Hydroxychloroquine vs Nitazoxanide in Patients With COVID-19

Study Overview
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Brief Summary
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Coronaviruses (CoV) are positive-sense single-stranded RNA viruses that infect a wide range of hosts producing diseases ranging from the common cold to serious / fatal events. Nitazoxanide (NTZx) is a derivative of 5-nitrothiazole, synthesized in 1974 by Rosignol - Cavier. NTZx has powerful antiviral effects through the phosphorylation of protein kinase activated by double-stranded RNA, which leads to an increase in phosphorylated factor 2-alpha, an intracellular protein with antiviral effects. The purpose of this study is to contrast the beneficial effect of NTZx vs NTZx plus hydroxychloroquine in patients Coronavirus Disease (COVID-19) as well as against other treatments.

Detailed Description
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Introduction The current pandemic caused by the SARS-COV2 coronavirus (COVID-19) is life-threatening and is challenging the world's best health systems. Accelerated spread of this pandemia led physicians to try a variety of treatments without a well established sequence due to ignorance about this new disease. The case fatality rate has been calculated at 2.2% but there are differences depending on the country affected. Perspective When comparing the evolution of cases between Spain and Mexico, an apparently less pronounced trend is observed in Mexico, but this may be due to underdiagnosis. In calculations by the Mexican Ministry of Health, around 6% of the patients (approximately 10,500) who contract COVID-19 could be found serious and in need of hospitalization in intensive care. NTZx NTZx and its circulating active metabolite, tizoxanide, inhibit the replication of a wide range of viruses, both RNA and DNA. It has action against 16 strains of Influenza A virus subtypes H1N1, H3N2, H3N2v, H3N8, H5N9, H7N1 and a strain of influenza B. It also works against respiratory syncytial virus, norovirus, dengue, yellow fever, Japanese encephalitis virus, rotavirus , hepatitis B and C, even against the human immunodeficiency virus (Severe Acute Respiratory Syndrome (SARS) and Middle East respiratory syndrome (MERS). Problem Mexico is in Phase 2 according to the World Health Organization (WHO) and more local infections due to coronaviruses are expected. To date, various COVID-19 treatment schemes are being tested, but the usefulness of none can be assured. When reviewing the drug schemes that are being carried out in the world, it calls the attention that developing countries are not included, beyond the fact that the tested alternatives are economically inaccessible. This clinical survey aims to test the possible utility of NTZx against COVID-19, alone or in combination with hydroxychloroquine.

Official Title
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Treatment With Hydroxychloroquine vs Nitazoxanide + Hydroxychloroquine in Patients With COVID-19 With Risk Factors for Poor Outcome

Conditions
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Coronavirus Infection

Intervention / Treatment
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* Drug: Nitazoxanide 500 MG
* Drug: Hydroxychloroquine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: COVID-19 positive patients Treated at the Health Institute of the State of Mexico (ISEM). With risk factors to get complicated: age more than 60 years old, diabetes mellitus or obesity grade II or more. Exclusion Criteria: Patients who have inherent contraindications to each drug.

Ages Eligible for Study
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Minimum Age: 5 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: In this study all patients with a COVID-19 positive result attended at the Health Institute of the State of Mexico (ISEM), will be invited to participate and offered one of two options that try to reduce the complications of this disease.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nitazoxanide + hydroxychloroquine<br>Hydroxychloroquine 400 mg PO every 12 hours for two days and then 200 mg PO every 12 hours for four days + Nitazoxanide 500 mg PO every 6 hours for six days | Drug: Nitazoxanide 500 MG<br>* Clinical evaluation of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using this option with two drugs<br>* Other names: hydroxychloroquine;Drug: Hydroxychloroquine<br>* Clinical evaluation of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using this option with one drug<br>|
| Active Comparator: Hydroxychloroquine<br>Hydroxychloroquine 200 mg PO every 12 hours for 7 days | Drug: Hydroxychloroquine<br>* Clinical evaluation of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using this option with one drug<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mechanical ventilation requirement | Percentage of patients COVID-19 positive that required mechanical ventilation | Since the diagnosis until two weeks after | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treatment, Evolution