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

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ClinicalTrials.gov Identifier: NCT04327401
Recruitment Status : Terminated (The Data Monitoring Committee recommended to stop the trial based on the Recovery Trial results, which was accepted by the CoDEX Steering Committee.)
First Posted : March 31, 2020
Last Update Posted : August 7, 2020
Sponsor:
Collaborators:
Hospital Israelita Albert Einstein
Hospital do Coracao
Brazilian Research In Intensive Care Network
Ache Laboratorios Farmaceuticos S.A.
Information provided by (Responsible Party):
Luciano Cesar Pontes de Azevedo, Hospital Sirio-Libanes

Tracking Information
First Submitted Date  ICMJE March 26, 2020
First Posted Date  ICMJE March 31, 2020
Last Update Posted Date August 7, 2020
Actual Study Start Date  ICMJE April 13, 2020
Actual Primary Completion Date July 22, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 27, 2020)
Ventilator-free days [ Time Frame: 28 days after randomization ]
Ventilator-free days, defined as alive and free from mechanical ventilation, at 28 days after randomization.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 30, 2020)
  • Evaluation of the clinical status [ Time Frame: 15 days after randomization ]
    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.
  • All-cause mortality [ Time Frame: 28 days after randomization ]
    All-cause mortality rates at 28 days after randomization.
  • Mechanical ventilation duration [ Time Frame: 28 days after randomization ]
    Number of days of mechanical ventilation from randomization to day 28.
  • Sequential Organ Failure Assessment (SOFA) Score [ Time Frame: Score at 48 hours, 72 hours and 7 days after randomization ]
    Sequential Organ Failure Assessment (SOFA) Score 48 hours, 72 hours and 7 days after randomization
Original Secondary Outcome Measures  ICMJE
 (submitted: March 27, 2020)
  • Evaluation of the clinical status [ Time Frame: 15 days after randomization ]
    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.
  • All-cause mortality [ Time Frame: 28 days after randomization ]
    All-cause mortality rates at 28 days after randomization.
  • Mechanical ventilation duration [ Time Frame: 28 days after randomization ]
    Number of days of mechanical ventilation from randomization to day 28.
  • Sequential Organ Failure Assessment (SOFA) Score [ Time Frame: Score 48h, 72h and 7 days after randomization ]
    Sequential Organ Failure Assessment (SOFA) Score 48 hours, 72 hours and 7 days after randomization
Current Other Pre-specified Outcome Measures
 (submitted: April 13, 2020)
Intensive Care Unit free days [ Time Frame: 28 days after randomization ]
Intensive Care Unit free days, defined as alive and discharged from the intensive care unit, at 28 days after randomization.
Original Other Pre-specified Outcome Measures
 (submitted: March 27, 2020)
  • Ventilator-free days in the subgroup of patients with secondary hemophagocytic lymphohistiocytosis [ Time Frame: 28 days after randomization ]
    Ventilator-free days at 28 days after randomization in the subgroup of patients with secondary hemophagocytic lymphohistiocytosis (sHLH) defined using the HScore, with an HScore cutoff of ≥169 needed to diagnosis sHLH
  • Ventilator-free days in patients with laboratory-confirmed SARS-CoV2 [ Time Frame: 28 days after randomization ]
    Ventilator-free days at 28 days after randomization in the subgroup of patients with laboratory-confirmed SARS-CoV2 infection
 
Descriptive Information
Brief Title  ICMJE COVID-19-associated ARDS Treated With Dexamethasone: Alliance Covid-19 Brasil III
Official Title  ICMJE COVID-19-associated ARDS Treated With DEXamethasone: an Open-label, Randomized, Controlled Trial: CoDEX (Alliance Covid-19 Brasil III)
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
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).
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Coronavirus Infection
  • Pneumonia, Viral
  • Acute Respiratory Distress Syndrome
Intervention  ICMJE Drug: Dexamethasone
Dexamethasone administration for 10 consecutive days after randomization.
Other Names:
  • Decadron
  • Dexasone
  • Diodex
  • Hexadrol
  • Maxidex
Study Arms  ICMJE
  • 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).
    Intervention: Drug: Dexamethasone
  • No Intervention: Control
    Standard treatment (according to the treatment protocol for 2019-nCoV infection).
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: August 5, 2020)
299
Original Estimated Enrollment  ICMJE
 (submitted: March 27, 2020)
290
Actual Study Completion Date  ICMJE July 22, 2020
Actual Primary Completion Date July 22, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Brazil
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04327401
Other Study ID Numbers  ICMJE CAAE: 30227020.5.1001.0008
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Luciano Cesar Pontes de Azevedo, Hospital Sirio-Libanes
Study Sponsor  ICMJE Hospital Sirio-Libanes
Collaborators  ICMJE
  • Hospital Israelita Albert Einstein
  • Hospital do Coracao
  • Brazilian Research In Intensive Care Network
  • Ache Laboratorios Farmaceuticos S.A.
Investigators  ICMJE
Principal Investigator: Luciano Cesar Pontes Azevedo, Ph.D Teaching Director of Teaching & Research Institute Sírio-Libanês Hospital
PRS Account Hospital Sirio-Libanes
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP