Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Effects of Early Use of Nitazoxanide in Patients With COVID-19

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04552483
Recruitment Status : Completed
First Posted : September 17, 2020
Last Update Posted : November 3, 2020
Sponsor:
Collaborators:
Ministry of Science and Technology, Brazil
National Research Council, Brazil
ATCGen
Complexo Hospitalar Municipal de São Caetano do Sul
Hospital de Transplante Doutor Euryclides de Jesus Zerbini
Secretaria Municipal de Saúde de Bauru
Santa Casa de Misericórdia de Sorocaba
Secretaria Municipal de Saúde de Guarulhos
Hospital e Maternidade Therezinha de Jesus
Secretaria de Estado de Saúde do Distrito Federal
Information provided by (Responsible Party):
Jose Roberto Lapa e Silva, Universidade Federal do Rio de Janeiro

Brief Summary:

Multicenter, randomized, placebo-controlled, parallel, blinded, interventional, treatment clinical trial with two arms.

Population: 392 Patients with COVID-19 (Coronavirus Disease-19), confirmed by RT-PCR (Real Time polymerase chain reaction), symptomatic in the early phase of the disease.

Experimental group: 196 patients, nitazoxanide 500mg 8 / 8 hours for 5 days. Control group: 196 patients, placebo 8/8 hours for 5 days.


Condition or disease Intervention/treatment Phase
Covid19 Coronavirus Drug: Nitazoxanide Drug: Placebo Phase 2

Detailed Description:

SARITA-2 is a multicenter, randomized, placebo-controlled, parallel, -blinded, interventional, treatment clinical trial with two arms, which aims to study the impact of nitazoxanide in the early phase of the COVID-19 (Coronavirus Disease-19).

Experimental group: 196 patients received nitazoxanide 500mg 8 / 8 hours for 5 days. Control group: 196 patients received placebo 8/8 hours for 5 days.

Population: 392 Patients with COVID-19, confirmed by RT-PCR (Real Time polymerase chain reaction), symptomatic in the early phase of the disease.

Calculation of the sample size was based on a previous study which demonstrated that 78% of Covid-19 patients in group 4 (Hospitalized without oxygen therapy), according to the WHO ordinal classification, experienced complete resolution of symptoms after receiving placebo.10 In the present trial, patients were classified as group 2 (Symptomatic and independent), and a greater degree of recovery as measured by symptom-free days (80%) was expected even after placebo. Thus, assuming an 11% increase in symptom-free days in those patients who would receive nitazoxanide compared to placebo, we would need approximately 196 patients per experimental group, admitting a beta error of 15% and alpha error of 5%, for a total n of 392 patients. Calculation of the sample size was done by G*Power 3.1.9.2 (Universität Düsseldorf, Düsseldorf, Germany).

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 392 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Patients diagnosed with COVID-19 will be randomly divided into 2 groups: experimental and control groups.

Experimental group: 196 patients diagnosed with COVID-19 confirmed by RT-PCR will receive nitazoxanide 500mg 8/8 hs for 5 days. Control group: 196 patients diagnosed with COVID-19 confirmed by RT-PCR will receive placebo 8/8 hs for 5 days.

Masking: Double (Participant, Care Provider)
Masking Description: Patients were randomly allocated into one of the two groups: A or B. Patients received labelled medication: A or B, by the pharmacist. Patients received an identification number, so care providers, outcomes assessors and investigators did not know anything regarding the patients' groups.
Primary Purpose: Treatment
Official Title: Effects of Nitazoxanide Administration to Patients in the Initial Phase of COVID-19
Actual Study Start Date : June 8, 2020
Actual Primary Completion Date : August 20, 2020
Actual Study Completion Date : September 5, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Nitazoxanide
Patients received nitazoxanide 500mg 8/8hours, for 5 days.
Drug: Nitazoxanide
Nitazoxanide 500mg 8/8 hours for 5 days in the early clinical phase of COVID-19.
Other Names:
  • azox
  • annita
  • irose
  • tanisea
  • trinida
  • zoxany

Placebo Comparator: Placebo
Patients received placebo 500mg 8/8hours, for 5 days.
Drug: Placebo
Placebo 8/8 hours for 5 days in the early clinical phase of COVID-19.




Primary Outcome Measures :
  1. Days with fever [ Time Frame: Day8 ]
    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 information with the patient; quantified by the number of days that presented the symptom.

  2. Days with cough [ Time Frame: Day8 ]
    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 information with the patient; quantified by the number of days that presented the symptom.

