Glucocorticoids in COVID-19 (CORTIVID)

Study Overview
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Brief Summary
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Around 30% of admitted patients with COVID-19 pneumonia develop a hyper-inflammatory state whose progression to an acute respiratory distress syndrome (ARSD) could be prevented by the early initiation of immune-modulatory agents. The role of glucocorticoids (GC) in this setting remains controversial. This study aims to assess the safety and effectiveness of GC pulses to improve the clinical outcomes of patients with COVID-19 pneumonia with risen inflammatory biomarkers.

Official Title
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Treatment of COVID-19 Pneumonia With Glucocorticoids. A Randomized Controlled Trial

Conditions
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Covid-19 Pneumonia

Intervention / Treatment
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* Drug: Methylprednisolone
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years old. Diagnosis of SARS-CoV-2 pneumonia confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) on nasopharyngeal swab or sputum according to the recommendations of the Spanish Ministry of Health. Length of symptoms consistent with COVID-19 ≥7 days. Hospital admission. At least one of the following: CRP >60 mg/L, IL-6 >40 pg/mL, ferritin >1000 μg/L. Acceptation of informed consent Exclusion Criteria: Allergy or contraindication to any of the drugs under study. SpO2 <90% (in air ambient) or PaO2 <60 mmHg (in ambient air) or PaO2/FiO2 <300 mmHg. Ongoing treatment with glucocorticoids, immunosuppressive, or biologic drugs with another indication. Decompensated diabetes mellitus. Uncontrolled hypertension. Psychotic or manic disorder. Active cancer. Pregnancy or lactation. Clinical or biochemical suspicion (procalcitonin >0.5 ng/mL) of active infection other than SARS-CoV-2. Out-of-hospital management patient. Conservative or palliative management patient. Participation in another clinical trial. Any important and uncontrolled medical, psychological, psychiatric, geographic or social problem that contraindicates the patient's participation in the trial or that does not allow adequate follow-up and adherence to the protocol and evaluation of the study results.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Methylprednisolone Arm<br>Standard of care plus Methylprednisolone | Drug: Methylprednisolone<br>* -A dose of 120 mg/day of methylprednisolone for 3 days, administered by intravenous infusión<br>|
| Placebo Comparator: Placebo Arm<br>Standard of care plus placebo | Other: Placebo<br>* -An infusion bag of 100 mL of 0.9% saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients developing treatment failure | • Death | At 14 days after randomization | 
| Proportion of patients developing treatment failure | • Need for admission in an intensive care unit (ICU) | At 14 days after randomization | 
| Proportion of patients developing treatment failure | • Need for mechanical ventilation | At 14 days after randomization | 
| Proportion of patients developing treatment failure | • Decrease in SpO2 <90% (in ambient air) or PaO2 <60 mmHg (in ambient air) or PaO2FiO2 <300 mmHg, associated with radiological impairment | At 14 days after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality at day 28 |  | At 28 days after randomization | 
| Proportion of patients requiring ICU admission |  | At 28 days after randomization | 
| Proportion of patients requiring rescue-therapy with tocilizumab |  | At 14 days after randomization | 
| Length of hospital stay | Time in days from randomization until the date of hospital discharge. | At 28 days after randomization | 
| Proportion of severe adverse events | Any undesirable experience related to the use of the studied drugs, which causes patient's death, life-threatening risk, hospitalization or extension of a previous hospitalization, disability or permanent damage, requires intervention to prevent permanent impairment or damage, or is considered medically relevant | At 28 days after randomization | 
| Proportion of bacterial, fungal or opportunistic infections |  | At 28 days after randomization | 
| Evolution of inflammatory biomarkers related to COVID-19 | Change in plasma levels of C-reactive protein (CRP) | At 14 days after randomization | 
| Evolution of inflammatory biomarkers related to COVID-19 | Change in plasma levels of ferritin | At 14 days after randomization | 
| Evolution of inflammatory biomarkers related to COVID-19 | Change in plasma levels of interleukin-6 (IL-6) | At 14 days after randomization | 
| Evolution of inflammatory biomarkers related to COVID-19 | Change in plasma levels of lactate dehydrogenase (LDH) | At 14 days after randomization | 
| Evolution of inflammatory biomarkers related to COVID-19 | Change in plasma levels of D-dimer (DD) | At 14 days after randomization | 
| Proportion of SARS-CoV-2 clearance. | Negativization of RT-PCR for SARS-CoV-2 on nasopharyngeal swab or sputum | At 7 days after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Covid-19, pneumonia, Inflammatory phase, Glucocorticoids