COVID-19Phase 3EARLYDEXCoV2NCT04836780
DEXamethasone EARLY Administration in Hospitalized Patients With Covid-19 Pneumonia
A Phase 3 study testing Dexamethasone in people with COVID-19 and Acute Respiratory Distress Syndrome, run by Hospital Universitario Infanta Leonor at 3 sites in Spain.
Trial summary
The aim of this study is to evaluate the efficacy of dexamethasone in hospitalized adults with COVID-19 pneumonia who do not require supplementary oxygen on admission, but have high risk of developing acute respiratory distress syndrome (ARDS). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19, Acute Respiratory Distress Syndrome, Pneumonia, Viral
- 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
- 126 participants
- Where
- 3 sitesSpain
- Study dates
- 10 Jun 2021to 30 Mar 2023
- Phase
- Phase 3
- 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
- Adults (age 18 years or older).
- Diagnosed with SARS-CoV-2 infection by Polymerase Chain Reaction or rapid antigen test on upper respiratory tract (nasopharyngeal and oropharyngeal) specimens.
- Evidence of infiltrates on chest radiography or computerized tomography.
- Peripheral capillary oxygen saturation (SpO2) ≥94% and <22 breaths per minute (bpm) breathing room air.
- High risk of developing ARDS defined by a lactate dehydrogenase higher than 245 U/L, C-Reactive Protein higher than 100 mg/L, and absolute lymphocytes lower than 800 cells/µL. Eligible participants will meet two of the three before analytical criteria associated with severe COVID-19.
- Patients will provide written informed consent or who have a legally authorized representative available to do so. In these exceptional circumstances and following the recommendations of the Spanish Agency of Medicines and Medical Devices, the National Competent Authority of clinical trials, during the coronavirus crisis to avoid the risk of contagion, consent will be possible to obtained orally in the presence of at least one impartial witness.
Who cannot join
- Patients with a history of allergy to dexamethasone.
- Pregnant or lactating women.
- Oral or inhaled corticosteroids treatment within 15 days before randomization.
- Immunosuppressive agent or cytotoxic drug therapy within 30 days before randomization.
- Neutropenia <1000 cells/µL.
- Human immunodeficiency virus infection with CD4 cell counts <500 cells within 90 days after randomization.
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- Dementia.
- Chronic liver disease defined by ALT or AST ≥5 times the upper limit of normal.
- Chronic kidney injury defined by a glomerular filtration rate ≤30 ml/min, hemodialysis or peritoneal dialysis.
- Uncontrolled infection.
- Patients who are already enrolled in another clinical trial.
Trial locations and contacts
3 sites in 1 country.
Spain3 sites, 3 recruiting
- Recruiting
Hospital Universitario Infanta Leonor
Madrid, 28031
Anabel Franco Moreno, MD, PhD, +34 911 91 80 00, afranco278@hotmail.com
Anabel Franco Moreno, MD, PhD
- Recruiting
Hospital Universitario Clínico San Carlos
Madrid, 28040
Noemí Cabello Clotet, MD, +34 913 30 30 00, cabelloclotetn@gmail.com
Noemí Cabello Clotet, MD
- Recruiting
Hospital Emergencias Enfermera Isabel Zendal
Madrid, 28055
David Alonso Menchen, MD, +34 917 99 63 00, david.alonso@salud.madrid.org
David Alonso Menchen, MD, +34 917 9 63 00, david.alonso@salud.madrid.org
About this study
Official title: DEXamethasone EARLY Administration in Hospitalized Patients With Covid-19 Pneumonia and High Risk of Developing Acute Respiratory Distress Syndrome
The aim of this study is to evaluate the efficacy of dexamethasone in hospitalized adults with COVID-19 pneumonia who do not require supplementary oxygen on admission, but have high risk of developing acute respiratory distress syndrome (ARDS).
This is a prospective, multicenter, phase 4, parallel-group, randomized and controlled trial that is open-label to investigators, participants and clinical outcome assessors.