  3. Days with asthenia [ Time Frame: Day8 ]
    Reduction in the duration of asthenia of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide compared to patients treated with placebo; verified through the collection of information with the patient; quantified by the number of days that presented the symptom.


Secondary Outcome Measures :
  1. SARS-COV-2 viral load - absolute number [ Time Frame: Day1 ]
    Compare the evolution of viral load in naso- and oropharyngeal swab in patients with COVID-19 treated with nitazoxanide or placebo on day 1; verified using the RT-PCR technique; quantified by the absolute number

  2. SARS-COV-2 viral load - absolute number [ Time Frame: Day8 ]
    Compare the evolution of viral load in naso- and oropharyngeal swab in patients with COVID-19 treated with nitazoxanide or placebo on day 8; verified using the RT-PCR technique; quantified by the absolute number.

  3. SARS-COV-2 viral load - percentage [ Time Frame: Day 1 ]
    Compare the evolution of viral load in naso- and oropharyngeal swab in patients with COVID-19 treated with nitazoxanide or placebo on day 1; verified using the RT-PCR technique; quantified by the percentage change between the two groups.

  4. SARS-COV-2 viral load - percentage [ Time Frame: Day 8 ]
    Compare the evolution of viral load in naso- and oropharyngeal swab in patients with COVID-19 treated with nitazoxanide or placebo on day 8; verified using the RT-PCR technique; quantified by the percentage change between the two groups.

  5. Hospital admission rate - absolute number [ Time Frame: Day8 ]
    Compare the hospital admission 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 8 days; verified by information actively collected from patients or family members; quantified by absolute number.

  6. Hospital admission rate - percentage [ Time Frame: Day8 ]
    Compare the hospital admission 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 8 days; verified by information actively collected from patients or family members; quantified by percentage.

  7. Serum Interleukin-6 [ Time Frame: Day 3 ]
    Compare the levels of inflammatory mediators: (interleukin [IL] -6 from patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by the measurement of cytokines in patient serum by the ELISA technique; quantified by the absolute number between the two groups.

  8. Serum Interleukin-6 [ Time Frame: Day 8 ]
    Compare the levels of inflammatory mediators: (interleukin [IL] -6 from patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 8; verified by the measurement of cytokines in patient serum by the ELISA technique; quantified by the absolute number between the two groups.

  9. Serum Interleukin-1-beta [ Time Frame: Day 3 ]
    Compare the levels of inflammatory mediators: IL-1-beta from patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by the measurement of cytokines in patient serum by the ELISA technique; quantified by the absolute number between the two groups.

  10. Serum Interleukin-1-beta [ Time Frame: Day 8 ]
    Compare the levels of inflammatory mediators: IL-1-beta from patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 8; verified by the measurement of cytokines in patient serum by the ELISA technique; quantified by the absolute number between the two groups.

  11. Serum Interleukin-8 [ Time Frame: Day 3 ]
    Compare the levels of inflammatory mediators: IL-8 from patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by the measurement of cytokines in patient serum by the ELISA technique; quantified by the absolute number between the two groups.

  12. Serum Interleukin-8 [ Time Frame: Day 8 ]
    Compare the levels of inflammatory mediators: IL-8 from patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 8; verified by the measurement of cytokines in patient serum by the ELISA technique; quantified by the absolute number between the two groups.

  13. Serum tumor necrosis factor (TNF)-alfa [ Time Frame: Day 3 ]
    Compare the levels of inflammatory mediators: tumor necrosis factor (TNF)-alfa from patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by the measurement of cytokines in patient serum by the ELISA technique; quantified by the absolute number between the two groups.

  14. Serum tumor necrosis factor (TNF)-alfa [ Time Frame: Day 8 ]
    Compare the levels of inflammatory mediators: tumor necrosis factor (TNF)-alfa from patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 8; verified by the measurement of cytokines in patient serum by the ELISA technique; quantified by the absolute number between the two groups.

  15. Serum interferon-gamma [ Time Frame: Day 3 ]
    Compare the levels of inflammatory mediators: interferon-gamma from patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by the measurement of cytokines in patient serum by the ELISA technique; quantified by the absolute number between the two groups.

  16. Serum interferon-gamma [ Time Frame: Day 8 ]
    Compare the levels of inflammatory mediators: interferon-gamma from patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 8; verified by the measurement of cytokines in patient serum by the ELISA technique; quantified by the absolute number between the two groups.

  17. Serum monocyte chemoattractant protein (MCP)-1 [ Time Frame: Day 3 ]
    Compare the levels of inflammatory mediators: monocyte chemoattractant protein (MCP)-1 from patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by the measurement of cytokines in patient serum by the ELISA technique; quantified by the absolute number between the two groups.

