Clinical trial NCT04552483: Effects of Early Use of Nitazoxanide in Patients With COVID-19
Official title: Effects of Nitazoxanide Administration to Patients in the Initial Phase of COVID-19
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Covid19
Coronavirus
Keywords: covid19
coronavirus
early treatment
COVID-19
new coronavirus
treatment
brazil
nitazoxanide
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: ATCGen
name: Complexo Hospitalar Municipal de São Caetano do Sul
name: Hospital de Transplante Doutor Euryclides de Jesus Zerbini
name: Secretaria Municipal de Saúde de Bauru
name: Santa Casa de Misericórdia de Sorocaba
name: Secretaria Municipal de Saúde de Guarulhos
name: Hospital e Maternidade Therezinha de Jesus
name: Secretaria de Estado de Saúde do Distrito Federal
First posted: 2020-09-17
Enrollment: 392
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

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).

Eligibility 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

Primary outcomes:
measure: Days with fever
timeFrame: Day8
measure: Days with cough
timeFrame: Day8
measure: Days with asthenia
timeFrame: Day8
Secondary outcomes:
measure: SARS-COV-2 viral load - absolute number
timeFrame: Day1
measure: SARS-COV-2 viral load - absolute number
timeFrame: Day8
measure: SARS-COV-2 viral load - percentage
timeFrame: Day 1
measure: SARS-COV-2 viral load - percentage
timeFrame: Day 8
measure: Hospital admission rate - absolute number
timeFrame: Day8
measure: Hospital admission rate - percentage
timeFrame: Day8
measure: Serum Interleukin-6
timeFrame: Day 3
measure: Serum Interleukin-6
timeFrame: Day 8
measure: Serum Interleukin-1-beta
timeFrame: Day 3
measure: Serum Interleukin-1-beta
timeFrame: Day 8
measure: Serum Interleukin-8
timeFrame: Day 3
measure: Serum Interleukin-8
timeFrame: Day 8
measure: Serum tumor necrosis factor (TNF)-alfa
timeFrame: Day 3
measure: Serum tumor necrosis factor (TNF)-alfa
timeFrame: Day 8
measure: Serum interferon-gamma
timeFrame: Day 3
measure: Serum interferon-gamma
timeFrame: Day 8
measure: Serum monocyte chemoattractant protein (MCP)-1
timeFrame: Day 3
measure: Serum monocyte chemoattractant protein (MCP)-1
timeFrame: Day 8
measure: Complete blood count
timeFrame: Day 3
measure: Complete blood count
timeFrame: Day 8
measure: C-reactive protein - absolute number
timeFrame: Day 3
measure: C-reactive protein - absolute number
timeFrame: Day 8
measure: C-reactive protein - percentage
timeFrame: Day 3
measure: C-reactive protein - percentage
timeFrame: Day 8
Other outcomes:
measure: Adverse events - percentage
timeFrame: Day 8
measure: Adverse events - absolute number
timeFrame: Day8
measure: Treatment discontinuation rate - absolute number
timeFrame: Day8
measure: Treatment discontinuation rate - percentage
timeFrame: Day8
Locations:
city: Rio De Janeiro
country: Brazil
facility: Universidade Federal do Rio de Janeiro
Study officials:
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.