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

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

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.

Study Overview

• Status: Recruiting
• Conditions: covid19
• Intervention / Treatment: Drug: Nitazoxanide; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 380
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • São Paulo
    • Campinas, São Paulo, Brazil
      • Recruiting
      • Hospital Vera Cruz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Informed consent from patient or legal representative.
2. Male or female, aged ≥ 18 years;
3. Laboratory confirmation of 2019-nCoV infection by reverse-transcription polymerase
4. chain reaction (RT-PCR) from any diagnostic sampling source;
5. 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:

1. Participating in another RCT in the past 12 months;
2. Known allergy to nitazoxanide
3. Severely reduced LV function;
4. Severely reduced renal function;
5. Pregnancy or breast feeding;
6. Diagnosis of any other active infection (viral, bacterial, fungal or caused by another pathogen, except the one studied in the trial);
7. History of HIV 1 and/or 2 (Anti-HIV-1,2) and/or HTLV I and II positive;
8. Ongoing antineoplastic treatment with chemotherapy or radiation therapy;
9. Diagnose of severe autoimmune diseases in immunosuppression;
10. Transplanted patients;
11. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: nitazoxanide BID; Patients will receive nitazoxanide 600 mg BID for 7 days.	Drug: Nitazoxanide; Patients will receive nitazoxanide 600 mg BID for 7 days.; Other Names: Viranitta (Nitazoxanide)
Placebo Comparator: Placebo; Patients will receive matching placebo BID for 7 days.	Drug: Placebo; Patients will receive matching placebo BID for 7 days.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Azidus Brasil
• Collaborators: Farmoquimica S.A.
• Investigators: Principal Investigator: Florentino de Araujo Cardoso Filho, MD, PhD, +55 19 991232882

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2022
• Primary Completion (Anticipated): March 1, 2023
• Study Completion (Anticipated): March 1, 2023

Study Registration Dates

• First Submitted: June 8, 2020
• First Submitted That Met QC Criteria: June 8, 2020
• First Posted (Actual): June 9, 2020

Study Record Updates

• Last Update Posted (Actual): October 31, 2022
• Last Update Submitted That Met QC Criteria: October 27, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Anti-Infective Agents; Antiparasitic Agents; Nitazoxanide
• Other Study ID Numbers: NITFQM0920OR-III

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: It is believed that after the data analysis and presentation to the National Commission on Research Ethics, all data of the study will become public.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No