Hydroxychloroquine, Azithromycin in the Treatment of Covid-19

Study Overview
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Brief Summary
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This study investigates the efficay and tolerance of 5-days course of hydroxychloroquine or hydroxychloroquine and azithromycin of patients with COVID-19 infection. The investigators will undertake a randomized, double-blind, controlled Trial in the region of Sousse Tunisia

Detailed Description
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There is a critical need to identify effective treatments and a number of molecules have been suggested, but The investigators still do not have enough evidence about their efficacy, to treat COVID-19 pneumonia. One of the most tested treatments was the use of Chloroquine or Hydroxychloroquine associated or not to azithromycin. Studies have indicated that chloroquine (CQ) shows antagonism against COVID-19 in vitro. It's known to block virus infection by increasing endosomal pH required for virus/cell fusion, as well as interfering with the glycosylation of cellular receptors of SARS-CoV. It's also demonstrated that CQ functioned at both entry, and at postentry stages of the 2019-nCoV infection in Vero E6 cells. Besides its antiviral activity, CQ has an immune-modulating activity, which may synergistically enhance its antiviral effect in vivo. However, evidence regarding its effects in patients is limited. Among patients with COVID-19, the use of Hydroxychloroquine (HCQ) could significantly shorten time to clinical recovery (TTCR) and promote the absorption of pneumonia. This result has been presented in a randomized controlled trial using two arms HCQ versus conventional treatment. The beneficial effect of HCQ has been proven among mild severity COVID-19 pneumonia but the sample size of this study was limited to 31 patients in each group. Gautret et al also reported that HCQ treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin. A study showed that azithromycin concentration in phagocytic cells is 40× to 150× higher than plasma concentrations. However, Gautret study has many limitations including selection biases because of non-randomization, a small sample size, and dropout of six patients from the study. In terms of treatment duration, there is no study supporting a long course treatment of 10 days versus a short course treatment of 5 days for HCQ. This treatment is known to have a large distribution volume of 73 l/kg and a plasma half life going from 22 days to 123 days. This suggests that a short course treatment of Hydroxychloroquine and/or azithromycin could be as effective as a long course treatment. On the other hand, there are currently no effective specific antivirals or drug combinations supported by high-level evidence, and The investigators don't know if HCQ could be effective or if it's effectiveness may be improved if it's associated with Azithromycin. In fact, this association can lead to improve pneumonia but can also increase the risk of treatment side effects.

Official Title
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Hydroxychloroquine, Azithromycin in the Treatment of Covid-19 Pneumonia: A Randomized,Open-label,Controlled Clinical Trial

Conditions
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SARS-CoV-2 Pneumonia, COVID-19

Intervention / Treatment
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* Drug: Hydroxychloroquine 200 Mg Oral Tablet
* Drug: Azithromycin 250 MG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: PositiveSARS-COV-2 RT-PCR in hospitalized patients in University Hospital Farhat Hached in Sousse Tunisia. Had either not received hydroxychloroquine before or had received hydroxychloroquine for at least 1 day and could tolerate a dose of 200 mg of hydroxychloroquine/day. Exclusion Criteria: Unableto take oral medication, pregnancy or breast feeding, immune-compromised patients, Contraindicationto the studied medications

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hydroxychloroquine associated to azithromycin<br>Hydroxychloroquine: 200 mg twice a day orally or via gastric tube (total 400 mg/day) for 5 days. Azithromycin: 500 mg at day 1 then 250 mg/day for 4 days. with standard of care in association to treatments. | Drug: Hydroxychloroquine 200 Mg Oral Tablet<br>* orally or via gastric tube<br>* Other names: Plaquenil;Drug: Azithromycin 250 MG<br>* orally or via gastric tube<br>* Other names: Azro 250;|
| Active Comparator: Hydroxychloroquine with placebo<br>Hydroxychloroquine: 200 mg twice a day orally or via gastric tube (total 400 mg/day) for 5 days. with standard of care in association to treatments. | Drug: Hydroxychloroquine 200 Mg Oral Tablet<br>* orally or via gastric tube<br>* Other names: Plaquenil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical recovery at day-14, from the start of treatment. | Clinical recovery is defined as a complete resolution clinical signs appeared during the medical history and related to COVID-19. | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Viral Clearance via RT-PCR at day 5- 7-10 and day 14 | RT-PCR will be realized in same laboratory | 5- 7-10 and day 14 |