Read more
Eligible participants include adults (age 18 years or older), diagnosed with SARS-CoV-2 infection, evidence of infiltrates on chest radiography or computerized tomography, peripheral capillary oxygen saturation ≥94% and 22 breaths per minute breathing room air, and high risk of developing ARDS defined by a lactate dehydrogenase higher than 245 U/L, C-Reactive Protein higher than 100 mg/L, and absolute lymphocytes lower than 800 cells/µL. Eligible participants will meet two of the three before analytical criteria associated with severe COVID-19. Patients will provide written informed consent. Exclusion criteria include patients with a history of allergy to dexamethasone, pregnant or lactating women, oral or inhaled corticosteroids treatment within 15 days before randomization, immunosuppressive agent or cytotoxic drug therapy within 30 days before randomization, neutropenia <1000 cells/µL, human immunodeficiency virus infection with CD4 cell counts <500 cells within 90 days after randomization, dementia, chronic liver disease defined by ALT or AST ≥5 times the upper limit of normal, chronic kidney injury defined by a glomerular filtration rate ≤30 ml/min, hemodialysis or peritoneal dialysis, uncontrolled infection, and patients who are already enrolled in another clinical trial.
Study participants will be randomized in a 1:1 ratio to receive dexamethasone base 6 mg once daily for seven days or standard of care.
The primary endpoint is to prevent of development of moderate ARDS. Based on the Berlin criteria, moderate ARDS is defined by a PaO2/FiO2 ratio >100 mmHg and ≤200 mmHg.
Study participants will be randomized in a 1:1 ratio to receive dexamethasone versus standard of care using a randomization platform. Included participants will be hospitalized at the time of randomization.
The study will be undertaken at Infanta Leonor-Virgen de la Torre University Hospital, Enfermera Isabel Zendal Emergency Hospital, and Infanta Cristina Hospital, Madrid, Spain.
Read the detailed description
Coronavirus disease 2019 (COVID-19) can lead to acute respiratory distress syndrome (ARDS), severe hypoxic respiratory failure and, death. It has been reported that the mechanism of COVID-19 is related to cytokine storms and subsequent immunogenic damage, especially lung damage. Dexamethasone, with immunomodulatory properties, decrease mortality in critically ill patients with COVID-19. However, the benefits in patients without hypoxia remain unknown. We hypothesize that early administration of dexamethasone in hospitalized adult patients with COVID-19 pneumonia without hypoxia on admission, but risk factors for developing ARDS might prevent severe acute respiratory failure and death.
The investigators designed a multicenter prospective phase 3 parallel-group randomized and controlled trial. It is planned to recruit 126 hospitalized adults patients with COVID-19 pneumonia without hypoxia on admission, but at high risk of developing ARDS, admitted to the emergency room or internal medicine wards. One enrolled, the participants will be randomised to receive oral or intravenous dexamethasone base at a dose of 6 mg once daily for 7 days or standard of care once enrolled. The primary outcome is the development of moderate-severe ARDS in patients with COVID-19 pneumonia without hypoxia on admission, but at high risk of disease progression. Based on the Berlin criteria, moderate ARDS is defined by a PaO2/FiO2 ratio >100 mmHg and ≤200 mmHg. According to The American College of Chest Physicians patients with a PaO2/FiO2 ratio around 200 mmHg requiring supplemental oxygen in nasal cannula at 3 L/min (FiO2 0.30) for a SpO2 of 91-92%. Safety data will be provided. The secondary endpoints are: All-cause mortality for 28 days after randomization, intensive Care Unit (ICU) or Intermediate Respiratory Care Unit (IRCU) transfer for 28 days after randomization, clinical status of the patient using the ordinal scale of the WHO, SOFA on admission, and 4 and 7 days after randomization, hospital length of stay, respiratory support at hospital discharge, and all-cause readmission rate for 3 months after randomization.
This trial is considered to be safe. First, dexamethasone has been widely used in clinical practice for decades, and second, patients with greater potential risks of side effects were excluded based on the exclusion criteria. However, adverse events (AE) and serious adverse events (SAE) must be observed and followed in accordance with the good clinical practice guidelines issued by the European Medicine Agency (EMA).AE and SAE will be recorded for 7 days of observation from enrolment. Either may occur during a subject's participation in the research and do not need to have a causal relationship with the treatment. Investigators will evaluate the relationship between the events and the intervention and report it to the ethics committee and data and safety monitoring board. Benefits and potential risks are written in the informed consent document. Patients will be informed about the purpose, interventions, benefits and possible risks of the study.