  18. Serum monocyte chemoattractant protein (MCP)-1 [ Time Frame: Day 8 ]
    Compare the levels of inflammatory mediators: monocyte chemoattractant protein (MCP)-1 from patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 8; verified by the measurement of cytokines in patient serum by the ELISA technique; quantified by the absolute number between the two groups.

  19. Complete blood count [ Time Frame: Day 3 ]
    Evaluate evolution of complete blood count 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.

  20. Complete blood count [ Time Frame: Day 8 ]
    Evaluate evolution of complete blood count with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 8; verified by laboratory tests and expressed by the absolute number between the two groups.

  21. C-reactive protein - absolute number [ Time Frame: Day 3 ]
    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.

  22. C-reactive protein - absolute number [ Time Frame: Day 8 ]
    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 8; verified by laboratory tests and expressed by the absolute number between the two groups.

  23. C-reactive protein - percentage [ Time Frame: Day 3 ]
    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 percentage between the two group.

  24. C-reactive protein - percentage [ Time Frame: Day 8 ]
    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 8; verified by laboratory tests and expressed by the percentage between the two groups.


Other Outcome Measures:
  1. Adverse events - percentage [ Time Frame: Day 8 ]
    Assess the incidence and profile of adverse events reported throughout the study, by treatment group; verified by information actively collected from patients or family members; quantified by percentage.

  2. Adverse events - absolute number [ Time Frame: Day8 ]
    Assess the incidence and profile of adverse events reported throughout the study, by treatment group; verified by information actively collected from patients or family members; quantified by absolute number.

  3. Treatment discontinuation rate - absolute number [ Time Frame: Day8 ]
    Assess the rate of treatment discontinuation due to adverse events; verified by information actively collected from patients or family members; quantified by absolute number.

  4. Treatment discontinuation rate - percentage [ Time Frame: Day8 ]
    Assess the rate of treatment discontinuation due to adverse events; verified by information actively collected from patients or family members; quantified by percentage.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Clinical scenario compatible with infection by the SARS-CoV-2 [Characteristic symptoms of COVID-19 (fever and / or cough and / or fatigue)
  • Beginning 1 to 3 days before inclusion in the study
  • Age equal or superior to 18 years
  • Willingness to receive study treatment
  • Providing written and informed consent or the same consent signed by a family member

Exclusion Criteria:

  • Negative result of RT-PCR for SARS-COV2 collected on admission
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04552483


Locations
Layout table for location information
Brazil
Universidade Federal do Rio de Janeiro
Rio De Janeiro, Brazil, 21941902
Sponsors and Collaborators
Universidade Federal do Rio de Janeiro
Ministry of Science and Technology, Brazil
National Research Council, Brazil
ATCGen
Complexo Hospitalar Municipal de São Caetano do Sul
Hospital de Transplante Doutor Euryclides de Jesus Zerbini
Secretaria Municipal de Saúde de Bauru
Santa Casa de Misericórdia de Sorocaba
Secretaria Municipal de Saúde de Guarulhos
Hospital e Maternidade Therezinha de Jesus
Secretaria de Estado de Saúde do Distrito Federal
Investigators
Layout table for investigator information
Principal Investigator: Patricia RM Rocco, MD, PhD Universidade Federal do Rio de Janeiro
Publications:
Layout table for additonal information
Responsible Party: Jose Roberto Lapa e Silva, Clinical Investigator, Universidade Federal do Rio de Janeiro
ClinicalTrials.gov Identifier: NCT04552483    
Other Study ID Numbers: SARITA-2
RBR-4nr86m ( Other Identifier: Registro Brasileiro de Ensaios Clínicos (REBEC) )
32258920.0.1001.5257 ( Other Identifier: Comitê Nacional de Ética em Pesquisa (CONEP) )
First Posted: September 17, 2020    Key Record Dates
Last Update Posted: November 3, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The investigators plan on sharing all IPD that underlie results in a publication for editorial board, with cautious of not sharing confidential data.
Supporting Materials: Study Protocol
Time Frame: Available as soon as the editorial board of the journal accepting the manuscript requires.
Access Criteria: Editorial board of the Journal accepting the manuscript.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Jose Roberto Lapa e Silva, Universidade Federal do Rio de Janeiro:
covid19
coronavirus
early treatment
COVID-19
new coronavirus
treatment
brazil
nitazoxanide
Additional relevant MeSH terms:
Layout table for MeSH terms
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Virus Diseases
Nitazoxanide
Antiparasitic Agents
Anti-Infective Agents