Efficacy and Safety Study of Nitazoxanide (NTX) in the Treatment of Patients With SARS-CoV-2 Virus Infection (COVID-19)

October 7, 2020 updated by: Laboratorios Roemmers S.A.I.C.F.

Efficacy and Safety Study of Nitazoxanide (NTX) in the Treatment of Patients With SARS-CoC-2 Virus Infection (COVID-19). A Pilot, Randomized, Simple Blind, Placebo-controlled, Parallel-group Study

Evaluation of the efficacy and safety of NTX in adult patients (≥18 years and <60 years), with SARS-CoV-2 infection with mild symptoms of COVID-19, compared to a placebo control arm. 135 patients will be randomized to either Nitazoxanide (n=90) or placebo (n=45) (2:1). Simple blind design. Primary endpoint: eradication of virus from patients' respiratory tract secretions by the 7th day of treatment.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

The rapid spread of COVID-19 has overwhelmed the capabilities of the Public Health System in major nations due to the large number of critically ill patients and patients seriously affected requiring intensive care.

Reducing the viral load, along with other epidemiological measures, including social isolation and quarantine, may in the long run significantly reduce the R0 (Basic Reproductive Rhythm) of infection.

To date, in our country there are no specific antiviral treatments approved by the regulatory authorities for COVID-19, and no vaccines so far exist. Symptomatic and supportive treatment has been the main intervention for patients with moderate to severe infection.

The lack of a drug with a demonstrated solid antiviral efficacy warrants the need to explore new therapeutic options against SARS-CoV-2 / COVID-19.

Nitazoxanide is a widely used thiazolide, approved by the FDA and ANMAT (Argentine drug regulatory authority) as an antiprotozoal, with a very good safety record for a variety of indications. NTX was shown to have extensive antiviral activity against, inter alia, animal and human coronaviruses. Indeed, it exhibits in vitro activity against MERS-CoV and other coronaviruses, including SARS-CoV-2, where it inhibits the expression of viral protein N. Another proposed antiviral mechanism for Nitazoxanide involves PKR and eIF2α phosphorylation and the depletion of ATP-sensitive intracellular calcium deposits in infected cells, thereby inducing chronic sub-lethal stress of the endoplasmic reticulum and impairing the glycosylation of the structural protein.

Exposure in clinical trials included a specific experience on patients with uncomplicated influenza-like illness, where the drug helped reduce the mean time for symptom relief.

The objective of this study is to evaluate the efficacy and safety of NTX (1,000mg/3 times per day plus standard treatment for 14 days in male and female patients (≥ 18 years and <60 years) with COVID-19 infection, with mild symptoms, as compared to a control group treated with placebo. The proposed study dose regime of Nitazoxanide 1,000 mg/3 times per day (every 8 hours) for 14 days may be modified if patients experience considerable GI adverse effects. In these cases, the dose may be lowered to one (1) 500 mg tablet every 6 hours (2,000 mg /day). Nitazoxanide has been also administered in other studies up to 4 g daily without significant adverse effects or changes in ECG or other laboratory values.

The proposed treatment regimen is expected to reduce disease severity by earlier eradication of viral load in NTX-treated patients when compared to placebo-treated patients, thus preventing the dysregulation of the innate immune system caused by the viral infection and modifying the high mortality in older/vulnerable populations. Early virus negativization or viral load reduction can potentially reduce the severity of the symptoms, eventually preventing a liable collapse of the Health Care System and ensuring a more controlled response to the disease.

Because of its known antiviral and safety profiles, and the fact that it can be orally administered to both adults and children, as well as its rapid availability and affordability, Nitazoxanide appears as an interesting alternative for such a situation.

Statistical analysis: 1-tailed statistical test, with a 25% α value (or type I error) (p value <0.025) and a power (type II error, or β value) of 0.20 (power of 80%) for superiority of the intervention arm over the control arm. All statistical analyzes will be carried out using STATA, version 14.0.

