Nitazoxanide Therapy for Patients With COVID-19 Pneumonia

Study Overview
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Brief Summary
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Multicenter, randomized, placebo-controlled, parallel, blinded, interventional, treatment clinical trial with two arms. Population: 500 Hospitalized patients with pneumonia derived from COVID-19 (Coronavirus Disease-19), either confirmed by RT-PCR (Real Time polymerase chain reaction), or suggested by typical findings on the computed tomography scan symptomatic. Experimental group: nitazoxanide 500mg 8 / 8 hours for 5 days. Control group: placebo 8/8 hours for 5 days.

Detailed Description
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SARITA-1 is a multicenter, randomized, placebo-controlled, parallel, blinded, interventional, treatment clinical trial with two arms, which aims to study the impact of nitazoxanide for hospitalized patients with pneumonia derived from COVID-19 (Coronavirus Disease-19) Experimental group: 250 patients received nitazoxanide 500mg 8 / 8 hours for 5 days. Control group: 250 patients received placebo 8/8 hours for 5 days. Population: Patients with clinical symptoms of COVID-19: dyspnoea and/or fever and/or cough) and: either computed tomography scan suggestive of viral pneumonia or confirmatory molecular test by RT-PCR (Real Time polymerase chain reaction),

Official Title
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Nitazoxanide for Moderate to Severe COVID-19 Pneumonia: a Multicenter, Randomized, Placebo-controlled, Double-Blind Clinical Trial

Conditions
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Covid19, Corona Virus Infection, Pneumonia, Viral

Intervention / Treatment
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* Drug: Nitazoxanide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients requiring supplemental oxygen [peripheral oxygen saturation (SpO2) < 93%], admitted to hospital with COVID-19 symptoms associated with chest computed tomography (CT) scan suggestive of viral pneumonia or positive nasopharyngeal swab test for SARS-CoV2 (RT-PCR) Age equal or superior to 18 years Non-pregnant women Willingness to receive study treatment Providing written and informed consent or the same consent signed by a family member Exclusion Criteria: Impossibility to use oral medications History of severe liver disease (Child Pugh C class) Previous renal failure Severe heart failure (NYHA 3 or 4) COPD (GOLD 3 and 4) Neoplasia in the last 5 years Known autoimmune disease Individuals with known hypersensitivity to study drug Previous treatment with the study medication during the last 30 days Clinical suspicion of tuberculosis and bacterial pneumonia

