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

Phase 3

Terminated

• Conditions: Coronavirus Infection; Pneumonia, Viral; Acute Respiratory Distress Syndrome
• Interventions: Drug: Dexamethasone

• Registration Number: NCT04327401
• Lead Sponsor: Hospital Sirio-Libanes

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 Timeline

• Study First Submitted: 2020-03-26
• Study First Submitted QC: 2020-03-27
• Study First Posted: 2020-03-31
• Study Start: 2020-04-13
• Primary Completion: 2020-07-22
• Study Completion: 2020-07-22
• Status Verified: 2020-08
• Last Update Submitted: 2020-08-05
• Last Update Posted: 2020-08-07

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 299

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intervention group	Dexamethasone	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).

Primary Outcome Measures

Name	Time	Method
Ventilator-free days	28 days after randomization	Ventilator-free days, defined as alive and free from mechanical ventilation, at 28 days after randomization.

Secondary Outcome Measures

Name	Time	Method
All-cause mortality	28 days after randomization	All-cause mortality rates at 28 days after randomization.
Mechanical ventilation duration	28 days after randomization	Number of days of mechanical ventilation from randomization to day 28.
Evaluation of the clinical status	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.
Sequential Organ Failure Assessment (SOFA) Score	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

Trial Locations

Locations (21)

Fundação Social Rural de Colatina; 🇧🇷 Colatina, Esoírito Santo, 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

Associacao Beneficente Siria; 🇧🇷 São Paulo, Brazil

Prevent Senior Private Operadora de Saude Ltda; 🇧🇷 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

Secretaria de Saúde do Estado de São Paulo; 🇧🇷 São Paulo, Brazil

Santa Casa de Misericórdia; 🇧🇷 São Paulo, Brazil

Sociedade Beneficente de Senhoras Hospital Sírio-Libanês; 🇧🇷 São Paulo, Brazil

Universidade Federal de São Paulo; 🇧🇷 São Paulo, Brazil

Sociedade Literaria e Caritativa Santo Agostinho; 🇧🇷 Criciúma, Santa Catarina, Brazil

Santa Casa de Misericordia de Votuporanga; 🇧🇷 Votuporanga, São Paulo, Brazil

Instituto de Cardiologia do Distrito Federal; 🇧🇷 Brasília, Distrito Federal, Brazil

Hospital Vera Cruz AS; 🇧🇷 Belo Horizonte, Minas Gerais, Brazil

Real e Benemérita Associação Portuguesa de Beneficência/SP; 🇧🇷 São Paulo, Brazil

Hospital Ana Nery; 🇧🇷 Salvador, Bahia, Brazil

Universidade Estadual de Londrina; 🇧🇷 Londrina, Paraná, Brazil

Maestri E Kormann Consultoria Medico-Cientifica; 🇧🇷 Blumenau, Santa Catarina, Brazil

Fundação Pio XII; 🇧🇷 Barretos, São Paulo, Brazil

Eurolatino Natal Pesquisas Médicas Ltda; 🇧🇷 Natal, Rio Grande Do Norte, Brazil