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

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

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.

Study Overview

• Status: Completed
• Conditions: Covid19; Corticosteroids
• Intervention / Treatment: Drug: Dexamethasone low dose; Drug: Dexamethasone high dose

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 Type: Interventional
• Enrollment (Actual): 198
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • A Coruña
    • Santiago de Compostela, A Coruña, Spain, 15866
      • University Clinical Hospital of Santiago de Compostela

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:

• 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.

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
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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with treatment failure at day 11	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).	Day 11 after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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)	10 days after randomization
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

Collaborators and Investigators

• Sponsor: Manuel Taboada Muñiz
• Investigators: Principal Investigator: Manuel Taboada Muñiz, Ph.D., University Clinical Hospital of Santiago de Compostela

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2021
• Primary Completion (Actual): August 31, 2021
• Study Completion (Actual): August 31, 2021

Study Registration Dates

• First Submitted: January 23, 2021
• First Submitted That Met QC Criteria: January 26, 2021
• First Posted (Actual): January 27, 2021

Study Record Updates

• Last Update Posted (Actual): October 20, 2021
• Last Update Submitted That Met QC Criteria: October 19, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: COVID19; respiratory failure; corticosteroids
• 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; COVID-19; Respiratory Insufficiency; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Dexamethasone; Dexamethasone acetate; BB 1101
• Other Study ID Numbers: HIGHLOWDEXA-COVID; 2020-005702-25 (EudraCT Number)

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
• product manufactured in and exported from the U.S.: No