Clinical trial NCT04726098: Low or High Dose of Dexamethasone in Patients With Respiratory Failure by COVID-19
Official title: Efficacy of Low or High Dose of Dexamethasone in Patients With Respiratory Failure by COVID-19
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Covid19
Corticosteroids
Keywords: COVID19
respiratory failure
corticosteroids
Lead sponsor: Hospital Clinico Universitario de Santiago
Sponsor class: OTHER
First posted: 2021-01-27
Enrollment: 198
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, controlled, open-label trial involving hospitalized adult patients with respiratory failure needing oxygen therapy, caused by COVID-19.
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of patients with treatment failure at day 11
timeFrame: Day 11 after randomization
Secondary outcomes:
measure: Percentage of patients without the need for oxygen support at day 11.
timeFrame: Day 11 after randomization
measure: 28-days mortality
timeFrame: 28 days after randomization
measure: 90-days mortality
timeFrame: 90 days after randomization
measure: Clinical status of patients using the World Health Organization 7-point Ordinal Scale for clinical improvement during 10 days of treatment
timeFrame: 10 days after randomization
measure: Percentage of patients needing Intensive Care Unit admission
timeFrame: 28 days after randomization
measure: Percentage of patients needing invasive mechanical ventilation or extracorporeal membrane oxygenation
timeFrame: 28 days after randomization
measure: Percentage of patients needing non-invasive ventilation or nasal high-flow oxygen therapy
timeFrame: 28 days after randomization
measure: Length of stay in the hospital
timeFrame: 90 days after randomization
measure: Infectious complications during hospital admission
timeFrame: 90 days after randomization
measure: Adverse drug reactions
timeFrame: 11 days after randomization
Other outcomes:
Locations:
city: Santiago de Compostela
country: Spain
facility: University Clinical Hospital of Santiago de Compostela
state: A Coruña
Study officials:
affiliation: University Clinical Hospital of Santiago de Compostela
name: Manuel Taboada Muñiz, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Taboada M, Rodriguez N, Varela PM, Rodriguez MT, Abelleira R, Gonzalez A, Casal A, Diaz Peromingo JA, Lama A, Dominguez MJ, Rabade C, Paez EM, Riveiro V, Pernas H, Beceiro MDC, Caruezo V, Naveira A, Carinena A, Cabaleiro T, Estany-Gestal A, Zarra I, Pose A, Valdes L, Alvarez-Escudero J. Effect of high versus low dose of dexamethasone on clinical worsening in patients hospitalised with moderate or severe COVID-19 pneumonia: an open-label, randomised clinical trial. Eur Respir J. 2022 Aug 4;60(2):2102518. doi: 10.1183/13993003.02518-2021. Print 2022 Aug.