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

Acute Respiratory Distress Syndrome Clinical Trial

— CoDEX  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04327401
• Other study ID #: CAAE: 30227020.5.1001.0008
• Status: Terminated
• Phase: Phase 3
• Start date: April 13, 2020
• Est. completion date: July 22, 2020

Study information

• Verified date: August 2020
• Source: Hospital Sirio-Libanes
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 299
• Est. completion date: July 22, 2020
• Est. primary completion date: July 22, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Distress Syndrome
• Coronavirus Infection
• Coronavirus Infections
• Pneumonia, Viral
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn
• Severe Acute Respiratory Syndrome

Intervention

Drug:
• Dexamethasone
Dexamethasone administration for 10 consecutive days after randomization.

Locations

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

Sponsors (5)

Lead Sponsor	Collaborator
Hospital Sirio-Libanes	Ache Laboratorios Farmaceuticos S.A., Brazilian Research In Intensive Care Network, Hospital do Coracao, Hospital Israelita Albert Einstein

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Primary	Ventilator-free days	Ventilator-free days, defined as alive and free from mechanical ventilation, at 28 days after randomization.	28 days after randomization
Secondary	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
Secondary	All-cause mortality	All-cause mortality rates at 28 days after randomization.	28 days after randomization
Secondary	Mechanical ventilation duration	Number of days of mechanical ventilation from randomization to day 28.	28 days after randomization
Secondary	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