Baseline data including demographic characteristics, assigned group, Sequential Organs Failure Assessment (SOFA) score, the clinical status of the patient using the ordinal scale of the WHO, SpO2, partial pressure of arterial oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio calculated from SpO2/FiO2, blood routine tests, chest radiography, and concomitant drugs will be collected on the first day. General vital signs, changes in the SOFA score, changes in the ordinal scale of the WHO, SpO2, respiratory rate, PaO2/FiO2 ratio, respiratory support, chest radiography, concomitant drugs, adverse event monitoring will be collected on the first day, fourth, seventh, fourteenth day and at discharge. Participants are scheduled for a follow-up visit on the 30 and 90th day to track their long-term prognosis, clinical status and sequelae.
Data will be collected from the clinical information system of the hospital. Every participant will be distinguished with a study identifier and initial without full name. An electronic password-protected document containing all the information from the case report format will be set up for statistical analysis. The analysis process will be performed by the primary investigator and designated teammates who are experienced with the trial case report format. The confidentiality and safety of participant's data are guaranteed. Data will be reserved for 25 years for further analysis and investigation in accordance with the European Clinical Trials Directive.
We assumed that 30% of participants would meet ARDS, and the use of dexamethasone would reduce this percentage to 15%. This corresponds to a required sample size of 63 per arm, with a 5% two-sided significance level (alpha) and 80% power. The total sample size therefore is planned to be 126. Quantitative variables will be described as the mean with standard deviation when they had a normal distribution, or median and interquartile range (IQR) when they had a non-normal distribution. Qualitative variables were defined by the frequency distribution and percentages. For univariate analysis, the difference in measurement data will be compared between the dexamethasone and standard care groups using Student's t -test or the Mann-Whitney U, and qualitative variables will be compared using Chi-squared test and Fisher's exact test depending on the normality of the variable. Kaplan-Meier analysis will be used to show the effect of dexamethasone on patient survival probability. A p-value of less than 0.05 will be considered statistically significant. Results will be obtained using Statistical Package for the Social Sciences software, version 26.0.
Results will be submitted for publication in peer-reviewed journals.
- Being tested
- Dexamethasone
- Keywords
- COVID-19 pneumonia, Acute respiratory distress syndrome, Prevention, Randomised controlled trial, Dexamethasone
- Medical subject headings
- COVID-19, Respiratory Distress Syndrome, Pneumonia, Viral
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexamethasoneDrug
Also called Dexametasona kern pharma solution for injection 4 mg/ml
Dexamethasone base 6 mg once daily for seven days
| Study group | Role | What they receive |
|---|---|---|
| Dexamethasone | Experimental | Dexamethasone base 6 mg once daily for seven days Receives: Drug: Dexamethasone |
| Standard of care | Active comparator | Standard care therapy Receives: Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary trial outcome is the development of moderate-severe ARDS
Based on the Berlin criteria, moderate ARDS is defined by a PaO2/FiO2 ratio >100 mmHg and ≤200 mmHg. According to The American College of Chest Physicians patients with a PaO2/FiO2 ratio around 200 mmHg requiring supplemental oxygen in nasal cannula at 3 L/min (FiO2 0.30) for a SpO2 of 91-92%. The collected data as outcome measure will be general vital sign, Sequential Organ Failure Assessment (SOFA) score, the clinical status of the patient using the ordinal scale of the WHO, SpO2, partial pressure of arterial oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio calculated from SpO2/FiO2, blood routine tests and chest radiography. Concomitant drugs and adverse event monitoring will be collected. Data will measure during admission. Participants will schedule for a follow-up visit on the 30 and 90th day to track their long-term prognosis, clinical status and sequelae.
Measured: 7 days
Secondary outcomes (7)
All-cause mortality for 28 days after randomization
All-cause mortality for 28 days after randomization
Measured: 28 days
Intensive Care Unit (ICU) or Intermediate Respiratory Care Unit (IRCU) transfer for 28 days after randomization
Intensive Care Unit (ICU) or Intermediate Respiratory Care Unit (IRCU) transfer for 28 days after randomization
Measured: 28 days
Clinical status of the patient using the ordinal scale of the WHO
The World Health Organization COVID-19 ordinal scale represents intensity of medical intervention, with higher scores for interventions more burdensome for the patient, and highest score for death. Minimum value = 1, and maximum value = 8
Measured: 7 days
Sequential Organ Failure Assessment (SOFA) score on admission, and 4 and 7 days after randomization
The Sequential Organ Failure Assessment score is a simple and objective score that allows for calculation of both the number and the severity of organ dysfunction in six organ systems (respiratory, coagulatory, liver, cardiovascular, renal, and neurologic). The SOFA score can be used to determine level of organ dysfunction and mortality risk. Higher scores for interventions more burdensome for the patient, and highest score for death. Minimum value = 0, and maximum value = 24
Measured: 7 days
Hospital length of stay
Hospital length of stay in days. From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 90 days.