Study Type

Interventional

Enrollment (Anticipated)

135

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Argentina
    • Buenos Aires, Argentina
      • Presidente Derqui, Buenos Aires, Argentina, Argentina, 1629

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 59 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Adult male and female patients (≥ 18 years and <60 years).
  • Signature of informed consent.
  • Patients with a positive test for SARS-CoV-2 and mild symptoms of COVID-19 (without severity criteria as detailed by the Ministry of Health of Argentina - MSN)

Exclusion Criteria:

  • Patients under 18 years of age and over 60 years of age.
  • Breastfeeding or pregnant women (with positive pregnancy blood test in women of childbearing age).
  • Patients with mild pneumonia in the presence of risk factors or moderate or severe pneumonia (based on the severity criteria set by the Ministry of Health of Argentina), or patients who require mechanical ventilation at screening.
  • Patients in whom NTX and/or lactose is contraindicated.
  • Any other contraindication based on the judgment of the treating physician.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: NTX active treatment
Intervention: NTX (500 mg every 6 hours for 14 days) orally with food (P.O.).
Drug: Nitazoxanide
NTX (500 mg every 6 hours for 14 days) orally with food (P.O.).
Placebo Comparator: Intervention: placebo
Placebo (1 tablet every 6 hours for 14 days) orally with food (P.O.).
Drug: Placebo
Placebo (1 tablet every 6 hours for 14 days) orally with food (P.O.).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Eradication of SARS COV-2 from patients' respiratory tract secretions by treatment day 7th.
Time Frame: 7 day

Erradication will be considered a reduction of the viral load on day 7 greater than 35% with respect to placebo. Extraction of genomic material will be performed using a QIAgen mini kit (QIAmp viral RNA) validated by the CDC (United States Center for Disease Control and Prevention (https://www.fda.gov/media/134922/download) (CDC-006-00019) Viral load will be quantified with the following detection kits: Commercial Kit: PCR-EUA-CDC-nCoV-IFU. Commercial KIT SENTINEL - STAT-NAT Covid 19B (Berlín).

Rational: In mild cases of COVID-19, 50% of the patients eradicated the virus within a period of 3 weeks, 25% eradicated the virus before the 13th day, 75% during the first month and the rest were " late eradicators." This latter subgroup of patients has been associated with severe cases of COVID-19 disease.
7 day

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Comparative decrease of the viral load
Time Frame: 3 - 35 days
Consequently, in mild cases, viral eradication will likely occur more frequently during the first to second week of COVID-19 disease; less than 15% could eradicate the virus during the first week of symptom onset. From an epidemiological point of view, increasing the viral eradication rate from less than 15% to more than 35% during the first two weeks of treatment would be clinically relevant.(seven), 14 (fourteen) and 35 (thirty-five) after starting treatment compared to the baseline measurement.
3 - 35 days
Clinical improvement
Time Frame: 1 - 35 days
Clinical improvement according to the WHO COVID-19 ordinal scale. Minimun 0 (zero), (best), maximum 8 (eight) (worst)
1 - 35 days
Pneumonia patients meeting severity criteria.
Time Frame: 1 - 35 days
Percentage of pneumonia patients meeting severity criteria.
1 - 35 days
Number of days with fever
Time Frame: 1 - 35 days
Number of days with fever (axillary temperature higher than 37.5°C).
1 - 35 days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Patients requiring mechanical ventilation
Time Frame: 1 - 35 days
Percentage of patients requiring mechanical ventilation through orotracheal intubation (OT) and/or ICU hospitalization.
1 - 35 days
Mortality rate.
Time Frame: 1- 35 days
Mortality rate.
1- 35 days
Lymphocyte recovery
Time Frame: 7 day
Lymphocyte recovery (absolute lymphocyte count > 1000 / mm3).
7 day
ICU hospitalization.
Time Frame: 1 - 35 days
Days of ICU hospitalization.
1 - 35 days
Oxygen saturation
Time Frame: 1 - 35 days
Oxygen saturation (SpO2) > 92% (at ambient FiO2).
1 - 35 days
Days of hospitalization
Time Frame: 1 - 35 days
Days of hospitalization
1 - 35 days
Respiratory rate
Time Frame: 1 - 35 days
Respiratory rate per minute (in afebrile state conditions).
1 - 35 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Laboratorios Roemmers S.A.I.C.F.

Investigators

  • Principal Investigator: Marcelo Silva, MD, Austral University, Argentina

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 26, 2020

Primary Completion (Anticipated)

November 15, 2020

Study Completion (Anticipated)

December 26, 2020

Study Registration Dates

First Submitted

June 26, 2020

First Submitted That Met QC Criteria

July 7, 2020

First Posted (Actual)

July 9, 2020

Study Record Updates

Last Update Posted (Actual)

October 8, 2020

Last Update Submitted That Met QC Criteria

October 7, 2020

Last Verified

June 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NTZ-COVID ARG1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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