Clinical trial NCT04327401: COVID-19-associated ARDS Treated With Dexamethasone: Alliance Covid-19 Brasil III
Official title: COVID-19-associated ARDS Treated With DEXamethasone: an Open-label, Randomized, Controlled Trial: CoDEX (Alliance Covid-19 Brasil III)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Coronavirus Infection
Pneumonia, Viral
Acute Respiratory Distress Syndrome
Keywords: SARS-CoV2 virus
2019-nCOV
Dexamethasone
ARDS
Corticosteroids
Respiratory failure
Lead sponsor: Hospital Sirio-Libanes
Sponsor class: OTHER
Collaborators: name: Hospital Israelita Albert Einstein
name: Hospital do Coracao
name: Brazilian Research In Intensive Care Network
name: Ache Laboratorios Farmaceuticos S.A.
First posted: 2020-03-31
Enrollment: 299
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 1. Dexamethasone. After randomization, dexamethasone 20mg IV 1x/day for 5 days, followed by 10mg IV 1xd for 5 days + standard treatment (according to the treatment protocol for 2019-nCoV infection).
2. Standard treatment (according to the treatment protocol for 2019-nCoV infection).
Primary purpose: TREATMENT

Brief summary: The Severe Acute Respiratory Syndrome COronaVirus 2 (SARS-CoV2) is a new and recognized infectious disease of the respiratory tract. Most cases are mild or asymptomatic. However, around 5% of all patients develop Acute Respiratory Distress Syndrome (ARDS), which is the leading mortality cause in these patients. Corticosteroids have been tested in deferent scenarios of ARDS, including viral pneumonia, and the early use of dexamethasone is safe and appears to reduce the duration of mechanical ventilation in ARDS patients. Nevertheless, no large, randomized, controlled trial was performed evaluating the role of corticosteroids in patients with ARDS due SARS-CoV2 virus. Therefore, the present study will evaluate the effectiveness of dexamethasone compared to control (no corticosteroids) in patients with moderate and severe ARDS due to SARS-CoV2 virus.

Detailed description: The Severe Acute Respiratory Syndrome COronaVirus 2 (SARS-CoV2) is a new and recognized infectious disease of the respiratory tract, and its outbreak deemed a pandemic in early March 2020. Estimates show around 5% of all patients develop Acute Respiratory Distress Syndrome (ARDS), which due to its severity, consumes most Intensive Care Units (ICU) resources and is the leading mortality cause in this population. Given its burden, therapies that reduce the duration of mechanical ventilation or decrease the morbimortality are needed. Studies indicate that inflammation and cytokine storm might be involved in the pathophysiological pathway to ARDS in these patients. Corticosteroids have been tested in deferent scenarios of ARDS, including viral pneumonia, and the early use of dexamethasone is safe and appears to reduce the duration of mechanical ventilation in ARDS patients. A recent small retrospective study evaluating the role of corticosteroids found no association between corticosteroids and hospital length of stay, virus clearance, and symptoms' duration. However, the retrospective nature of data, small sample size (31 patients), and no protocol for corticosteroids administration undermine its results. Therefore, the present study will evaluate the effectiveness of dexamethasone compared to control (no corticosteroids) in ventilator-free days at 28 days in patients with moderate and severe ARDS due to SARS-CoV2 virus in Brazil.

Eligibility criteria: Inclusion Criteria:

* Probable or confirmed infection by SARS-CoV2
* Intubated and mechanically ventilated
* Moderate/severe ARDS defined by the Berlin criteria (PaO2/FiO2 ≤200mmHg with PEEP ≥5cmH20)
* Onset of moderate/severe ARDS in less than 48 hours before randomization

Exclusion Criteria:

* Pregnancy or active lactation
* Known history of dexamethasone allergy
* Daily use of corticosteroids in the past 15 days
* Clinical indication for corticosteroids use for other diseases (i.e refractory septic shock)
* Patients who did use corticosteroids during hospital stay for periods equal or greater than two days
* Use of immunosuppressive drugs
* Cytotoxic chemotherapy in the past 21 days
* Neutropenia due to hematological or solid malignancies with bone marrow invasion
* Patient expected to die in the next 24 hours