Measured: Number of days between admission date and discharge
Respiratory support at hospital discharge
Suplementary oxygen at hospital discharge up to 90 days
Measured: At hospital discharge
All-cause readmission rate for 3 months after randomization
All-cause readmission rate for 3 months after randomization
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2021
- Study start10 Jun 2021
- Primary completion28 Feb 2023 (estimated)
- Study completion30 Mar 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for 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 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a prospective, multicentre, phase 3, parallel-group, randomized and controlled trial that is open-label to investigators, participants and clinical outcome assessors
- Masking
- None (open label)
- Enrolment
- 126 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospital Universitario Infanta Leonor
- Sponsor type
- University, hospital or other
- Collaborators
- Fundación para la Investigación e Innovación Biomédica del Hospital Universitario Infanta Leonor, Kern Pharma, S.L.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04836780
- Sponsor's protocol ID
- EARLY-DEX Covid-19
- Acronym
- EARLYDEXCoV2
- Status last verified
- Jan 2023
- First submitted
- 18 Mar 2021
- Last updated
- 1 Mar 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, Wu Y, Zhang L, Yu Z, Fang M, Yu T, Wang Y, Pan S, Zou X, Yuan S, Shang Y. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020 May;8(5):475-481. doi: 10.1016/S2213-2600(20)30079-5. Epub 2020 Feb 24.
PubMed 32105632Siddiqi HK, Mehra MR. COVID-19 illness in native and immunosuppressed states: A clinical-therapeutic staging proposal. J Heart Lung Transplant. 2020 May;39(5):405-407. doi: 10.1016/j.healun.2020.03.012. Epub 2020 Mar 20. No abstract available.
PubMed 32362390Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H, Wang T, Zhang X, Chen H, Yu H, Zhang X, Zhang M, Wu S, Song J, Chen T, Han M, Li S, Luo X, Zhao J, Ning Q. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 2020 May 1;130(5):2620-2629. doi: 10.1172/JCI137244.
PubMed 32217835RECOVERY Collaborative Group; Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, Staplin N, Brightling C, Ustianowski A, Elmahi E, Prudon B, Green C, Felton T, Chadwick D, Rege K, Fegan C, Chappell LC, Faust SN, Jaki T, Jeffery K, Montgomery A, Rowan K, Juszczak E, Baillie JK, Haynes R, Landray MJ. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021 Feb 25;384(8):693-704. doi: 10.1056/NEJMoa2021436. Epub 2020 Jul 17.
PubMed 32678530WHO/2019-nCoV/Corticosteroids/2020.1
Baud D, Qi X, Nielsen-Saines K, Musso D, Pomar L, Favre G. Real estimates of mortality following COVID-19 infection. Lancet Infect Dis. 2020 Jul;20(7):773. doi: 10.1016/S1473-3099(20)30195-X. Epub 2020 Mar 12. No abstract available.
PubMed 32171390Monedero P, Gea A, Castro P, Candela-Toha AM, Hernandez-Sanz ML, Arruti E, Villar J, Ferrando C; COVID-19 Spanish ICU Network. Early corticosteroids are associated with lower mortality in critically ill patients with COVID-19: a cohort study. Crit Care. 2021 Jan 4;25(1):2. doi: 10.1186/s13054-020-03422-3.
PubMed 33397463Fadel R, Morrison AR, Vahia A, Smith ZR, Chaudhry Z, Bhargava P, Miller J, Kenney RM, Alangaden G, Ramesh MS; Henry Ford COVID-19 Management Task Force. Early Short-Course Corticosteroids in Hospitalized Patients With COVID-19. Clin Infect Dis. 2020 Nov 19;71(16):2114-2120. doi: 10.1093/cid/ciaa601.
PubMed 32427279Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062. doi: 10.1016/S0140-6736(20)30566-3. Epub 2020 Mar 11.
PubMed 32171076Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020 May;46(5):846-848. doi: 10.1007/s00134-020-05991-x. Epub 2020 Mar 3. No abstract available.
PubMed 32125452Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24.
