Acute Respiratory Distress Syndrome Caused by COVID-19Phase 4DEXA-COVID19NCT04325061
Efficacy of Dexamethasone Treatment for Patients With ARDS Caused by COVID-19
A Phase 4 study testing Dexamethasone in people with Acute Respiratory Distress Syndrome Caused by COVID-19, run by Hospital Universitario de Gran Canaria Doctor Negrín at 24 sites in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Respiratory Distress Syndrome Caused by COVID-19
- What is being tested?
- Dexamethasone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 24 sitesSpain
- Study dates
- 3 Apr 2020to 19 Jun 2020
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
24 sites in 1 country.
24 sites in 1 country
Spain24 sites
Department of Anesthesia, Hospital Universitario de Cruces
Barakaldo, Vizcaya, 48903
Intensive Care Unit, Hospital Universitario de Cruces
Barakaldo, Vizcaya, 48903
AVI, Hospital Clinic
Barcelona, 08036
Cardiac ICU, Hospital Clinic
Barcelona, 08036
Department of Anesthesia, Hospital Clinic
Barcelona, 08036
Hepatic ICU, Hospital Clínic
Barcelona, 08036
UVIR, Hospital Clinic
Barcelona, 08036
Intensive Care Unit, Hospital General de Ciudad Real
Ciudad Real, 13005
Hospital Universitario Dr. Negrin
Las Palmas de Gran Canaria, Las Palmas, 35019
Department of Anesthesia, Hospital Universitario La Princesa
Madrid, 28006
Intensive Care Unit, Hospital Universitario La Princesa
Madrid, 28006
Intensive Care Unit, Hospital Universitario Fundación Jiménez Díaz
Madrid, 28040
Department of Anesthesia, Hospital Universitario La Paz
Madrid, 28046
Intensive Care Unit, Hospital Universitario La Paz
Madrid, 28046
Department of Anesthesia, Hospital Universitario Virgen de Arrixaca
Murcia, 30120
Intensive Care Unit, Hospital Universitario Virgen de la Arrixaca
Murcia, 30120
Department of Anesthesia, Hospital Unversitario Montecelo
Pontevedra, 36071
ICU, Hospital Universitari Mutua Terrassa
Terrassa, Barcelona, 08221
Anesthesia, Hospital General Universitario de Valencia
Valencia, 46010
Department of Anesthesia, Hospital Clinico Universitario
Valencia, 46010
Intensive Care Unit, Hospital Clinico Universitario
Valencia, 46010
Department of Anesthesia, Hospital Clínico Universitario
Valladolid, 47003
Anesthesia, Hospital Universitario Río Hortega
Valladolid, 47012
Intensive Care Unit, Hospital Universitario Río Hortega
Valladolid, 47012
About this study
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.
Read the 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).
- Being tested
- Dexamethasone
- Keywords
- ARDS, COVID-19, multiple system organ failure
- Medical subject headings
- COVID-19, Multiple Organ Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexamethasoneDrug
Also called dexamethasone Indukern
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
| Study group | Role | What they receive |
|---|---|---|
| Control group | No intervention | Patients will be treated with standard intensive care |
| Dexamethasone | Active comparator | Standard intensive care plus dexamethasone Receives: Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
60-day mortality
All-cause mortality at 60 days after enrollment
Measured: 60 days
Secondary outcomes (1)
Ventilator-free 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.
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2020
- Study start3 Apr 2020
- Primary completion19 Jun 2020
- Study completion19 Jun 2020
Why it stopped: Lack of enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Acute Respiratory Distress Syndrome Caused by COVID-19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital Universitario de Gran Canaria Doctor Negrín
- Sponsor type
- University, hospital or other
- Collaborators
- Li Ka Shing Knowledge Institute, Consorcio Centro de Investigación Biomédica en Red (CIBER)
- Responsible party
- Principal investigator, Jesus Villar, Hospital Universitario de Gran Canaria Doctor Negrín
- Investigators
- Jesús Villar, MD, Principal investigator, Hospital Universitario Dr. Negrin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04325061
- Sponsor's protocol ID
- 2020-001278-31
- Acronym
- DEXA-COVID19
- Status last verified
- Feb 2021
- First submitted
- 25 Mar 2020
- Last updated
- 3 Feb 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 27449641Villar 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.
PubMed 32043986Villar 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.
PubMed 32799933
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Dexamethasone Treatment for Patients With ARDS Caused by COVID-19
- ClinicalTrials.gov ID
- NCT04325061
- Acronym / sponsor ID
- DEXA-COVID19 / 2020-001278-31
- Keywords
- ARDS, COVID-19, multiple system organ failure
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of enrollment
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Hospital Universitario de Gran Canaria Doctor NegrínUniversity, hospital or other
- Collaborators
- Li Ka Shing Knowledge Institute, Consorcio Centro de Investigación Biomédica en Red (CIBER)
- Study start
- 3 Apr 2020 (actual)
- Primary completion
- 19 Jun 2020 (actual)
- Study completion
- 19 Jun 2020 (actual)
- First posted
- 27 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Multicenter, randomized, controlled, open-label trial involving mechanically ventilated adult patients with ARDS caused by confirmed COVID-19 infection
| Arm | Type | Receives |
|---|---|---|
| Control group | No intervention | –Patients will be treated with standard intensive care |
| Dexamethasone | Active comparator | Drug: DexamethasoneStandard intensive care plus dexamethasone |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (6 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DexamethasoneAlso: dexamethasone IndukernDexamethasone (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 | Drug | Dexamethasone |
Primary outcome
60-day mortality
Time frame: 60 days
All-cause mortality at 60 days after enrollment
1 secondary outcome
Ventilator-free days
Time frame: 28 days
Results and safety
The study was stopped early (reason given: Lack of enrollment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2021.
- Results publication: PubMed 27449641Villar 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.
- Results publication: PubMed 32043986Villar 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.
- Derived from this study: PubMed 32799933Villar 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jesús Villar, MD principal investigator
Hospital Universitario Dr. Negrin
24 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Dexamethasone in people with Acute Respiratory Distress Syndrome Caused by COVID-19, run by Hospital Universitario de Gran Canaria Doctor Negrín at 24 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 3 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Lack of enrollment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
60-day mortality (time frame: 60 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04325061, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Feb 2021.