Protective Role of Inhaled Steroids for Covid-19 Infection

Study Overview
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Brief Summary
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We hypothesize that inhaled steroid therapy and long acting beta 2 adrenergic agonist, widely prescribed in asthma patients, may also have a local protective effect against coronavirus infection, even in patients without asthma. The primary purpose is To compare time to clinical improvement in patients receiving standard of care associated to the combination budesonide/formoterol or standard of care only. Time (in days) to clinical improvement is defined as the time from randomization to an improvement of two points (from the status at randomization) on a seven-category ordinal scale or live discharge from the hospital, whichever came first within 30 days.

Detailed Description
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D1 inclusion / randomization visit: Patients who meet the eligibility criteria and whose infection with Covid-19 has been confirmed within 48 hours will be included in the respiratory diseases department by the pneumologist investigator. Patients will be randomized either to the control group or to the intervention group. For interventional patients, trial treatment (SYMBICORT RAPIHALER 200/6 µ) will begin within 12 hours. Follow-up period (D2 to D29) and end of study visit (D30): Throughout their hospital stay, patients will be followed in accordance with the practice of the service. During hospitalization, investigators are free to decide for antibiotics, steroids, anti viral drugs, hydroxychloroquine and oxygen support management in accordance with local practice. None of the laboratory tests are made for the study. They are usually performed in patients hospitalized for acute respiratory infection. Interventional patient will also be treated with SYMBICORT RAPIHALER 200/6 µg (2 puffs 2 times a day). In the event that the patient is discharged from hospital before the end of his participation, he will be contacted by phone on D30 in order to obtain information concerning the period outside hospitalization

Official Title
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Protective Role of Inhaled Steroids for Covid-19 Infection

Conditions
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Covid-19 Infection, Hospitalization in Respiratory Disease Department

Intervention / Treatment
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* Drug: 2: Usual practice + SYMBICORT RAPIHALER
* Other: 1: Usual practice


Participation Criteria
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Eligibility Criteria
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Inclusion criera : Patient ≥ 18 years old and ≤ 75 years old Laboratory proved infection by COVID-19 by RT-PCR on a respiratory biological sample within 2 days Hospitalization is required according to current local recommendations Patient affiliated to a social security regime Patient able to give free, informed and written consent Exclusion criteria : Oxygen flow rate >8l/min at inclusion Current treatment with any inhaled steroid (any other form of steroid administration does not exclude the patient) Intensive care unit is required for the patient (based on investigator judgement) Patient with cognitive impairment which do not guarantee proper use of the treatment by the patient himself Pregnant (positive β-HCG at inclusion) or breastfeeding women Participation in another interventional drug study involving human participants and concerning COVID-19 infection or being in the exclusion period of a previous study involving human participants Contraindications to the treatments (history of hypersensitivity) Patient admitted for isolation, for social reason or due to comorbidities without gravity sign Long-term patient treated with digitalis, disopyramide, procainamide or phenothiazine that could lengthen the QT space

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1: Usual practice<br>arm will be follow during 30 days | Other: 1: Usual practice<br>* Usual practice<br>|
| Experimental: 2: Usual practice + SYMBICORT RAPIHALER<br>Usual practice + SYMBICORT RAPIHALER 200/6 µg ( 2 puffs bid during 30 days) | Drug: 2: Usual practice + SYMBICORT RAPIHALER<br>* 2 puffs bid during 30 days by inhalation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time (in days) to clinical improvement within 30 days after randomization | Time (in days) to clinical improvement is defined as the time from randomization to an improvement of two points (from the status at randomization) on a seven-category ordinal scale or live discharge from the hospital, whichever came first within 30 days. The seven-category ordinal scale consisted of the following categories: Not hospitalized with resumption of normal activities Not hospitalized, but unable to resume normal activities Hospitalized, not requiring supplemental oxygen Hospitalized, requiring supplemental oxygen Hospitalized, requiring nasal high-flow oxygen therapy, non-invasive mechanical ventilation, or both; Hospitalized, requiring ECMO, invasive mechanical ventilation, or both Death. These parameters will be evaluated daily during hospitalization. | within 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality rate at D30 |  | At day30 | 
| Time (in days) from randomization to death |  | up to 30 days after randomization | 
| Number of days alive outside ICU within 30 days |  | At day30 | 
| Number of days alive free of invasive or non-invasive ventilation within 30 days |  | At day30 | 
| Number of days alive with oxygen therapy within 30 days |  | At day30 | 
| Maximal oxygen rate within 30 days |  | At day30 | 
| Difference between PaO2/FiO2 ratio at randomization and at Day 7 (or at the time of stopping oxygen therapy or discharge if occurs before Day 7) |  | at Day 7 | 
| Number of days alive outside hospital within 30 days |  | at Day 30 | 
| Use of antibiotics for respiratory (proved or suspected) infection within 30 days |  | at Day 30 | 
| Difference between CRP levels at randomization and at Day 7 (or at the time of discharge if occurs before Day 7) |  | at Day 7 | 
| Safety outcomes included events that occurred during treatment, serious adverse events, and premature discontinuation of treatment. |  | up to 30 days after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Covid-19, Asthma, Inhaled steroids, Formoterol, Oxygen