PubMed 31986264Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, Du B, Li LJ, Zeng G, Yuen KY, Chen RC, Tang CL, Wang T, Chen PY, Xiang J, Li SY, Wang JL, Liang ZJ, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ, Qiu SQ, Luo J, Ye CJ, Zhu SY, Zhong NS; China Medical Treatment Expert Group for Covid-19. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Apr 30;382(18):1708-1720. doi: 10.1056/NEJMoa2002032. Epub 2020 Feb 28.
PubMed 32109013Franco-Moreno A, Acedo-Gutierrez MS, Casado-Suela MA, Labrador-San Martin N, de Carranza-Lopez M, Ibanez-Estellez F, Hernandez-Blanco C, Jimenez-Torres J, Vallejo-Maroto I, Romero-Pareja R, Pena-Lillo G, Escobar-Rodriguez I, Torres-Macho J; EARLY-DEX COVID-19 Research Group. Effect of early administration of dexamethasone in patients with COVID-19 pneumonia without acute hypoxemic respiratory failure and risk of development of acute respiratory distress syndrome: EARLY-DEX COVID-19 trial. Front Med (Lausanne). 2024 Jul 17;11:1385833. doi: 10.3389/fmed.2024.1385833. eCollection 2024.
PubMed 39086948Franco-Moreno A, Acedo-Gutierrez MS, Martin NL, Hernandez-Blanco C, Rodriguez-Olleros C, Ibanez-Estellez F, Suarez-Simon A, Balado-Rico M, Romero-Paternina AR, Alonso-Menchen D, Escolano-Fernandez B, Piniella-Ruiz E, Alonso-Monge E, Notario-Leo H, Bibiano-Guillen C, Pena-Lillo G, Antiqueira-Perez A, Romero-Pareja R, Cabello-Clotet N, Estrada-Perez V, Troya-Garcia J, de Carranza-Lopez M, Escobar-Rodriguez I, Vallejo-Maroto N, Torres-Macho J. Effect of EARLY administration of DEXamethasone in patients with COVID-19 pneumonia without acute hypoxemic respiratory failure and risk of development of acute respiratory distress syndrome (EARLY-DEX COVID-19): study protocol for a randomized controlled trial. Trials. 2022 Sep 15;23(1):784. doi: 10.1186/s13063-022-06722-x.
PubMed 36109825
Study at a glance
From the registry record, last updated by the sponsor on 1 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- DEXamethasone EARLY Administration in Hospitalized Patients With Covid-19 Pneumonia and High Risk of Developing Acute Respiratory Distress Syndrome
- ClinicalTrials.gov ID
- NCT04836780
- Acronym / sponsor ID
- EARLYDEXCoV2 / EARLY-DEX Covid-19
- Keywords
- COVID-19 pneumonia, Acute respiratory distress syndrome, Prevention, Randomised controlled trial, Dexamethasone
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 126 participants (estimated)
- Lead sponsor
- Hospital Universitario Infanta LeonorUniversity, hospital or other
- Collaborators
- Fundación para la Investigación e Innovación Biomédica del Hospital Universitario Infanta Leonor, Kern Pharma, S.L.
- Study start
- 10 Jun 2021 (actual)
- Primary completion
- 28 Feb 2023 (estimated)
- Study completion
- 30 Mar 2023 (estimated)
- First posted
- 8 Apr 2021 (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.
The aim of this study is to evaluate the efficacy of dexamethasone in hospitalized adults with COVID-19 pneumonia who do not require supplementary oxygen on admission, but have high risk of developing acute respiratory distress syndrome (ARDS).
This is a prospective, multicenter, phase 4, parallel-group, randomized and controlled trial that is open-label to investigators, participants and clinical outcome assessors.
Eligible participants include adults (age 18 years or older), diagnosed with SARS-CoV-2 infection, evidence of infiltrates on chest radiography or computerized tomography, peripheral capillary oxygen saturation ≥94% and 22 breaths per minute breathing room air, and high risk of developing ARDS defined by a lactate dehydrogenase higher than 245 U/L, C-Reactive Protein higher than 100 mg/L, and absolute lymphocytes lower than 800 cells/µL. Eligible participants will meet two of the three before analytical criteria associated with severe COVID-19. Patients will provide written informed consent. Exclusion criteria include patients with a history of allergy to dexamethasone, pregnant or lactating women, oral or inhaled corticosteroids treatment within 15 days before randomization, immunosuppressive agent or cytotoxic drug therapy within 30 days before randomization, neutropenia <1000 cells/µL, human immunodeficiency virus infection with CD4 cell counts <500 cells within 90 days after randomization, dementia, chronic liver disease defined by ALT or AST ≥5 times the upper limit of normal, chronic kidney injury defined by a glomerular filtration rate ≤30 ml/min, hemodialysis or peritoneal dialysis, uncontrolled infection, and patients who are already enrolled in another clinical trial.
