Clinical trial NCT04561219: Nitazoxanide Therapy for Patients With COVID-19 Pneumonia
Official title: Nitazoxanide for Moderate to Severe COVID-19 Pneumonia: a Multicenter, Randomized, Placebo-controlled, Double-Blind Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Covid19
Corona Virus Infection
Pneumonia, Viral
Keywords: covid19
coronavirus
clinical trial
placebo-controlled
randomized
brazil
nitazoxanide
hospitalized patients
covid-19
sars-cov-2
new coronavirus
multicenter
double-blind
Lead sponsor: Universidade Federal do Rio de Janeiro
Sponsor class: OTHER
Collaborators: name: Ministry of Science and Technology, Brazil
name: National Research Council, Brazil
name: Financiadora de Estudos e Projetos
name: ATCGen
name: Hospital Central da Aeronáutica, Rio de Janeiro
name: Hospital da Força Aérea do Galeão
name: Hospital Naval Marcilio Dias
name: Hospital Universitario Pedro Ernesto
name: Hospital de Força Aérea de São Paulo
name: Hospital das Clínicas Luzia de Pinho Melo
name: Complexo Hospitalar Municipal de São Caetano do Sul
name: Hospital Municipal de Barueri Dr Francisco Moran
name: Hospital Regional de Sorocaba Dr Adib Domingos Jatene
name: Hospital Geral de São Mateus Dr Manoel Bifulco
name: Santa Casa de Misericórdia de Belo Horizonte
name: Mater Dei Hospital, Brazil
name: Hospital Eduardo de Menezes
name: Hospital das Clínicas da Universidade Federal de Pernambuco
name: Hospital das Forças Armadas, Brazil
name: Hospital Regional da Asa Norte, Brazil
name: Complexo Hospitalar do Trabalhador de Curitiba
name: Hospital Estadual de Doenças Tropicais Dr Anuar Auad
name: Hospital Geral de Fortaleza
First posted: 2020-09-23
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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: 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),

Eligibility criteria: 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

Primary outcomes:
measure: Orotracheal intubation rate
timeFrame: 14 days
Secondary outcomes:
measure: Hospitalisation days
timeFrame: 14 days
measure: ICU days
timeFrame: 14 days
measure: Intranasal oxygen support days
timeFrame: 14 days
measure: Mortality rate
timeFrame: 14 days
measure: Days with fever
timeFrame: 14 days
measure: Days with cough
timeFrame: 14 days
measure: Days with dyspnea
timeFrame: 14 days
measure: Radiologic findings
timeFrame: Day1
measure: Radiologic findings
timeFrame: Day7
measure: Cardiologic findings
timeFrame: Day1
measure: Cardiologic findings
timeFrame: Day7
measure: C-reactive protein - absolute number
timeFrame: Day 1
measure: C-reactive protein serum levels
timeFrame: Day 3
measure: C-reactive protein serum levels
timeFrame: Day 7
measure: Lactate dehydrogenase (LDH) serum levels
timeFrame: Day 1
measure: Lactate dehydrogenase (LDH) serum levels
timeFrame: Day 3
measure: Lactate dehydrogenase (LDH) serum levels
timeFrame: Day 7
measure: Troponin serum levels
timeFrame: Day 1
measure: Troponin serum levels
timeFrame: Day 3
measure: Troponin serum levels
timeFrame: Day 7
measure: Electrolytes serum levels
timeFrame: Day 1
measure: Electrolytes serum levels
timeFrame: Day 3
measure: Electrolytes serum levels
timeFrame: Day 7
measure: Glucose serum levels
timeFrame: Day 1
measure: Glucose serum levels
timeFrame: Day 3
measure: Glucose serum levels
timeFrame: Day 7
measure: Renal function
timeFrame: Day 1
measure: Renal function
timeFrame: Day 3
measure: Renal function
timeFrame: Day 7
measure: Coagulogram
timeFrame: Day 1
measure: Coagulogram
timeFrame: Day 3
measure: Coagulogram
timeFrame: Day 7
measure: Liver function panel
timeFrame: Day 1
measure: Liver function panel
timeFrame: Day 3
measure: Liver function panel
timeFrame: Day 7
measure: Ferritin
timeFrame: Day 1
measure: Ferritin
timeFrame: Day 3
measure: Ferritin
timeFrame: Day 7
measure: D-dimer
timeFrame: Day 1
measure: D-dimer
timeFrame: Day 3
measure: D-dimer
timeFrame: Day 7
measure: Blood cell count
timeFrame: 7 days
measure: Inflammatory mediators
timeFrame: Day 1
measure: Inflammatory mediators
timeFrame: Day 3
measure: Inflammatory mediators
timeFrame: Day 7
Other outcomes:
measure: Adverse events - percentage
timeFrame: Day 14
measure: Adverse events - absolute number
timeFrame: Day 14
measure: Treatment discontinuation rate - absolute number
timeFrame: Day 14
measure: Treatment discontinuation rate - percentage
timeFrame: Day 14
Locations:
city: Rio De Janeiro
country: Brazil
facility: Universidade Federal do Rio de Janeiro
Study officials:
affiliation: Universidade Federal do Rio de Janeiro
name: Pedro L Silva, PhD
role: STUDY_CHAIR
affiliation: Universidade Federal do Rio de Janeiro
name: Patricia RM Rocco, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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 [Preprint]. 2020 May 6:2020.05.01.20087130. doi: 10.1101/2020.05.01.20087130.
citation: 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.
citation: 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.