Clinical trial NCT04325061: Efficacy of Dexamethasone Treatment for Patients With ARDS Caused by COVID-19
Official title: Efficacy of Dexamethasone Treatment for Patients With ARDS Caused by COVID-19
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Acute Respiratory Distress Syndrome Caused by COVID-19
Keywords: ARDS
COVID-19
multiple system organ failure
Lead sponsor: Dr. Negrin University Hospital
Sponsor class: OTHER
Collaborators: name: Li Ka Shing Knowledge Institute
name: Consorcio Centro de Investigación Biomédica en Red (CIBER)
First posted: 2020-03-27
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicenter, randomized, controlled, open-label trial involving mechanically ventilated adult patients with ARDS caused by confirmed COVID-19 infection
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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).

Eligibility criteria: 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.

Primary outcomes:
measure: 60-day mortality
timeFrame: 60 days
Secondary outcomes:
measure: Ventilator-free days
timeFrame: 28 days
Other outcomes:
Locations:
city: Terrassa
country: Spain
facility: ICU, Hospital Universitari Mutua Terrassa
state: Barcelona
city: Las Palmas de Gran Canaria
country: Spain
facility: Hospital Universitario Dr. Negrin
state: Las Palmas
city: Barakaldo
country: Spain
facility: Department of Anesthesia, Hospital Universitario de Cruces
state: Vizcaya
city: Barakaldo
country: Spain
facility: Intensive Care Unit, Hospital Universitario de Cruces
state: Vizcaya
city: Barcelona
country: Spain
facility: AVI, Hospital Clinic
city: Barcelona
country: Spain
facility: Cardiac ICU, Hospital Clinic
city: Barcelona
country: Spain
facility: Department of Anesthesia, Hospital Clinic
city: Barcelona
country: Spain
facility: Hepatic ICU, Hospital Clínic
city: Barcelona
country: Spain
facility: UVIR, Hospital Clinic
city: Ciudad Real
country: Spain
facility: Intensive Care Unit, Hospital General de Ciudad Real
city: Madrid
country: Spain
facility: Department of Anesthesia, Hospital Universitario La Princesa
city: Madrid
country: Spain
facility: Intensive Care Unit, Hospital Universitario La Princesa
city: Madrid
country: Spain
facility: Intensive Care Unit, Hospital Universitario Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Department of Anesthesia, Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Intensive Care Unit, Hospital Universitario La Paz
city: Murcia
country: Spain
facility: Department of Anesthesia, Hospital Universitario Virgen de Arrixaca
city: Murcia
country: Spain
facility: Intensive Care Unit, Hospital Universitario Virgen de la Arrixaca
city: Pontevedra
country: Spain
facility: Department of Anesthesia, Hospital Unversitario Montecelo
city: Valencia
country: Spain
facility: Anesthesia, Hospital General Universitario de Valencia
city: Valencia
country: Spain
facility: Department of Anesthesia, Hospital Clinico Universitario
city: Valencia
country: Spain
facility: Intensive Care Unit, Hospital Clinico Universitario
city: Valladolid
country: Spain
facility: Department of Anesthesia, Hospital Clínico Universitario
city: Valladolid
country: Spain
facility: Anesthesia, Hospital Universitario Río Hortega
city: Valladolid
country: Spain
facility: Intensive Care Unit, Hospital Universitario Río Hortega
Study officials:
affiliation: Hospital Universitario Dr. Negrin
name: Jesús Villar, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Villar J, Belda J, Anon JM, Blanco J, Perez-Mendez L, Ferrando C, Martinez D, Soler JA, Ambros A, Munoz T, Rivas R, Corpas R, Diaz-Dominguez FJ, Soro M, Garcia-Bello MA, Fernandez RL, Kacmarek RM; DEXA-ARDS Network. Evaluating the efficacy of dexamethasone in the treatment of patients with persistent acute respiratory distress syndrome: study protocol for a randomized controlled trial. Trials. 2016 Jul 22;17:342. doi: 10.1186/s13063-016-1456-4.
citation: Villar J, Ferrando C, Martinez D, Ambros A, Munoz T, Soler JA, Aguilar G, Alba F, Gonzalez-Higueras E, Conesa LA, Martin-Rodriguez C, Diaz-Dominguez FJ, Serna-Grande P, Rivas R, Ferreres J, Belda J, Capilla L, Tallet A, Anon JM, Fernandez RL, Gonzalez-Martin JM; dexamethasone in ARDS network. Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial. Lancet Respir Med. 2020 Mar;8(3):267-276. doi: 10.1016/S2213-2600(19)30417-5. Epub 2020 Feb 7.
citation: Villar J, Anon JM, Ferrando C, Aguilar G, Munoz T, Ferreres J, Ambros A, Aldecoa C, Suarez-Sipmann F, Thorpe KE, Juni P, Slutsky AS; DEXA-COVID19 Network. Efficacy of dexamethasone treatment for patients with the acute respiratory distress syndrome caused by COVID-19: study protocol for a randomized controlled superiority trial. Trials. 2020 Aug 16;21(1):717. doi: 10.1186/s13063-020-04643-1.