Efficacy of Dexamethasone Treatment for Patients With ARDS Caused by COVID-19 (DEXA-COVID19)

• ClinicalTrials.gov Identifier: NCT04325061
• Recruitment Status: Terminated
• First Posted: March 27, 2020
• Last Update Posted: February 3, 2021
• Sponsor: Dr. Negrin University Hospital
• Collaborators: Li Ka Shing Knowledge Institute; Consorcio Centro de Investigación Biomédica en Red, M.P.
• Information provided by (Responsible Party): Jesus Villar, Dr. Negrin University Hospital

Tracking Information

• First Submitted Date: March 25, 2020
• First Posted Date: March 27, 2020
• Last Update Posted Date: February 3, 2021
• Actual Study Start Date: April 3, 2020
• Actual Primary Completion Date: June 19, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 29, 2020)

60-day mortality [ Time Frame: 60 days ]

All-cause mortality at 60 days after enrollment

Original Primary Outcome Measures (submitted: March 26, 2020)

60-day mortality [ Time Frame: 60 days ]

All-cause mortality at 60 days after after enrollment

Current Secondary Outcome Measures (submitted: March 26, 2020)

Ventilator-free days [ Time Frame: 28 days ]

Number of ventilator-free days (VFDs) at Day 28 (defined as days being alive and free from mechanical ventilation at day 28 after enrollment, For patients ventilated 28 days or longer and for subjects who die, VFD is 0.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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).

• Study Type: Interventional
• Study Phase: Phase 4

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Multicenter, randomized, controlled, open-label trial involving mechanically ventilated adult patients with ARDS caused by confirmed COVID-19 infection

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Acute Respiratory Distress Syndrome Caused by COVID-19

Intervention

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

Study Arms

• No Intervention: Control group
  Patients will be treated with standard intensive care
• Active Comparator: Dexamethasone
  Standard intensive care plus dexamethasone
  Intervention: Drug: Dexamethasone

Publications *

• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: February 2, 2021): 19
• Original Estimated Enrollment (submitted: March 26, 2020): 200
• Actual Study Completion Date: June 19, 2020
• Actual Primary Completion Date: June 19, 2020 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Spain

Administrative Information

• NCT Number: NCT04325061
• Other Study ID Numbers: 2020-001278-31
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Jesus Villar, Dr. Negrin University Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Dr. Negrin University Hospital
• Original Study Sponsor: Same as current

Collaborators

• Li Ka Shing Knowledge Institute
• Consorcio Centro de Investigación Biomédica en Red, M.P.

Investigators

• Principal Investigator: Jesús Villar, MD; Hospital Universitario Dr. Negrin

• PRS Account: Dr. Negrin University Hospital
• Verification Date: February 2021