Nitazoxanide Therapy for Patients With COVID-19 Pneumonia

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

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.

Study Overview

• Status: Completed
• Conditions: Pneumonia, Viral; Covid19; Corona Virus Infection
• Intervention / Treatment: Drug: Nitazoxanide; Drug: Placebo

Detailed Description

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),

• Study Type: Interventional
• Enrollment (Actual): 500
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Rio De Janeiro, Brazil, 21941902
    • Universidade Federal do Rio de Janeiro

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nitazoxanide; Patients received nitazoxanide 500mg 8/8hours, for 5 days.	Drug: Nitazoxanide; Nitazoxanide 500mg three times a day for 5 days; Other Names: azox; annita; irose; tanisea; trinida; zoxany
Placebo Comparator: Placebo; Patients received placebo 500mg 8/8hours, for 5 days	Drug: Placebo; Placebo three times a day for 5 days

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events - percentage	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.	Day 14
Adverse events - absolute number	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.	Day 14
Treatment discontinuation rate - absolute number	Assess the rate of treatment discontinuation due to adverse events; verified by information actively collected from patients or family members; quantified by absolute number.	Day 14
Treatment discontinuation rate - percentage	Assess the rate of treatment discontinuation due to adverse events; verified by information actively collected from patients or family members; quantified by percentage.	Day 14

Collaborators and Investigators

• Sponsor: Universidade Federal do Rio de Janeiro
• Collaborators: Financiadora de Estudos e Projetos; Hospital Universitario Pedro Ernesto; National Research Council, Brazil; Santa Casa de Misericórdia de Belo Horizonte; Ministry of Science and Technology, Brazil; ATCGen; Complexo Hospitalar Municipal de São Caetano do Sul; Hospital das Forças Armadas, Brazil; Hospital Geral de Fortaleza; Hospital Central da Aeronáutica, Rio de Janeiro; Hospital da Força Aérea do Galeão; Hospital Naval Marcilio Dias; Hospital de Força Aérea de São Paulo; Hospital das Clínicas Luzia de Pinho Melo; Hospital Municipal de Barueri Dr Francisco Moran; Hospital Regional de Sorocaba Dr Adib Domingos Jatene; Hospital Geral de São Mateus Dr Manoel Bifulco; Mater Dei Hospital, Brazil; Hospital Eduardo de Menezes; Hospital das Clínicas da Universidade Federal de Pernambuco; Hospital Regional da Asa Norte, Brazil; Complexo Hospitalar do Trabalhador de Curitiba; Hospital Estadual de Doenças Tropicais Dr Anuar Auad
• Investigators: Principal Investigator: Patricia RM Rocco, MD, PhD, Universidade Federal do Rio de Janeiro; Study Chair: Pedro L Silva, PhD, Universidade Federal do Rio de Janeiro

Publications and helpful links

General Publications

• Rossignol JF. Nitazoxanide: a first-in-class broad-spectrum antiviral agent. Antiviral Res. 2014 Oct;110:94-103. doi: 10.1016/j.antiviral.2014.07.014. Epub 2014 Aug 7.
• Rossignol JF. Nitazoxanide, a new drug candidate for the treatment of Middle East respiratory syndrome coronavirus. J Infect Public Health. 2016 May-Jun;9(3):227-30. doi: 10.1016/j.jiph.2016.04.001. Epub 2016 Apr 16.
• Rajoli RK, Pertinez H, Arshad U, Box H, Tatham L, Curley P, Neary M, Sharp J, Liptrott NJ, Valentijn A, David C, Rannard SP, Aljayyoussi G, Pennington SH, Hill A, Boffito M, Ward SA, Khoo SH, Bray PG, O'Neill PM, Hong WD, Biagini G, Owen A. Dose prediction for repurposing nitazoxanide in SARS-CoV-2 treatment or chemoprophylaxis. medRxiv. 2020 May 6:2020.05.01.20087130. doi: 10.1101/2020.05.01.20087130. Preprint.
• Pepperrell T, Pilkington V, Owen A, Wang J, Hill AM. Review of safety and minimum pricing of nitazoxanide for potential treatment of COVID-19. J Virus Erad. 2020 Apr 30;6(2):52-60. doi: 10.1016/S2055-6640(20)30017-0.
• Rocco PRM, Silva PL, Cruz FF, Tierno PFGMM, Rabello E, Junior JC, Haag F, de Avila RE, da Silva JDG, Mamede MMS, Buchele KS, Barbosa LCV, Cabral AC, Junqueira AAF, Araujo-Filho JA, da Costa LATJ, Alvarenga PPM, Moura AS, Carajeleascow R, de Oliveira MC, Silva RGF, Soares CRP, Fernandes APSM, Fonseca FG, Camargos VN, Reis JS, Franchini KG, Luiz RR, Morais S, Sverdloff C, Martins CM, Felix NS, Mattos-Silva P, Nogueira CMB, Caldeira DAF, Pelosi P, Lapa-E-Silva JR. Nitazoxanide in Patients Hospitalized With COVID-19 Pneumonia: A Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial. Front Med (Lausanne). 2022 Apr 13;9:844728. doi: 10.3389/fmed.2022.844728. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2020
• Primary Completion (Actual): October 2, 2020
• Study Completion (Actual): October 2, 2020

Study Registration Dates

• First Submitted: September 22, 2020
• First Submitted That Met QC Criteria: September 22, 2020
• First Posted (Actual): September 23, 2020

Study Record Updates

• Last Update Posted (Actual): July 22, 2021
• Last Update Submitted That Met QC Criteria: July 15, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: clinical trial; covid19; sars-cov-2; coronavirus; covid-19; multicenter; randomized; placebo-controlled; double-blind; nitazoxanide; hospitalized patients; new coronavirus; brazil
• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; COVID-19; Coronavirus Infections; Pneumonia; Pneumonia, Viral; Anti-Infective Agents; Antiparasitic Agents; Nitazoxanide
• Other Study ID Numbers: SARITA-1; RBR-88bs9x (Other Identifier: Registro Brasileiro de Ensaios Clínicos (REBEC)); 30662420.0.1001.0008 (Other Identifier: Comitê Nacional de Ética em Pesquisa (CONEP))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD 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.
• IPD Sharing Time Frame: Available as soon as the editorial board of the journal accepting the manuscript requires.
• IPD Sharing Access Criteria: Editorial board of the Journal accepting the manuscript.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)

Drug and device information, study documents

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