Trial to Evaluate Efficacy and Safety of Nitazoxanide in the Treatment of Mild or Moderate COVID-19

Phase 3, Randomized, Double-Blind, Placebo-Controlled, Trial to Evaluate Efficacy and Safety of Nitazoxanide in the Treatment of Mild or Moderate COVID-19

Trial to Evaluate Efficacy and Safety of Nitazoxanide in the Treatment of Mild or Moderate COVID-19

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Drug: Nitazoxanide; Dietary supplement: Vitamin Super B-Complex; Drug: Placebo

Detailed Description

Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate Efficacy and Safety of Nitazoxanide in the Treatment of Mild or Moderate COVID-19

• Study Type: Interventional
• Enrollment (Actual): 935
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Invesclinic US LLC
  • New York
    • Bronx, New York, United States, 10456
      • RH Medical Urgent Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 120 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female outpatients at least 12 years of age

• Presence of clinical signs and/or symptoms consistent with worsening or stable mild or moderate COVID-19 (one of the following is required):

  1. Presence of at least two respiratory symptom domains (head, throat, nose, chest, cough) with a score of ≥2 as determined by Screening FLU-PRO OR
  2. Presence of at least one respiratory symptom domain (head, throat, nose, chest, cough) with a score of ≥2 as determined by Screening FLU-PRO with pulse rate ≥90 OR
  3. Presence of at least one respiratory symptom domain (head, throat, nose, chest, cough) with a score of ≥2 as determined by Screening FLU-PRO with respiratory rate ≥16

AND patient reported assessment that symptoms are present, the symptoms are not consistent with the subject's usual health, the symptoms interfere with daily activities, and the symptoms have worsened or remained the same relative to the previous day, as confirmed by responses to questions in the Screening FLU-PRO.

• Onset of symptoms no more than 72 hours before enrollment in the trial. Onset of symptoms is defined as the earlier of the first time at which the subject experienced subjective fever or any respiratory symptom (head, throat, nose, chest, or cough symptoms).
• Willing and able to provide written informed consent (including assent by legal guardian if under 18 years of age) and comply with the requirements of the protocol, including completion of the subject diary and all protocol procedures.

Exclusion Criteria:

• Persons with any clinical sign or symptoms suggestive of severe systemic illness with COVID-19, including the following:

  1. shortness of breath at rest,
  2. resting pulse ≥125 beats per minute,
  3. resting respiratory rate ≥30 breaths per minute, or
  4. SpO2 ≤ 93% on room air at sea level.
• Subjects who experienced a previous episode of acute upper respiratory tract infection, otitis, bronchitis or sinusitis or received antibiotics for these conditions within two weeks prior to and including study day 1.

• Severely immunodeficient persons including:

