Nitazoxanide Therapy for Patients With COVID-19 Pneumonia

Covid19 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04561219
• Other study ID #: SARITA-1
• Secondary ID: RBR-88bs9x306624
• Status: Completed
• Phase: Phase 2
• Start date: April 19, 2020
• Est. completion date: October 2, 2020

Study information

• Verified date: July 2021
• Source: Universidade Federal do Rio de Janeiro
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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),

Recruitment information / eligibility

• Status: Completed
• Enrollment: 500
• Est. completion date: October 2, 2020
• Est. primary completion date: October 2, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Corona Virus Infection
• Coronavirus Infections
• Covid19
• Pneumonia
• Pneumonia, Viral

Intervention

Drug:
• Nitazoxanide
Nitazoxanide 500mg three times a day for 5 days
• Placebo
Placebo three times a day for 5 days

Locations

Country	Name	City	State
Brazil	Universidade Federal do Rio de Janeiro	Rio De Janeiro

Sponsors (24)

Lead Sponsor

Collaborator

Universidade Federal do Rio de Janeiro

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

Country where clinical trial is conducted

Brazil, 

References & Publications (4)

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. — View 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. 2020 May 6. pii: 2020.05.01.20087130. doi: 10.1101/2020.05.01.20087130. Update in: Br J Clin Pharmacol. 2020 Oct 21;:. — View 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. Review. — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Other	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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