Study participants will be randomized in a 1:1 ratio to receive dexamethasone base 6 mg once daily for seven days or standard of care.
The primary endpoint is to prevent of development of moderate ARDS. Based on the Berlin criteria, moderate ARDS is defined by a PaO2/FiO2 ratio >100 mmHg and ≤200 mmHg.
Study participants will be randomized in a 1:1 ratio to receive dexamethasone versus standard of care using a randomization platform. Included participants will be hospitalized at the time of randomization.
The study will be undertaken at Infanta Leonor-Virgen de la Torre University Hospital, Enfermera Isabel Zendal Emergency Hospital, and Infanta Cristina Hospital, Madrid, Spain.
Detailed description
Coronavirus disease 2019 (COVID-19) can lead to acute respiratory distress syndrome (ARDS), severe hypoxic respiratory failure and, death. It has been reported that the mechanism of COVID-19 is related to cytokine storms and subsequent immunogenic damage, especially lung damage. Dexamethasone, with immunomodulatory properties, decrease mortality in critically ill patients with COVID-19. However, the benefits in patients without hypoxia remain unknown. We hypothesize that early administration of dexamethasone in hospitalized adult patients with COVID-19 pneumonia without hypoxia on admission, but risk factors for developing ARDS might prevent severe acute respiratory failure and death.
The investigators designed a multicenter prospective phase 3 parallel-group randomized and controlled trial. It is planned to recruit 126 hospitalized adults patients with COVID-19 pneumonia without hypoxia on admission, but at high risk of developing ARDS, admitted to the emergency room or internal medicine wards. One enrolled, the participants will be randomised to receive oral or intravenous dexamethasone base at a dose of 6 mg once daily for 7 days or standard of care once enrolled. The primary outcome is the development of moderate-severe ARDS in patients with COVID-19 pneumonia without hypoxia on admission, but at high risk of disease progression. Based on the Berlin criteria, moderate ARDS is defined by a PaO2/FiO2 ratio >100 mmHg and ≤200 mmHg. According to The American College of Chest Physicians patients with a PaO2/FiO2 ratio around 200 mmHg requiring supplemental oxygen in nasal cannula at 3 L/min (FiO2 0.30) for a SpO2 of 91-92%. Safety data will be provided. The secondary endpoints are: All-cause mortality for 28 days after randomization, intensive Care Unit (ICU) or Intermediate Respiratory Care Unit (IRCU) transfer for 28 days after randomization, clinical status of the patient using the ordinal scale of the WHO, SOFA on admission, and 4 and 7 days after randomization, hospital length of stay, respiratory support at hospital discharge, and all-cause readmission rate for 3 months after randomization.
This trial is considered to be safe. First, dexamethasone has been widely used in clinical practice for decades, and second, patients with greater potential risks of side effects were excluded based on the exclusion criteria. However, adverse events (AE) and serious adverse events (SAE) must be observed and followed in accordance with the good clinical practice guidelines issued by the European Medicine Agency (EMA).AE and SAE will be recorded for 7 days of observation from enrolment. Either may occur during a subject's participation in the research and do not need to have a causal relationship with the treatment. Investigators will evaluate the relationship between the events and the intervention and report it to the ethics committee and data and safety monitoring board. Benefits and potential risks are written in the informed consent document. Patients will be informed about the purpose, interventions, benefits and possible risks of the study.
Baseline data including demographic characteristics, assigned group, Sequential Organs Failure Assessment (SOFA) score, the clinical status of the patient using the ordinal scale of the WHO, SpO2, partial pressure of arterial oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio calculated from SpO2/FiO2, blood routine tests, chest radiography, and concomitant drugs will be collected on the first day. General vital signs, changes in the SOFA score, changes in the ordinal scale of the WHO, SpO2, respiratory rate, PaO2/FiO2 ratio, respiratory support, chest radiography, concomitant drugs, adverse event monitoring will be collected on the first day, fourth, seventh, fourteenth day and at discharge. Participants are scheduled for a follow-up visit on the 30 and 90th day to track their long-term prognosis, clinical status and sequelae.
