Background: There are no proven therapies specific for Covid-19. The full spectrum of Covid-19 ranges from asymptomatic disease to mild respiratory tract illness to severe pneumonia, acute respiratory distress syndrome (ARDS), multiorgan failure, and death. The efficacy of corticosteroids in viral ARDS remains controversial. Methods: This is an internationally (Spain, Canada, China, USA) designed multicenter, randomized, controlled, open-label clinical trial testing dexamethasone in mechanically ventilated adult patients with established moderate-to-severe ARDS caused by confirmed Covid-19 infection, admitted in a network of Spanish ICUs. Eligible patients will be randomly assigned to receive either dexamethasone plus standard intensive care, or standard intensive care alone. Patients in the dexamethasone group will receive an intravenous dose of 20 mg once daily from day 1 to day 5, followed by 10 mg once daily from day 6 to day 10. The primary outcome is 60-day mortality. The secondary outcome is the number of ventilator-free days at 28 days. All analyses will be done according to the intention-to-treat principle.
The acute respiratory distress syndrome (ARDS) is a catastrophic illness of multifactorial
etiology characterized by a diffuse, severe inflammatory process of the lung leading to acute
hypoxemic respiratory failure requiring mechanical ventilation (MV). Pulmonary infections are
the leading causes of ARDS. Clinical and experimental research has established a strong
association between dysregulated systemic and pulmonary inflammation and progression or
delayed resolution of ARDS.
The COVID-19 pandemic is a critical moment for the world. Severe pneumonia is the main
condition leading to ARDS requiring weeks of MV with high mortality (40-60%) in COVID-19
patients. There is no specific therapy for Covid-19, although patients are receiving drugs
that are already approved for treating other diseases. There has been great interest in the
role of corticosteroids to attenuate the pulmonary and systemic damage in ARDS patients
because of their potent anti-inflammatory and antifibrotic properties. However, the efficacy
of corticosteroids in viral ARDS remains controversial.
We justify the need of this study based on the positive results of a recent clinical trial by
our group, showing that dexamethasone for 10 days was able to reduce the duration of
mechanical ventilation (MV) and increase hospital survival in patients with ARDS from
multiple causes (Villar J et al. Lancet Respir Med 2020). Dexamethasone has never been
evaluated in viral ARDS in a randomized controlled fashion. Our goal in this study is to
examine the effects of dexamethasone on hospital mortality and on ventilator-free days in
patients with moderate-to-severe ARDS due to confirmed COVID-19 infection admitted into a
network of Spanish intensive care units (ICUs).
Drug: Dexamethasone
Dexamethasone (20 mg/iv/daily/from Day 1 of randomization during 5 days, followed by 10 mg/iv/daily from Day 6 to 10 of randomization
Other Name: dexamethasone Indukern
Inclusion Criteria:
- age 18 years or older;
- positive reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay for COVID-19
in a respiratory tract sample;
- intubated and mechanically ventilated;
- acute onset of ARDS, as defined by Berlin criteria as moderate-to-severe ARDS,3 which
includes: (i) having pneumonia or worsening respiratory symptoms, (ii) bilateral
pulmonary infiltrates on chest imaging (x-ray or CT scan), (iii) absence of left
atrial hypertension, pulmonary capillary wedge pressure <18 mmHg, or no clinical signs
of left heart failure, and (iv) hypoxemia, as defined by a PaO2/FiO2 ratio of ≤200
mmHg on positive end-expiratory pressure (PEEP) of ≥5 cmH2O, regardless of FiO2.
Exclusion Criteria:
- Routine treatment with corticosteroids during the previous week irrespective of dose;
- Corticosteroid use within the previous 24 h of more than 20 mg of dexamethasone or
equivalent;
- Patients with a known contraindication to corticosteroids;
- Decision by a physician that involvement in the trial is not in the patient's best
interest;
- Pregnancy and breast-feeding;
- Participation in another therapeutic trial.
ICU, Hospital Universitari Mutua Terrassa
Terrassa, Barcelona, Spain
Hospital Universitario Dr. Negrin
Las Palmas de Gran Canaria, Las Palmas, Spain
Department of Anesthesia, Hospital Universitario de Cruces
Barakaldo, Vizcaya, Spain
Intensive Care Unit, Hospital Universitario de Cruces
Barakaldo, Vizcaya, Spain
AVI, Hospital Clinic
Barcelona, Spain
Cardiac ICU, Hospital Clinic
Barcelona, Spain
Department of Anesthesia, Hospital Clinic
Barcelona, Spain
Hepatic ICU, Hospital Clínic
Barcelona, Spain
UVIR, Hospital Clinic
Barcelona, Spain
Intensive Care Unit, Hospital General de Ciudad Real
Ciudad Real, Spain
Department of Anesthesia, Hospital Universitario La Princesa
Madrid, Spain
Intensive Care Unit, Hospital Universitario La Princesa
Madrid, Spain
Intensive Care Unit, Hospital Universitario Fundación Jiménez Díaz
Madrid, Spain
Department of Anesthesia, Hospital Universitario La Paz
Madrid, Spain
Intensive Care Unit, Hospital Universitario La Paz
Madrid, Spain
Department of Anesthesia, Hospital Universitario Virgen de Arrixaca
Murcia, Spain
Intensive Care Unit, Hospital Universitario Virgen de la Arrixaca
Murcia, Spain
Department of Anesthesia, Hospital Unversitario Montecelo
Pontevedra, Spain
Anesthesia, Hospital General Universitario de Valencia
Valencia, Spain
Department of Anesthesia, Hospital Clinico Universitario
Valencia, Spain
Intensive Care Unit, Hospital Clinico Universitario
Valencia, Spain
Department of Anesthesia, Hospital Clínico Universitario
Valladolid, Spain
Anesthesia, Hospital Universitario Río Hortega
Valladolid, Spain
Intensive Care Unit, Hospital Universitario Río Hortega
Valladolid, Spain
Jesús Villar, MD, Principal Investigator
Hospital Universitario Dr. Negrin