DEXamethasone EARLY Administration in Hospitalized Patients With Covid-19 Pneumonia

NCT04836780 | Unknown Phase 3 DMC

• 1 other identifier: EARLY-DEX Covid-19
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 3

Brief 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). 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.

Conditions

COVID-19; Acute Respiratory Distress Syndrome; Pneumonia, Viral

Keywords

COVID-19 pneumonia; Acute respiratory distress syndrome; Prevention; Randomised controlled trial; Dexamethasone

Outcome Measures

Primary Outcomes (1)

• 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.

  7 days

Secondary Outcomes (7)

• All-cause mortality for 28 days after randomization

  28 days

• Intensive Care Unit (ICU) or Intermediate Respiratory Care Unit (IRCU) transfer for 28 days after randomization

  28 days

• Clinical status of the patient using the ordinal scale of the WHO

  7 days

• Sequential Organ Failure Assessment (SOFA) score on admission, and 4 and 7 days after randomization

  7 days

• Hospital length of stay

  Number of days between admission date and discharge

Study Arms (2)

Dexamethasone

EXPERIMENTAL

Dexamethasone base 6 mg once daily for seven days

Drug: Dexamethasone

Standard of care

ACTIVE COMPARATOR

Standard care therapy

Drug: Dexamethasone

Interventions

Dexamethasone DRUG

Dexamethasone base 6 mg once daily for seven days

Also known as: Dexametasona kern pharma solution for injection 4 mg/ml

Dexamethasone; Standard of care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• Patients who are already enrolled in another clinical trial.

Sponsors & Collaborators

• Hospital Universitario Infanta Leonor: lead
• Fundación para la Investigación e Innovación Biomédica del Hospital Universitario Infanta Leonor: collaborator
• Kern Pharma, S.L.: collaborator

Study Sites (3)

Hospital Universitario Infanta Leonor

Madrid, 28031, Spain

RECRUITING

Hospital Universitario Clínico San Carlos

Madrid, 28040, Spain

RECRUITING

Hospital Emergencias Enfermera Isabel Zendal

Madrid, 28055, Spain

RECRUITING

Related Publications (14)

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  PMID: 32105632 RESULT

• Siddiqi 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.

  PMID: 32362390 RESULT

• Chen 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.

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• RECOVERY 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.

  PMID: 32678530 RESULT

• WHO/2019-nCoV/Corticosteroids/2020.1

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• 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.

  PMID: 32171390 RESULT

• Monedero 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.

  PMID: 33397463 RESULT

• Fadel 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.

  PMID: 32427279 RESULT

• Zhou 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.

  PMID: 32171076 RESULT

• Ruan 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.

  PMID: 32125452 RESULT

• Huang 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.

  PMID: 31986264 RESULT

• Guan 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.

  PMID: 32109013 RESULT

• Franco-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.

  PMID: 39086948 DERIVED

• Franco-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.

  PMID: 36109825 DERIVED

MeSH Terms

Conditions

COVID-19; Respiratory Distress Syndrome; Pneumonia, Viral

Interventions

Dexamethasone; Injections

Condition Hierarchy (Ancestors)

Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Drug Administration Routes; Drug Therapy; Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: The study participants and the clinicians who will evaluate post-treatment outcomes will be known to group assignment. The clinical research team will not be blinded to group assignment
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a prospective, multicentre, phase 3, parallel-group, randomized and controlled trial that is open-label to investigators, participants and clinical outcome assessors

Study Record Dates

• First Submitted: March 18, 2021
• First Posted: April 8, 2021
• Study Start: June 10, 2021
• Primary Completion: February 28, 2023
• Study Completion: March 30, 2023
• Last Updated: March 1, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

ES (3)