Efficacy and Safety of Nitazoxanide 600 mg BID Versus Placebo for the Treatment of Hospitalized Patients With COVID-19

Study Overview
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Brief Summary
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This is a pivotal phase III study to evaluate the efficacy of nitazoxanide 600 mg BID compared to placebo to treat hospitalized patients with non-critical COVID-19.

Detailed Description
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This is pivotal phase III study to evaluate the efficacy of nitazoxanide 600 mg BID compared to placebo to treat hospitalized patients with non-critical COVID-19. The aim is to demonstrate a decrease in hospital related complications among patients who are hospitalized with moderate COVID-19 by treating them with nitazoxanide BID 600 mg for 7 days on top of standard care compared to placebo on top of standar care.. Therefore, patients hospitalized with confirmed diagnosis of COVID-19 will be randomized to receive either nitazoxanide 600 mg BID or Placebo.

Official Title
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A Phase III, Multicentre, Parallel, Randomized, Double-blind Clinical Trial to Assess the Efficacy and Safety of Nitazoxanide 600 mg Compared to Placebo in the Treatment of Hospitalized Patients With COVID-19 in Non-critical Condition

Conditions
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covid19

Intervention / Treatment
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* Drug: Nitazoxanide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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; Hospitalized for up to 48h with signs of respiratory failure with or without non-invasive ventilation and i. Oxygen saturation <98%; 7. Negative result for pregnancy test (if applicable). Exclusion Criteria: Participating in another RCT in the past 12 months; Known allergy to nitazoxanide Severely reduced LV function; Severely reduced renal function; Pregnancy or breast feeding; Diagnosis of any other active infection (viral, bacterial, fungal or caused by another pathogen, except the one studied in the trial); History of HIV 1 and/or 2 (Anti-HIV-1,2) and/or HTLV I and II positive; Ongoing antineoplastic treatment with chemotherapy or radiation therapy; Diagnose of severe autoimmune diseases in immunosuppression; Transplanted patients; 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
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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: Patients will be randomized to receive either nitazoxanide 600 mg BID or Placebo (1:1)
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: nitazoxanide BID<br>Patients will receive nitazoxanide 600 mg BID for 7 days. | Drug: Nitazoxanide<br>* Patients will receive nitazoxanide 600 mg BID for 7 days.<br>* Other names: Viranitta (Nitazoxanide);|
| Placebo Comparator: Placebo<br>Patients will receive matching placebo BID for 7 days. | Drug: Placebo<br>* Patients will receive matching placebo BID for 7 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Need of mechanical ventilation | Evaluation of change in acute respiratory syndrome using WHO Ordinal Scale for Clinical Improvement that measures illness severity over time (0=uninfected; ambulatory, no limitation of activities=1; ambulatory, limitation of activities=2, hospitalized no oxygen therapy=3; hospitalized oxygen by mask or nasal prongs=4; hospitalized non invasive ventilation or high-flow oxygen=5; hospitalized intubation or mechanical ventilation=6; hospitalized ventilation + additional organ support=7; death=8) | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the pulmonary condition | Evaluation of change in oximetry, respiratory rate and need for oxygen therapy | Baseline, Day 7 and Day 14 | 
| Change in Clinical Condition | Evaluation of change in the following symptoms: cough, headache, myalgia and fever, level of consciousness and organ dysfunction | Baseline, Day 7 and Day 14 | 
| Change in tomographic pulmonary condition | Evaluation of change in chest CT | Baseline, Day 7 | 
| Rate of mortality within 14-days | Evaluation of change in acute respiratory syndrome | 14 days | 
| Change in inflammatory markers | Evaluation of change in inflammatory markers d-dimer and IL-6 | Baseine, Day 7, Day 14 |