Evaluation of the Efficacy and Safety of Treatments for Patients Hospitalized for COVID-19 Infection Without Signs of Acute Respiratory Failure, in Tunisia

Study Overview
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Brief Summary
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Evaluation of the efficacy and safety of Treatments for Patients Hospitalized for COVID-19 Infection without signs of acute respiratory failure, in Tunisia Multicentric Randomized Comparative Study

Detailed Description
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Arm 1: Hydroxychloroquine (HCQ): 600 mg on the 1st day as a starting dose then 200 mg * 2 /D for 9 days Azithromycin: 500 mg (1st day) then 250 mg / D for 4 days Usual standard treatment Arm 2: HCQ: 600 mg on the 1st day as a starting dose then 200 mg * 2 / D for 9 days Azithromycin: 500 mg (1st day) then 250 mg / D for 4 days Zinc: 220 mg per day for 10 days Usual standard treatment Arm 3: Azithromycin: 500 mg (1st day) then 250 mg / D for 4 days Doxycycline: 200 mg per day for 10 days. Usual standard treatment

Official Title
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Evaluation of the Efficacy and Safety of Treatments for Patients Hospitalized for COVID-19 Infection Without Signs of Acute Respiratory Failure, in Tunisia Multicentric Randomized Comparative Study

Conditions
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COVID 19, Patients Hospitalized

Intervention / Treatment
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* Drug: HCQ
* Drug: Azithromycin
* Drug: Doxycycline
* Dietary Supplement: Zinc


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed patient COVID19 positive with clinical signs of acute lower respiratory infection with signs of pneumonia or bronchitis: fever and / or cough and / or difficulty breathing in the absence of acute respiratory failure (PaO2> 60 mmHg) with Plus or less : Chills Asthenia, fatigability Headache Arthromas myalgia Dry throat Rhinorrhea An anosmia chest pain Diarrhea Nausea and vomiting Absence of rhythm disturbance (Qt interval <500ms) Patients hospitalized in the medical service 18 years old <Age <80 years old Having given written consent for their participation in the study Exclusion Criteria: Allergy to macrolides, local anesthetics such as lidocaine or amide type and betalactamines Take hydroxychloquine in the previous month Severe / severe liver failure Kidney failure (GFR <30 ml / min / 1.73 m2) Ongoing treatments with colchicine, ergot, rye, pimozide, mizolastine, simvastatin, lomitapide, alfuzosin, dapoxetine, avanafil, ivabradine, eplerenone, dronedarone, quetiapine, ticagrelor, cisapride, astemizole, terfenadine, ranolazine, domperidone. Complete branch block Hypovolemia Retinopathy including vitreous involvement Psoriasis Pregnant or breastfeeding woman hypersensitivity to chloroquine or hydroxychloroquine or to any of the other ingredients of this medication

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Interventional Model Description: Parallel assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HCQ+Azithromycin<br>Hydroxychloroquine (HCQ): 600 mg on the 1st day as a starting dose then 200 mg * 2 / D for 9 days Azithromycin: 500 mg (1st day) then 250 mg / D for 4 days Usual standard treatment | Drug: HCQ<br>* 600 mg on the 1st day as a starting dose then 200 mg * 2 /D for 9 days<br>Drug: Azithromycin<br>* 500 mg (1st day) then 250 mg / D for 4 days<br>|
| Experimental: HCQ+Azithromycin+Zinc<br>HCQ: 600 mg on the 1st day as a starting dose then 200 mg * 2 / D for 9 days Azithromycin: 500 mg (1st day) then 250 mg / D for 4 days Zinc: 220 mg per day for 10 days Usual standard treatment | Drug: HCQ<br>* 600 mg on the 1st day as a starting dose then 200 mg * 2 /D for 9 days<br>Drug: Azithromycin<br>* 500 mg (1st day) then 250 mg / D for 4 days<br>Dietary Supplement: Zinc<br>* 220 mg per day for 10 days<br>|
| Experimental: Azithromycin+Doxycycline<br>Azithromycin: 500 mg (1st day) then 250 mg / D for 4 days Doxycycline: 200 mg per day for 10 days. Usual standard treatment | Drug: Azithromycin<br>* 500 mg (1st day) then 250 mg / D for 4 days<br>Drug: Doxycycline<br>* 200 mg per day for 10 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the rate of patients cured at the end of the study. | The healing criteria are defined clinically as: disappearance of clinical signs of acute respiratory infection absence of fever | 2 months | 
| Evaluate the rate of patients are pauci-symptomatic at the end of the study. | A patient will be defined as pauci-symptomatic if presence: Light dry cough Discomfort, More or less : Headache, Muscle pain | 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the rate of patients with worsening clinical signs | Patients require transfer to intensive care with the appearance of: Acute respiratory failure: PaO2 <60 mmHg in AA gold Signs of circulatory insufficiency: mottling, tachycardia, systolic BP ≤90mmHg or having dropped by 40 mmHg compared to base BP or Confusion or alteration of the state of consciousness | 2 months |