Comparison Between Prednisolone and Dexamethasone on Mortality in Patients on Oxygen Therapy, With CoViD-19

Study Overview
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Brief Summary
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The aim of the study is to evaluate two differents regimens of corticosteroids (prednisolone versus dexamethasone) on D28 mortality in patients with CoViD 19 pneumonia requiring oxygen supplementation

Detailed Description
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Low-dose glucocorticoid treatment is the only medication showing a significant reduction in mortality in cases of COVID-19 pneumonia requiring oxygen supplementation or ventilatory support. Intravenous or oral dexamethasone are well evaluated in randomized study but other oral corticosteroids are not. Compared to dexamethasone, prednisolone is more available in France and easily taken by patients, especially in case of home medical care. The pharmacokinetics/pharmacodynamics of prednisolone and dexamethasone are different. To obtain similar effects, prednisolone should be theoretically taken twice a day and at a superior dose than the strict prednisone equivalence of 6mg dexamethasone.

Official Title
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Comparison Between Prednisolone and Dexamethasone on D28 Mortality in Patients on Oxygen Therapy, With CoViD-19: Multicenter, Randomized, Open-label Non-inferiority Study

Conditions
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Coronavirus Infection

Intervention / Treatment
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* Drug: DEXAMETHASONE
* Drug: PREDNISOLONE


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient ≥ 18 years old Patient with SARS-CoV-2 pneumopathy documented by nasopharyngeal or bronchoalveolar lavage fluid RT-PCR or any documented clinical symptoms support by CT scan Patient with SpaO2 ≤ 94 % in room air (90% for patient with respiratory failure) and requiring an oxygen therapy Negative pregnancy test for women of childbearing age Informed and written informed consent (IC) obtained Patients with affiliation to the social security system Exclusion Criteria: Patient with corticosteroids as background treatment (≥ 10 mg equivalent) Patient under supplemental oxygen > 6 L/min Immunocompromised patient (AIDS, bone marrow or solid organ transplants, etc.) Patient who received a corticosteroid dose within 3 days for Covid-19 Medical history of hypersensitivity to Prednisolone or Dexamethasone; or lactose / galactose (excipients with known effect) Another active virus such hepatitis, herpes, varicella, shingles …. Psychotic state not controlled by treatment

Ages Eligible for Study
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Minimum Age: 18 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: DEXAMETHASONE Arm<br>Patients will take 6 mg per day of Dexamethasone during 10 days | Drug: DEXAMETHASONE<br>* Patients will take 60 mg per day of Prednisolone (40 mg morning and 20 md evening) between D1 to D10<br>* Other names: DEXAMETHASONE Arm;|
| Active Comparator: PREDNISOLONE Arm<br>Patients will take 60 mg per day of Prednisolone during 10 days | Drug: PREDNISOLONE<br>* Patients will take 60 mg per day of Prednisolone (40 mg morning and 20 md evening) between D1 to D10<br>* Other names: PREDNISOLONE Arm;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality assessment at D28 | Assessment of vital status at D28 in Dexamethason arms vs Prednisolone arms | At Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of clinical course in both groups (arms) | The clinical course for each patient will be measured, for several items, and compared between both groups to see if a significant difference is observed. Items, considered for comparison, are listed below : Number of oxygen therapy days, Number of patients requiring oxygen therapy increase (High-Flow Oxygen Therapy, CPAP/BIPAP, mechanical ventilation, ECMO) Number of hospital days Number of patient admitted in Resuscitation Unit /Intensive care Unit Number of patient with organic damage other than lung Number of disease-related infection other than SARS-Cov-2 Frequency and evolution of complication of corticosteroid therapy (Severity evaluated according to CTCAE (diabetes, acute psychosis or other adverse effect consider to be link to corticosteroide therapy by investigator)) | At Day 28 | 
| Measurement of evolution of respiratory symptoms in both groups (arms) | Evolution of respiratory symptoms will be measured for each patient, for several items, and compared between both groups to see if a significant difference is observed. Items, considered for comparison, are listed below : Oxygen saturation rate, Oxygen flow, Respiratory rate | From Day 0 to Day 28 | 
| Assessment of patient satisfaction towards the treatment | Assessment of patient satisfaction with a satisfaction questionnaire (Likert-type scale) For each item, patient ticks : Very satisfied, Satisfied, Unsatisfied or Very unsatisfied | At Day 28 | 
| Comparison betwween D1 and D28 of patient quality of life evolution between randomization groups (arms) | Measurement of patient quality of life evolution with EQ5D self-assessment questionnaire at day1 and day 28. For item of mobility, autonomy and current activities, patient ticks : I have no problem, I have some problems or I am I am unable to do For item of pain and anxiety/depression, patient ticks : no, moderate or severe | At Day 1 and Day 28 | 
| Comparison betwween D1 and D28 of adverse events and adverse effects between randomization groups (arms) | Measurement of adverse events number and adverse effects number during the 28 days of the study | At Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Coronavirus Infections, SARS-CoV-2, Corticostéroïdes, Severe form of COVID-19