Data will be collected from the clinical information system of the hospital. Every participant will be distinguished with a study identifier and initial without full name. An electronic password-protected document containing all the information from the case report format will be set up for statistical analysis. The analysis process will be performed by the primary investigator and designated teammates who are experienced with the trial case report format. The confidentiality and safety of participant's data are guaranteed. Data will be reserved for 25 years for further analysis and investigation in accordance with the European Clinical Trials Directive.
We assumed that 30% of participants would meet ARDS, and the use of dexamethasone would reduce this percentage to 15%. This corresponds to a required sample size of 63 per arm, with a 5% two-sided significance level (alpha) and 80% power. The total sample size therefore is planned to be 126. Quantitative variables will be described as the mean with standard deviation when they had a normal distribution, or median and interquartile range (IQR) when they had a non-normal distribution. Qualitative variables were defined by the frequency distribution and percentages. For univariate analysis, the difference in measurement data will be compared between the dexamethasone and standard care groups using Student's t -test or the Mann-Whitney U, and qualitative variables will be compared using Chi-squared test and Fisher's exact test depending on the normality of the variable. Kaplan-Meier analysis will be used to show the effect of dexamethasone on patient survival probability. A p-value of less than 0.05 will be considered statistically significant. Results will be obtained using Statistical Package for the Social Sciences software, version 26.0.
Results will be submitted for publication in peer-reviewed journals.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This is a prospective, multicentre, phase 3, parallel-group, randomized and controlled trial that is open-label to investigators, participants and clinical outcome assessors
| Arm | Type | Receives |
|---|---|---|
| Dexamethasone | Experimental | Drug: DexamethasoneDexamethasone base 6 mg once daily for seven days |
| Standard of care | Active comparator | Drug: DexamethasoneStandard care therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Adults (age 18 years or older).
- Diagnosed with SARS-CoV-2 infection by Polymerase Chain Reaction or rapid antigen test on upper respiratory tract (nasopharyngeal and oropharyngeal) specimens.
- Evidence of infiltrates on chest radiography or computerized tomography.
- Peripheral capillary oxygen saturation (SpO2) ≥94% and <22 breaths per minute (bpm) breathing room air.
- High risk of developing ARDS defined by a lactate dehydrogenase higher than 245 U/L, C-Reactive Protein higher than 100 mg/L, and absolute lymphocytes lower than 800 cells/µL. Eligible participants will meet two of the three before analytical criteria associated with severe COVID-19.
Key exclusion criteria (11 listed)
- Patients with a history of allergy to dexamethasone.
- Pregnant or lactating women.
- Oral or inhaled corticosteroids treatment within 15 days before randomization.
- Immunosuppressive agent or cytotoxic drug therapy within 30 days before randomization.
- Neutropenia <1000 cells/µL.
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: Dexametasona kern pharma solution for injection 4 mg/mlDexamethasone base 6 mg once daily for seven days | Drug | Dexamethasone, Standard of care |
Primary outcome
The primary trial outcome is the development of moderate-severe ARDS
Time frame: 7 days
Based on the Berlin criteria, moderate ARDS is defined by a PaO2/FiO2 ratio >100 mmHg and ≤200 mmHg. According to The American College of Chest Physicians patients with a PaO2/FiO2 ratio around 200 mmHg requiring supplemental oxygen in nasal cannula at 3 L/min (FiO2 0.30) for a SpO2 of 91-92%. The collected data as outcome measure will be general vital sign, Sequential Organ Failure Assessment (SOFA) score, the clinical status of the patient using the ordinal scale of the WHO, SpO2, partial pressure of arterial oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio calculated from SpO2/FiO2, blood routine tests and chest radiography. Concomitant drugs and adverse event monitoring will be collected. Data will measure during admission. Participants will schedule for a follow-up visit on the 30 and 90th day to track their long-term prognosis, clinical status and sequelae.
7 secondary outcomes
All-cause mortality for 28 days after randomization
Time frame: 28 days
Intensive Care Unit (ICU) or Intermediate Respiratory Care Unit (IRCU) transfer for 28 days after randomization
Time frame: 28 days
Clinical status of the patient using the ordinal scale of the WHO
Time frame: 7 days
Sequential Organ Failure Assessment (SOFA) score on admission, and 4 and 7 days after randomization
Time frame: 7 days
Hospital length of stay
Time frame: Number of days between admission date and discharge
Respiratory support at hospital discharge
Time frame: At hospital discharge
All-cause readmission rate for 3 months after randomization
Time frame: 3 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Mar 2023.