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
Interventional Model Description: Hospitalized patients with clinical signs of COVID-19, and either chest tomography scans suggestive of COVID-19 or confirmed by RT-PCR molecular tests, will be randomly divided into 2 groups: experimental and control groups. Experimental group: 250 hospitalized patients diagnosed with COVID-19 derived pneumonia will receive nitazoxanide 500mg 8/8 hs for 5 days. Control group: 250 hospitalized patients diagnosed with COVID-19 derived pneumonia will receive placebo 8/8 hs for 5 days.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nitazoxanide<br>Patients received nitazoxanide 500mg 8/8hours, for 5 days. | Drug: Nitazoxanide<br>* Nitazoxanide 500mg three times a day for 5 days<br>* Other names: zoxany;|
| Placebo Comparator: Placebo<br>Patients received placebo 500mg 8/8hours, for 5 days | Drug: Placebo<br>* Placebo three times a day for 5 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Orotracheal intubation rate | Compare the intubation rate of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, in the period of 14 days; verified by clinical evolution; quantified by percentage. | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospitalisation days | Compare the number of days patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, stayed at the hospital, in the period of 14 days; verified by clinical evolution; quantified by absolute number. | 14 days | 
| ICU days | Compare the number of days patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, stayed at the ICU, in the period of 14 days; verified by clinical evolution; quantified by absolute number. | 14 days | 
| Intranasal oxygen support days | Compare the number of days patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, stayed with the support of oxygen nasal cannula, in the period of 14 days; verified by clinical evolution; quantified by absolute number. | 14 days | 
| Mortality rate | Compare the mortality rate of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, in the period of 14 days; verified by clinical evolution; quantified by absolute number. | 14 days | 
| Days with fever | Reduction in the duration of fever of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide compared to patients treated with placebo; verified through the collection of clinica data; quantified by the number of days that presented the symptom. | 14 days | 
| Days with cough | Reduction in the duration of cough of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide compared to patients treated with placebo; verified through the collection of clinica data; quantified by the number of days that presented the symptom. | 14 days | 
| Days with dyspnea | Reduction in the duration of dyspnea of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide compared to patients treated with placebo; verified through the collection of clinica data; quantified by the number of days that presented the symptom. | 14 days | 
| Radiologic findings | Compare chest tomographic findings of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide compared to patients treated with placebo; verified through the collection of radiologic data; quantified by the number of patients that presented the a list of alterations. | Day1 | 
| Radiologic findings | Compare chest tomographic findings of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide compared to patients treated with placebo; verified through the collection of radiologic data; quantified by the number of patients that presented the a list of alterations. | Day7 | 
| Cardiologic findings | Compare echocardiographic findings of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide compared to patients treated with placebo; verified through the collection of echocardiographic data; quantified by the number of patients that presented the a list of alterations. | Day1 | 
| Cardiologic findings | Compare echocardiographic findings of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide compared to patients treated with placebo; verified through the collection of echocardiographic data; quantified by the number of patients that presented the a list of alterations. | Day7 | 
| C-reactive protein - absolute number | To evaluate the levels of C-reactive protein (CRP) of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups. | Day 1 | 
| C-reactive protein serum levels | To evaluate the levels of C-reactive protein (CRP) of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups. | Day 3 | 
| C-reactive protein serum levels | To evaluate the levels of C-reactive protein (CRP) of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups. | Day 7 | 
| Lactate dehydrogenase (LDH) serum levels | To evaluate the levels of lactate dehydrogenase (LDH) of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups. | Day 1 | 
| Lactate dehydrogenase (LDH) serum levels | To evaluate the levels of lactate dehydrogenase (LDH) of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups. | Day 3 | 
| Lactate dehydrogenase (LDH) serum levels | To evaluate the levels of lactate dehydrogenase (LDH) of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups. | Day 7 | 
| Troponin serum levels | To evaluate the levels of troponin of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups. | Day 1 | 
| Troponin serum levels | To evaluate the levels of troponin of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups. | Day 3 | 
| Troponin serum levels | To evaluate the levels of troponin of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups. | Day 7 | 
| Electrolytes serum levels | To evaluate the levels of electrolytes of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups. | Day 1 | 
| Electrolytes serum levels | To evaluate the levels of electrolytes of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups. | Day 3 | 
| Electrolytes serum levels | To evaluate the levels of electrolytes of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups. | Day 7 | 
| Glucose serum levels | To evaluate the levels of glucose of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups. | Day 1 | 
| Glucose serum levels | To evaluate the levels of glucose of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups. | Day 3 | 
| Glucose serum levels | To evaluate the levels of glucose of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups. | Day 7 | 
| Renal function | To evaluate renal function of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups. | Day 1 | 
| Renal function | To evaluate renal function of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups. | Day 3 | 
| Renal function | To evaluate renal function of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups. | Day 7 | 
| Coagulogram | To evaluate coagulogram of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups. | Day 1 | 
| Coagulogram | To evaluate coagulogram of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups. | Day 3 | 
| Coagulogram | To evaluate coagulogram of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups. | Day 7 | 
| Liver function panel | To evaluate liver function panel of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups. | Day 1 | 
| Liver function panel | To evaluate liver function panel of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups. | Day 3 | 
| Liver function panel | To evaluate liver function panel of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups. | Day 7 | 
| Ferritin | To evaluate ferritin of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups. | Day 1 | 
| Ferritin | To evaluate ferritin of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups. | Day 3 | 
| Ferritin | To evaluate ferritin of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups. | Day 7 | 
| D-dimer | To evaluate D-dimer of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups. | Day 1 | 
| D-dimer | To evaluate D-dimer of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups. | Day 3 | 
| D-dimer | To evaluate D-dimer of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups. | Day 7 | 
| Blood cell count | To evaluate blood cell count of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, for 7 days; verified by laboratory tests and expressed by the absolute number between the two groups. | 7 days | 
| Inflammatory mediators | To evaluate D-dimer of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups. | Day 1 | 
| Inflammatory mediators | To evaluate D-dimer of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups. | Day 3 | 
| Inflammatory mediators | To evaluate D-dimer of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups. | Day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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brazil, covid19, coronavirus, clinical trial, placebo-controlled, randomized, nitazoxanide, hospitalized patients, covid-19, sars-cov-2, new coronavirus, multicenter, double-blind