Efficacy and Safety of Hydroxychloroquine and Azithromycin for Patients With Moderate to Severe COVID-19

Study Overview
=================
Brief Summary
-----------------
This is an exploratory study to evaluate the efficacy of hydroxychloroquine (400 mg BID on D1 and 400 mg/day on D2 to D5) and azithromycin (500 mg/ 5 days) to treat moderate to severe COVID-19 pneumonia.

Detailed Description
-----------------
This is an exploratory, open label, multi-center study to evaluate the efficacy of hydroxychloroquine (HCQ) (400 mg BID on D1 and 400 mg/day on D2 to D5) and azithromycin (AZT) (500 mg/ 5 days) to treat moderate to severe COVID-19 pneumonia. We aim to demonstrate decrease in hospital related complications among patients who are hospitalized with moderate or severe COVID-19 by treating them with HCQ and AZT on top of standard care compared to patients who receive standard care only. Patients hospitalized with confirmed diagnosis of COVID-19 will receive the treatment. Patients that do not fulfill the inclusion/exclusion criteria or that is not willing to participate in the study will be invited to consent the use of their data as part of a control group.

Official Title
-----------------
Open, Multicentric, Non Randomized, Exploratory Clinical Trial to Assess the Efficacy and Safety of Hydroxychloroquine and Azithromycin for the Treatment of Acute Respiratory Syndrome (COVID-19) Caused by SARS-CoV-2 Virus

Conditions
-----------------
COVID-19

Intervention / Treatment
-----------------
* Drug: Hydroxychloroquine Sulfate
* Drug: Azithromycin Tablets


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Informed consent from patient or legal representative. Male or female, aged ≥ 18 years; Laboratory confirmation of 2019-nCoV infection by reverse-transcription polymerase chain reaction (RT-PCR) from any diagnostic sampling source; At least one of the characteristic symptoms of COVID-19 Hospitalized for up to 36h with non-invasive ventilation or up to 24h with invasive ventilation. Negative result for pregnancy test (if applicable). Exclusion Criteria: Participating in another RCT in the past 12 months; Known allergy to HCQ or chloroquine Any contraindication to HTC or AZT, including retinopathy and prolonged QT, Severely reduced LV function Severely reduced renal function; Pregnancy or breast feeding Any other clinical condition which, in the opinion of the principal investigator, would not allow safe completion of the protocol and safe administration of the investigational products

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: All patients included in the study will receive hydroxychloroquine (HCQ) 400 mg (BID/ 7 days) and azithromycin (AZT) (500 mg/ 5 days) on top of standard care. Patients that do not consent to participate or that do not fulfill eligibility criteria will be invited to participate as control group and will receive standard care only.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HCQ + AZT<br>All patients included in the study will receive HCQ (400 mg BID on D1 and 400 mg/day on D2 to D5) and AZT (500 mg/ 5 days) on top of standard care. | Drug: Hydroxychloroquine Sulfate<br>* All patients included in the study will receive HCQ (400 mg BID on D1 and 400 mg/day on D2 to D5) for 5 days.<br>* Other names: Reuquinol;Drug: Azithromycin Tablets<br>* All patients included in the study will receive AZT 500 mg per day for 5 days.<br>* Other names: Azithromycin;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evolution of acute respiratory syndrome, oxygen saturation hemodynamic stability | Evaluation of change from baseline. Kaplan-meier method will be used. | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Viral load | Evaluation of change in viral load | Day 6 | 
| Change in Clinical Condition | Time for normalization of body temperature, respiratory rate and cough relief | 28 days | 
| Evolution of Acute Respiratory Syndrome | Time to wean off oxygen supplementation and / or invasive / non-invasive ventilatory support; | 28 days | 
| Hospital discharge | Time to be discharged from hospital | 28 days | 
| Rate of mortality within 28-days | Evaluation of change in acute respiratory syndrome | 28 days |