Primary outcomes:
measure: Ventilator-free days
timeFrame: 28 days after randomization
Secondary outcomes:
measure: Evaluation of the clinical status
timeFrame: 15 days after randomization
measure: All-cause mortality
timeFrame: 28 days after randomization
measure: Mechanical ventilation duration
timeFrame: 28 days after randomization
measure: Sequential Organ Failure Assessment (SOFA) Score
timeFrame: Score at 48 hours, 72 hours and 7 days after randomization
Other outcomes:
measure: Intensive Care Unit free days
timeFrame: 28 days after randomization
Locations:
city: Salvador
country: Brazil
facility: Hospital Ana Nery
state: Bahia
city: Brasília
country: Brazil
facility: Instituto de Cardiologia do Distrito Federal
state: Distrito Federal
city: Colatina
country: Brazil
facility: Fundação Social Rural de Colatina
state: Esoírito Santo
city: Belo Horizonte
country: Brazil
facility: Hospital Vera Cruz AS
state: Minas Gerais
city: Poços De Caldas
country: Brazil
facility: Hospital Maternidade E Pronto Socorro Santa Lucia Ltda
state: Minas Gerais
city: Londrina
country: Brazil
facility: Universidade Estadual de Londrina
state: Paraná
city: Natal
country: Brazil
facility: Eurolatino Natal Pesquisas Médicas Ltda
state: Rio Grande Do Norte
city: Porto Alegre
country: Brazil
facility: Irmandade da Santa Casa de Misericordia de Porto Alegre
state: Rio Grande Do Sul
city: Blumenau
country: Brazil
facility: Maestri E Kormann Consultoria Medico-Cientifica
state: Santa Catarina
city: Criciúma
country: Brazil
facility: Sociedade Literaria e Caritativa Santo Agostinho
state: Santa Catarina
city: Barretos
country: Brazil
facility: Fundação Pio XII
state: São Paulo
city: Votuporanga
country: Brazil
facility: Santa Casa de Misericordia de Votuporanga
state: São Paulo
city: São Paulo
country: Brazil
facility: Associacao Beneficente Siria
city: São Paulo
country: Brazil
facility: Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da USP - HCFMRP
city: São Paulo
country: Brazil
facility: Hospital Israelita Albert Einstein
city: São Paulo
country: Brazil
facility: Prevent Senior Private Operadora de Saude Ltda
city: São Paulo
country: Brazil
facility: Real e Benemérita Associação Portuguesa de Beneficência/SP
city: São Paulo
country: Brazil
facility: Santa Casa de Misericórdia
city: São Paulo
country: Brazil
facility: Secretaria de Saúde do Estado de São Paulo
city: São Paulo
country: Brazil
facility: Sociedade Beneficente de Senhoras Hospital Sírio-Libanês
city: São Paulo
country: Brazil
facility: Universidade Federal de São Paulo
Study officials:
affiliation: Teaching Director of Teaching & Research Institute Sírio-Libanês Hospital
name: Luciano Cesar Pontes Azevedo, Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tomazini BM, Maia IS, Cavalcanti AB, Berwanger O, Rosa RG, Veiga VC, Avezum A, Lopes RD, Bueno FR, Silva MVAO, Baldassare FP, Costa ELV, Moura RAB, Honorato MO, Costa AN, Damiani LP, Lisboa T, Kawano-Dourado L, Zampieri FG, Olivato GB, Righy C, Amendola CP, Roepke RML, Freitas DHM, Forte DN, Freitas FGR, Fernandes CCF, Melro LMG, Junior GFS, Morais DC, Zung S, Machado FR, Azevedo LCP; COALITION COVID-19 Brazil III Investigators. Effect of Dexamethasone on Days Alive and Ventilator-Free in Patients With Moderate or Severe Acute Respiratory Distress Syndrome and COVID-19: The CoDEX Randomized Clinical Trial. JAMA. 2020 Oct 6;324(13):1307-1316. doi: 10.1001/jama.2020.17021.