HIGHLOWDEXA: Low or High Dose of Dexamethasone in Patients With Respiratory Failure by COVID-19

Sponsor

Manuel Taboada Muñiz (Other)

Overall Status

Completed

CT.gov ID

NCT04726098

Collaborator

(none)

198

Enrollment

Location

Arms

7.5

Actual Duration (Months)

26.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

After RECOVERY trial publication, low dose (6 mg dexamethasone for 10 days) was recommended as the usual care treatment in hospitalized patients with respiratory failure by COVID-19 needing oxygen therapy. RECOVERY trial showed how the use of dexamethasone 6 mg / day for ten days compared to standard treatment without the use of corticosteroids in hospitalized patients reduced mortality at 28 days (22.9% with dexamethasone vs 25.7% without dexamethasone). In the dexamethasone group, the incidence of mortality was lower than standard treatment in patients with hypoxia and the need for mechanical ventilation (29.3% with dexamethasone vs 41.4% without dexamethasone), in patients admitted to the hospital ward with a need for oxygen therapy (23.3% with dexamethasone vs 26.2% without dexamethasone), but they did not find differences between those admitted patients who did not need oxygen therapy. There are two other studies (DEXA-COVID-19 and CoDEX) where they observed benefits of the use of dexamethasone 20 mg / day 5 days, and 10 mg / day 5 days (total 10 days) in patients admitted for respiratory distress syndrome (ARDS) and COVID-19. At present, it is unclear what dose of dexamethasone is most beneficial in patients with COVID-19 and respiratory failure.

Condition or Disease	Intervention/Treatment	Phase
Covid19 Corticosteroids	Drug: Dexamethasone high dose Drug: Dexamethasone low dose	Phase 4

Detailed Description

Objective: The investigators aim to assess the efficacy of high dose of dexamethasone (20 mg / day 5 days, and 10 mg/day 5 days) versus low dose of dexamethasone (6 mg/day 10 days) in patients with respiratory failure by COVID-19.

Study Design

Study Type:

Interventional

Actual Enrollment :

198 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized, controlled, open-label trial involving hospitalized adult patients with respiratory failure needing oxygen therapy, caused by COVID-19.Randomized, controlled, open-label trial involving hospitalized adult patients with respiratory failure needing oxygen therapy, caused by COVID-19.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Efficacy of Low or High Dose of Dexamethasone in Patients With Respiratory Failure by COVID-19

Actual Study Start Date :

Jan 15, 2021

Actual Primary Completion Date :

Aug 31, 2021

Actual Study Completion Date :

Aug 31, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Low dose group Dexamethasone 6mg/day for 10 days	Drug: Dexamethasone low dose Low doses: dexamethasone 6 mg/day 10 days.
Active Comparator: High dose group Dexamethasone 20mg/day for 5 days + Dexamethasone 10mg/day for 5 days (Total 10 days)	Drug: Dexamethasone high dose High doses: dexamethasone 20 mg/day 5 days + 10 mg/day 5 days (total 10 days)

Arm

Intervention/Treatment

Active Comparator: Low dose group

Dexamethasone 6mg/day for 10 days

Drug: Dexamethasone low dose

Low doses: dexamethasone 6 mg/day 10 days.

Active Comparator: High dose group

Dexamethasone 20mg/day for 5 days + Dexamethasone 10mg/day for 5 days (Total 10 days)

Drug: Dexamethasone high dose

High doses: dexamethasone 20 mg/day 5 days + 10 mg/day 5 days (total 10 days)

Outcome Measures

Primary Outcome Measures

Percentage of patients with treatment failure at day 11 [Day 11 after randomization]
defined as death, need of ICU and extracorporeal membrane oxygenation, need of non-invasive ventilation or nasal high-flow oxygen therapy, or worsening of the condition clinic of the patient during treatment (two of these: need to increase Fraction of inspired oxygen inspired>20%, need for fraction inspired oxygenation>50%, increase in respiratory rate>25, increase in inflammatory markers).

Secondary Outcome Measures

Percentage of patients without the need for oxygen support at day 11. [Day 11 after randomization]
28-days mortality [28 days after randomization]
90-days mortality [90 days after randomization]
Clinical status of patients using the World Health Organization 7-point Ordinal Scale for clinical improvement during 10 days of treatment [10 days after randomization]
1:Not hospitalized, 2:Hospitalized and not treatment, 3: Hospitalized with treatment, not requiring supplemental oxygen, 4:Hospitalized requiring supplemental oxygen, 5:Hospitalized, requiring non-invasive ventilation or nasal high-flow oxygen therapy, 6: Hospitalized requiring invasive ventilation or Extracorporeal (ECMO)
Percentage of patients needing Intensive Care Unit admission [28 days after randomization]
Percentage of patients needing invasive mechanical ventilation or extracorporeal membrane oxygenation [28 days after randomization]
Percentage of patients needing non-invasive ventilation or nasal high-flow oxygen therapy [28 days after randomization]
Length of stay in the hospital [90 days after randomization]
Infectious complications during hospital admission [90 days after randomization]
Adverse drug reactions [11 days after randomization]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 18 years or older.
Hospitalized COVID-19 patients admitted to the Hospital.
Patients requiring supplemental oxygen. Level 4 using the World Health Organization 7-point Ordinal Scale for clinical improvement
Patients requiring corticosteroids (dexamethasone) according to Hospital protocol.

Exclusion Criteria:

Pregnancy or active lactation.
Patient is expected to die in the next 48 hours.
Known history of dexamethasone allergy or known contraindication to the use of corticosteroids.
Daily use of corticosteroids in the past 15 days.
Indication for corticosteroids use for other clinical conditions (e.g. refractory septic shock).
Consent refusal for participating in the trial.
Different level of 4 in Level 4 using the World Health Organization 7-point Ordinal Scale for clinical improvement.