COVID-19-associated ARDS Treated With Dexamethasone: Alliance Covid-19 Brasil III (CoDEX)

COVID-19-associated ARDS Treated With DEXamethasone: an Open-label, Randomized, Controlled Trial: CoDEX (Alliance Covid-19 Brasil III)

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.

Study Overview

• Status: Terminated
• Conditions: Coronavirus Infection; Pneumonia, Viral; Acute Respiratory Distress Syndrome
• Intervention / Treatment: Drug: Dexamethasone

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.

• Study Type: Interventional
• Enrollment (Actual): 299
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • São Paulo, Brazil
    • Universidade Federal de São Paulo
  • São Paulo, Brazil
    • Sociedade Beneficente de Senhoras Hospital Sirio-Libanes
  • São Paulo, Brazil
    • Hospital Israelita Albert Einstein
  • São Paulo, Brazil
    • Associacao Beneficente Siria
  • São Paulo, Brazil
    • Secretaria de Saúde do Estado de São Paulo
  • São Paulo, Brazil
    • Santa Casa de Misericórdia
  • São Paulo, Brazil
    • Real e Benemérita Associação Portuguesa de Beneficência/SP
  • São Paulo, Brazil
    • Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da USP - HCFMRP
  • São Paulo, Brazil
    • Prevent Senior Private Operadora de Saude Ltda
  • Bahia
    • Salvador, Bahia, Brazil
      • Hospital Ana Nery
  • Distrito Federal
    • Brasília, Distrito Federal, Brazil
      • Instituto de Cardiologia do Distrito Federal
  • Esoírito Santo
    • Colatina, Esoírito Santo, Brazil
      • Fundação Social Rural de Colatina
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil
      • Hospital Vera Cruz AS
    • Poços De Caldas, Minas Gerais, Brazil
      • Hospital Maternidade E Pronto Socorro Santa Lucia Ltda
  • Paraná
    • Londrina, Paraná, Brazil
      • Universidade Estadual de Londrina
  • Rio Grande Do Norte
    • Natal, Rio Grande Do Norte, Brazil
      • Eurolatino Natal Pesquisas Medicas Ltda
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil
      • Irmandade da Santa Casa de Misericordia de Porto Alegre
  • Santa Catarina
    • Blumenau, Santa Catarina, Brazil
      • Maestri E Kormann Consultoria Medico-Cientifica
    • Criciúma, Santa Catarina, Brazil
      • Sociedade Literaria e Caritativa Santo Agostinho
  • São Paulo
    • Barretos, São Paulo, Brazil
      • Fundacao Pio XII
    • Votuporanga, São Paulo, Brazil
      • Santa Casa de Misericórdia de Votuporanga

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Intervention group; 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).	Drug: Dexamethasone; Dexamethasone administration for 10 consecutive days after randomization.; Other Names: Decadron; Hexadrol; Dexasone; Maxidex; Diodex
NO_INTERVENTION: Control; Standard treatment (according to the treatment protocol for 2019-nCoV infection).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ventilator-free days	Ventilator-free days, defined as alive and free from mechanical ventilation, at 28 days after randomization.	28 days after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the clinical status	Evaluation of the clinical status of patients on the 15th day after randomization defined by the 6-point Ordinal Scale, this scale ranges from 1 (Not hospitalized) to 6 (Death) with higher scores meaning worse outcomes.	15 days after randomization
All-cause mortality	All-cause mortality rates at 28 days after randomization.	28 days after randomization
Mechanical ventilation duration	Number of days of mechanical ventilation from randomization to day 28.	28 days after randomization
Sequential Organ Failure Assessment (SOFA) Score	Sequential Organ Failure Assessment (SOFA) Score 48 hours, 72 hours and 7 days after randomization	Score at 48 hours, 72 hours and 7 days after randomization

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intensive Care Unit free days	Intensive Care Unit free days, defined as alive and discharged from the intensive care unit, at 28 days after randomization.	28 days after randomization

Collaborators and Investigators

• Sponsor: Hospital Sirio-Libanes
• Collaborators: Hospital Israelita Albert Einstein; Ache Laboratorios Farmaceuticos S.A.; Hospital do Coracao; Brazilian Research In Intensive Care Network
• Investigators: Principal Investigator: Luciano Cesar Pontes Azevedo, Ph.D, Teaching Director of Teaching & Research Institute Sírio-Libanês Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 13, 2020
• Primary Completion (ACTUAL): July 22, 2020
• Study Completion (ACTUAL): July 22, 2020

Study Registration Dates

• First Submitted: March 26, 2020
• First Submitted That Met QC Criteria: March 27, 2020
• First Posted (ACTUAL): March 31, 2020

Study Record Updates

• Last Update Posted (ACTUAL): August 7, 2020
• Last Update Submitted That Met QC Criteria: August 5, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: ARDS; Dexamethasone; Respiratory failure; Corticosteroids; 2019-nCOV; SARS-CoV2 virus
• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Coronavirus Infections; Pneumonia, Viral; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone
• Other Study ID Numbers: CAAE: 30227020.5.1001.0008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No