- Results publication: PubMed 32105632Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, Wu Y, Zhang L, Yu Z, Fang M, Yu T, Wang Y, Pan S, Zou X, Yuan S, Shang Y. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020 May;8(5):475-481. doi: 10.1016/S2213-2600(20)30079-5. Epub 2020 Feb 24.
- Results publication: PubMed 32362390Siddiqi HK, Mehra MR. COVID-19 illness in native and immunosuppressed states: A clinical-therapeutic staging proposal. J Heart Lung Transplant. 2020 May;39(5):405-407. doi: 10.1016/j.healun.2020.03.012. Epub 2020 Mar 20. No abstract available.
- Results publication: PubMed 32217835Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H, Wang T, Zhang X, Chen H, Yu H, Zhang X, Zhang M, Wu S, Song J, Chen T, Han M, Li S, Luo X, Zhao J, Ning Q. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 2020 May 1;130(5):2620-2629. doi: 10.1172/JCI137244.
- Results publication: PubMed 32678530RECOVERY Collaborative Group; Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, Staplin N, Brightling C, Ustianowski A, Elmahi E, Prudon B, Green C, Felton T, Chadwick D, Rege K, Fegan C, Chappell LC, Faust SN, Jaki T, Jeffery K, Montgomery A, Rowan K, Juszczak E, Baillie JK, Haynes R, Landray MJ. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021 Feb 25;384(8):693-704. doi: 10.1056/NEJMoa2021436. Epub 2020 Jul 17.
- Results publicationWHO/2019-nCoV/Corticosteroids/2020.1
- Results publication: PubMed 32171390Baud D, Qi X, Nielsen-Saines K, Musso D, Pomar L, Favre G. Real estimates of mortality following COVID-19 infection. Lancet Infect Dis. 2020 Jul;20(7):773. doi: 10.1016/S1473-3099(20)30195-X. Epub 2020 Mar 12. No abstract available.
- Results publication: PubMed 33397463Monedero P, Gea A, Castro P, Candela-Toha AM, Hernandez-Sanz ML, Arruti E, Villar J, Ferrando C; COVID-19 Spanish ICU Network. Early corticosteroids are associated with lower mortality in critically ill patients with COVID-19: a cohort study. Crit Care. 2021 Jan 4;25(1):2. doi: 10.1186/s13054-020-03422-3.
- Results publication: PubMed 32427279Fadel R, Morrison AR, Vahia A, Smith ZR, Chaudhry Z, Bhargava P, Miller J, Kenney RM, Alangaden G, Ramesh MS; Henry Ford COVID-19 Management Task Force. Early Short-Course Corticosteroids in Hospitalized Patients With COVID-19. Clin Infect Dis. 2020 Nov 19;71(16):2114-2120. doi: 10.1093/cid/ciaa601.
- Results publication: PubMed 32171076Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062. doi: 10.1016/S0140-6736(20)30566-3. Epub 2020 Mar 11.
- Results publication: PubMed 32125452Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020 May;46(5):846-848. doi: 10.1007/s00134-020-05991-x. Epub 2020 Mar 3. No abstract available.
- Results publication: PubMed 31986264Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24.
- Results publication: PubMed 32109013Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, Du B, Li LJ, Zeng G, Yuen KY, Chen RC, Tang CL, Wang T, Chen PY, Xiang J, Li SY, Wang JL, Liang ZJ, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ, Qiu SQ, Luo J, Ye CJ, Zhu SY, Zhong NS; China Medical Treatment Expert Group for Covid-19. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Apr 30;382(18):1708-1720. doi: 10.1056/NEJMoa2002032. Epub 2020 Feb 28.
- 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.
Hospital Emergencias Enfermera Isabel Zendal
Madrid, Spain
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Dexamethasone in people with COVID-19 and Acute Respiratory Distress Syndrome, run by Hospital Universitario Infanta Leonor at 3 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 6 inclusion and 11 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: status not confirmed, as of the sponsor's last update on 1 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary trial outcome is the development of moderate-severe ARDS (time frame: 7 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 NCT04836780, which also lists 14 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 1 Mar 2023.