  1. Subjects with immunologic disorders or receiving immunosuppressive therapy (e.g., for organ or bone marrow transplants, immunomodulatory therapies for certain autoimmune diseases)
  2. Subjects with untreated human immunodeficiency virus (HIV) infection or treated human immunodeficiency virus (HIV) infection with a CD4 count below 350 cells/mm3 in the last six months
  3. Subjects actively undergoing systemic chemotherapy or radiotherapy treatment for malignancy
  4. Subjects using steroids as maintenance therapy for chronic conditions
• Subjects with active respiratory allergies or subjects expected to require anti- allergy medications during the study period for respiratory allergies.
• Females of childbearing potential who are either pregnant or sexually active without the use of birth control. Female subjects of child-bearing potential that are sexually active must have a negative baseline pregnancy test and must agree to continue an acceptable method of birth control for the duration of the study and for 1 month post-treatment. A double barrier method, oral birth control pills administered for at least 2 monthly cycles prior to study drug administration, an intrauterine device (IUD), or medroxyprogesterone acetate administered intramuscularly for a minimum of one month prior to study drug administration are acceptable methods of birth control for inclusion into the study. Female subjects are considered of childbearing potential unless they are postmenopausal (absence of menstrual bleeding for 1 year - or 6 months if laboratory confirmation of hormonal status), or have had a hysterectomy, bilateral tubular ligation or bilateral oophorectomy.
• Subjects with a history of COVID-19 or known to have developed anti-SARS- CoV-2 antibodies.
• Subjects residing in the same household with another subject participating in the study.
• Treatment with any investigational drug or vaccine therapy within 30 days prior to screening and willing to avoid them during the course of the study.
• Receipt of any dose of nitazoxanide within seven days prior to screening.
• Known sensitivity to nitazoxanide or any of the excipients comprising the study medication.
• Subjects unable to swallow oral tablets or capsules.
• Subjects with known severe heart, lung, neurological or other systemic disease that the Investigator believes could preclude safe participation.
• Subjects likely or expected to require hospitalization unrelated to COVID-19 during the study period.
• Subjects taking medications considered to be major CYP2C8 substrates.
• Subjects who, in the judgment of the Investigator, will be unlikely to comply with the requirements of this protocol including completion of the subject diary.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Nitazoxanide; Two nitazoxanide 300 mg tablets orally twice daily for 5 days	Drug: Nitazoxanide; Two nitazoxanide 300 mg tablets administered orally twice daily with food for 5 days; Other Names: NTZ (nitazoxanide); NT-300; Dietary supplement: Vitamin Super B-Complex; Vitamin Super B-Complex administered orally twice daily to maintain the blind
Placebo Comparator: Placebo; Two placebo tablets orally twice daily for 5 days	Dietary supplement: Vitamin Super B-Complex; Vitamin Super B-Complex administered orally twice daily to maintain the blind; Drug: Placebo; Two placebo tablets administered orally twice daily with food for 5 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Sustained Clinical Recovery	Time to Sustained Clinical Recovery is the time in days from the first dose of study medication to the first time at which the subject reports a decrease in total FLU-PRO score from the previous diary with assessment that symptoms are at least "somewhat better than yesterday", no oral temperature ≥100.4 F in the prior 24 hours, and no future increase in any of the FLU-PRO domains except within validated background levels.	Up to 21 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Subjects Progressing to Severe COVID-19	Analysis of proportions of subjects with progression to severe COVID-19 illness defined as subject-reported shortness of breath at rest and blood oxygen saturation ≤93% on room air	Up to 21 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Subjects Positive for SARS-CoV-2 by Aptima® SARS-CoV-2 Assay at Each of Days 4 and 10		Day 4 and Day 10
Change From Baseline in Quantitative SARS-CoV-2 RNA Measured by RT-PCR at Each of Days 4 and 10		Day 4 and Day 10
Proportion of Subjects Requiring Hospitalization	Analysis of proportions of subjects requiring hospitalization for any reason during the study period	28 days
All-Cause Mortality	Analysis of proportions experiencing mortality from any cause during the study period	28 days

Collaborators and Investigators

• Sponsor: Romark Laboratories L.C.

Publications and helpful links

General Publications

• Rossignol JF, Bardin MC, Fulgencio J, Mogelnicki D, Brechot C. A randomized double-blind placebo-controlled clinical trial of nitazoxanide for treatment of mild or moderate COVID-19. EClinicalMedicine. 2022 Feb 28;45:101310. doi: 10.1016/j.eclinm.2022.101310. eCollection 2022 Mar.

Study record dates

Study Major Dates

• Study Start (Actual): August 13, 2020
• Primary Completion (Actual): February 8, 2021
• Study Completion (Actual): February 8, 2021

Study Registration Dates

• First Submitted: July 23, 2020
• First Submitted That Met QC Criteria: July 23, 2020
• First Posted (Actual): July 24, 2020

Study Record Updates

• Last Update Posted (Actual): March 29, 2024
• Last Update Submitted That Met QC Criteria: March 28, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Anti-Infective Agents; Antiparasitic Agents; Nitazoxanide
• Other Study ID Numbers: RM08-3008

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No