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

Sponsor

Centro de Educación Medica e Investigaciones Clínicas Norberto Quirno (Other)

Overall Status

Terminated

CT.gov ID

NCT04395105

Collaborator

(none)

100

Enrollment

Locations

Arms

Actual Duration (Months)

Patients Per Site

2.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Respiratory Distress Syndrome, Adult Covid-19	Drug: High-Dose Dexamethasone	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

May 21, 2020

Actual Primary Completion Date :

Apr 5, 2021

Actual Study Completion Date :

May 21, 2021

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Hospital Universitario Sede Saaveda - IUC CEMIC	Caba	Argentina	1431
2	Hospital Universitario Sede Pombo - IUC CEMIC	Ciudad Autonoma de Buenos Aires	Argentina	1425
3	Sanatorio Sagrado Corazon	Ciudad Autonoma de Buenos Aires	Argentina
4	Clínica Bazterrica	Ciudad Autónoma de Buenos Aires	Argentina	1425

Sponsors and Collaborators

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