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

Covid19 Clinical Trial

Official title:

Effects of Nitazoxanide Administration to Patients in the Initial Phase of COVID-19

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04552483
• Other study ID #: SARITA-2
• Secondary ID: RBR-4nr86m322589
• Status: Completed
• Phase: Phase 2
• Start date: June 8, 2020
• Est. completion date: September 5, 2020

Study information

• Verified date: November 2020
• 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: 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 392
• Est. completion date: September 5, 2020
• Est. primary completion date: August 20, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Coronavirus
• Coronavirus Infections
• Covid19

Intervention

Drug:
• Nitazoxanide
Nitazoxanide 500mg 8/8 hours for 5 days in the early clinical phase of COVID-19.
• Placebo
Placebo 8/8 hours for 5 days in the early clinical phase of COVID-19.

Locations

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

Sponsors (11)

Lead Sponsor

Collaborator

Universidade Federal do Rio de Janeiro

ATCGen, Complexo Hospitalar Municipal de São Caetano do Sul, Hospital de Transplante Doutor Euryclides de Jesus Zerbini, Hospital e Maternidade Therezinha de Jesus, Ministry of Science and Technology, Brazil, National Research Council, Brazil, Santa Casa de Misericórdia de Sorocaba, Secretaria de Estado de Saúde do Distrito Federal, Secretaria Municipal de Saúde de Bauru, Secretaria Municipal de Saúde de Guarulhos

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. — 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 8
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.	Day8
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.	Day8
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.	Day8
Primary	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 information with the patient; quantified by the number of days that presented the symptom.	Day8
Primary	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 information with the patient; quantified by the number of days that presented the symptom.	Day8
Primary	Days with asthenia	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.	Day8
Secondary	SARS-COV-2 viral load - absolute number	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	Day1
Secondary	SARS-COV-2 viral load - absolute number	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.	Day8
Secondary	SARS-COV-2 viral load - percentage	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.	Day 1
Secondary	SARS-COV-2 viral load - percentage	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.	Day 8
Secondary	Hospital admission rate - absolute number	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.	Day8
Secondary	Hospital admission rate - percentage	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.	Day8
Secondary	Serum Interleukin-6	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.	Day 3
Secondary	Serum Interleukin-6	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.	Day 8
Secondary	Serum Interleukin-1-beta	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.	Day 3
Secondary	Serum Interleukin-1-beta	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.	Day 8
Secondary	Serum Interleukin-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 3; verified by the measurement of cytokines in patient serum by the ELISA technique; quantified by the absolute number between the two groups.	Day 3
Secondary	Serum Interleukin-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.	Day 8
Secondary	Serum tumor necrosis factor (TNF)-alfa	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.	Day 3
Secondary	Serum tumor necrosis factor (TNF)-alfa	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.	Day 8
Secondary	Serum interferon-gamma	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.	Day 3
Secondary	Serum interferon-gamma	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.	Day 8
Secondary	Serum monocyte chemoattractant protein (MCP)-1	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.	Day 3
Secondary	Serum monocyte chemoattractant protein (MCP)-1	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.	Day 8
Secondary	Complete blood count	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.	Day 3
Secondary	Complete blood count	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.	Day 8
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 3; verified by laboratory tests and expressed by the absolute number between the two groups.	Day 3
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 8; verified by laboratory tests and expressed by the absolute number between the two groups.	Day 8
Secondary	C-reactive protein - percentage	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.	Day 3
Secondary	C-reactive protein - percentage	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.	Day 8