization 28 days Number of ventilator-free days (VFDs) at 28 days after randomisation, defined as being alive and free from mechanical ventilation (more than 48 hours)
- Secondary Outcome Measures
Name Time Method Mortality from any cause at 60 days after randomization 60 days WHO clinical progression scale at day 14 14 days WHO clinical progression scale (range, 0-10, where 0 = no illness, 1-9 = increasing level of care, and 10 = death) (WHO Working Group on the Clinical Characterisation and Management of COVID-19 infection, 2020) assessed at day 14
Dynamics of inflammatory marker 14 days Dynamics of inflammatory marker (CRP) change from Day 1 to Day 14
Adverse events related to corticosteroids 28 days new infections, new thrombotic complications
Functional independence 90 days Independence at 90 days after randomization assessed by Barthel Index
Trial Locations
- Locations (1)
University Hospital Brno
🇨🇿Brno, Czechia