Dexamethasone for COVID-19 Related ARDS: a Multicenter, Randomized Clinical Trial

High Versus Low Dose Dexamethasone for the Treatment of COVID-19 Related ARDS: a Multicenter and Randomized Open-label Clinical Trial

There is compelling data indicating that there is an excessive inflammatory response in some patients with COVID-19 leading them to develop ARDS that can be severe with a very poor prognosis. Many of these patients require very long mechanical ventilation times to survive, which have led to the collapse of the health system in some regions of the world. The current evidence for the treatment of these severe forms is inconsistent and most scientific societies and governmental or international organizations recommend evaluating treatments with randomized clinical trials. Corticosteroids, being non-specific anti-inflammatory drugs, could shorten the duration of respiratory failure and improve the prognosis. Due to the lack of solid data available regarding this serious disease, our objective is to randomly evaluate the efficacy and safety of the use of dexamethasone, a parenteral corticosteroid approved in Argentina, in patients with ARDS with confirmed respiratory infection due to SARS-CoV-2 (COVID-19).

After RECOVERY trial prepublication, low dose (6 mg QD for 10 days) dexamethasone was recommended as the usual care treatment for severe COVID-19. At this time only 3 patients had been included in the trial. Thus, we updated our recommendations for centers and decided to compare two different doses of this glucocorticoid for the treatment of ADRS due to COVID-19.

Study Overview

• Status: Terminated
• Conditions: Covid-19; Respiratory Distress Syndrome, Adult
• Intervention / Treatment: Drug: High-Dose Dexamethasone

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Caba, Argentina, 1431
    • Hospital Universitario Sede Saaveda - IUC CEMIC
  • Ciudad Autonoma de Buenos Aires, Argentina, 1425
    • Hospital Universitario Sede Pombo - IUC CEMIC
  • Ciudad Autonoma de Buenos Aires, Argentina
    • Sanatorio Sagrado Corazon
  • Ciudad Autónoma de Buenos Aires, Argentina, 1425
    • Clínica Bazterrica

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:

• ARDS according to Berlin's definition
• PCR confirmed COVID-19
• Length of mechanical ventilation less or equal to 72 hours

Exclusion Criteria:

• Pregnancy or breast-feeding women
• Terminal illness with very poor prognosis according to the investigator judgement
• Therapeutic limitation
• Known immunocompromised condition
• Chronic use of systemic corticosteroids
• Participation in another randomized crinical trial
• More than 5 days of treatment of low dose dexamethasone for COVID-19
• Abscence of informed consent
• Active participation in other randomized clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High dose Dexamethasone; Intravenous Dexamethasone 16 mg qd from day 1 to 5 followed by 8 mg qd from day 6 to 10	Drug: High-Dose Dexamethasone; IV Dexamethasone administered once daily: 16 mg from day 1 to 5 and 8 mg from day 6 to 10; Other Names: Corticosteroid
No Intervention: Usual care - low dose Dexamethasone; Intravenous Dexamethasone 6 mg qd for 10 days based on RECOVERY trial

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ventilator-free days at 28 days	Days without ventilator support in the first 28 days following randomization	28 days after randomization
Time to successful discontinuation from mechanical ventilation	Time to event (successful discontinuation from mechanical ventilation)	28 days after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
28-days mortality	Dead rate within 28 days of randomization	28 days after randomization
Rate of nosocomial infections	Rate of ventilator associated pneumonia, blood stream infection, urinary tract infection or candidemia in the first 28 days following randomization	28 days after randomization
SOFA variation	Variation in SOFA over the first 10 days after randomization	10 days after randomization
Use of prone position	Cumulative hours spent on prone position	10 days after randomization
Delirium	Frequency of delirium at ICU discharge	28 days after randomization
Muscle weakness	mMRC score at ICU discharge	28 days after randomization
90-day mortality	Death rate within 90 days of randomization	90 days after randomization
Peak daily blood glucose	Interaction between treatment and daily change in glucose	10 days after randomization

Collaborators and Investigators

• Sponsor: Centro de Educación Medica e Investigaciones Clínicas Norberto Quirno
• Investigators: Principal Investigator: Pablo O Rodriguez, MD, Centro de Educación Medica e Investigaciones Clínicas Norberto Quirno; Principal Investigator: Luis P Maskin, MD, Centro de Educación Medica e Investigaciones Clínicas Norberto Quirno

Publications and helpful links

General Publications

• Maskin LP, Olarte GL, Palizas F Jr, Velo AE, Lurbet MF, Bonelli I, Baredes ND, Rodriguez PO. High dose dexamethasone treatment for Acute Respiratory Distress Syndrome secondary to COVID-19: a structured summary of a study protocol for a randomised controlled trial. Trials. 2020 Aug 26;21(1):743. doi: 10.1186/s13063-020-04646-y.

Helpful Links

• Protocol publication

Study record dates

Study Major Dates

• Study Start (Actual): May 21, 2020
• Primary Completion (Actual): April 5, 2021
• Study Completion (Actual): May 21, 2021

Study Registration Dates

• First Submitted: May 16, 2020
• First Submitted That Met QC Criteria: May 18, 2020
• First Posted (Actual): May 20, 2020

Study Record Updates

• Last Update Posted (Actual): June 2, 2021
• Last Update Submitted That Met QC Criteria: May 28, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; COVID-19; 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: 1264

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