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Trial to Evaluate Efficacy and Safety of Nitazoxanide in the Treatment of Mild or Moderate COVID-19
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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Nitazoxanide | Active Comparator | Two nitazoxanide 300 mg tablets orally twice daily for 5 days |
|
| Placebo | Placebo Comparator | Two placebo tablets orally twice daily for 5 days |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nitazoxanide | Drug | Two nitazoxanide 300 mg tablets administered orally twice daily with food for 5 days |
|
| 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 |
| 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 |
| 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 |
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):
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.
Exclusion Criteria:
Persons with any clinical sign or symptoms suggestive of severe systemic illness with COVID-19, including the following:
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:
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.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Invesclinic US LLC | Fort Lauderdale | Florida | 33308 | United States | ||
| RH Medical Urgent Care |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35237748 | Derived | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Nitazoxanide | Two nitazoxanide 300 mg tablets orally twice daily for 5 days |
| FG001 | Placebo | Two placebo tablets orally twice daily for 5 days |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Nitazoxanide | Two nitazoxanide 300 mg tablets orally twice daily for 5 days |
| BG001 | Placebo | Two placebo tablets orally twice daily for 5 days |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | The ITTI (primary efficacy) population consisted of all subjects positive for SARS-CoV-2 by RT-PCR at Baseline. | Posted | Median | Inter-Quartile Range | days | Up to 21 days |
|
28 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Nitazoxanide | Two nitazoxanide 300 mg tablets orally twice daily for 5 days Nitazoxanide: Two nitazoxanide 300 mg tablets administered orally twice daily with food for 5 days Vitamin Super B-Complex: Vitamin Super B-Complex administered orally twice daily to maintain the blind |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ascites | Gastrointestinal disorders | MedDRA 23.0 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA 23.0 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Sr. Director, Research Operations | Romark | 8132828544 | jessica.fulgencio@romark.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 11, 2021 | Jan 24, 2024 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 24, 2021 | Jan 24, 2024 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
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| ID | Term |
|---|---|
| C041747 | nitazoxanide |
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| Placebo | Drug | Two placebo tablets administered orally twice daily with food for 5 days |
|
| Vitamin Super B-Complex | Dietary Supplement | Vitamin Super B-Complex administered orally twice daily to maintain the blind |
|
| 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 |
| The Bronx |
| New York |
| 10456 |
| United States |
| Physician Decision |
|
| Death |
|
| Protocol Violation |
|
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Height | Mean | Standard Deviation | centimeters |
|
| Weight | Mean | Standard Deviation | kilograms |
|
| BMI | Mean | Standard Deviation | kilograms per meters squared |
|
| Time from Onset of Symptoms to Randomization | Mean | Standard Deviation | hours |
|
| Tobacco Use | Count of Participants | Participants |
|
| Severity of Disease | Baseline illness severity was defined as follows: Mild illness: resting pulse <90 beats per minute and resting respiratory rate <20 breaths per minute. Moderate illness: resting pulse ≥90 beats per minute or resting respiratory rate ≥20 breaths per minute. | Count of Participants | Participants |
|
| Risk of Severe Illness | Risk was defined as follows according to data published by CDC: At Increased Risk: Subjects with COPD, Type 2 diabetes mellitus, obesity (BMI ≥30), chronic kidney disease, sickle cell disease, serious heart conditions, asthma (moderate or severe), cerebrovascular disease, cystic fibrosis, hypertension or high blood pressure, immunocompromised state, neurologic conditions, liver disease, pulmonary fibrosis, past or present history of smoking, thalassemia, or type 1 diabetes mellitus. Subjects who are ≥65 years of age. Not at Increased Risk: Subjects with none of the above conditions | Count of Participants | Participants |
|
Two placebo tablets orally twice daily for 5 days |
|
|
|
| Secondary | 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 | The ITTI (primary efficacy) population consisted of all subjects positive for SARS-CoV-2 by RT-PCR | Posted | Number | proportion of subjects | Up to 21 days |
|
|
|
|
| Other Pre-specified | Proportion of Subjects Positive for SARS-CoV-2 by Aptima® SARS-CoV-2 Assay at Each of Days 4 and 10 | The ITTI (primary efficacy) population consisted of all subjects positive for SARS-CoV-2 by RT-PCR | Posted | Number | proportion of subjects | Day 4 and Day 10 |
|
|
|
|
| Other Pre-specified | Change From Baseline in Quantitative SARS-CoV-2 RNA Measured by RT-PCR at Each of Days 4 and 10 | The ITTI (primary efficacy) population consisted of all subjects positive for SARS-CoV-2 by RT-PCR | Posted | Mean | Standard Error | log10 RNA copies/milliliter | Day 4 and Day 10 |
|
|
|
|
| Other Pre-specified | Proportion of Subjects Requiring Hospitalization | Analysis of proportions of subjects requiring hospitalization for any reason during the study period | The ITTI (primary efficacy) population consisted of all subjects positive for SARS-CoV-2 by RT-PCR | Posted | Number | proportion of subjects | 28 days |
|
|
|
|
| Other Pre-specified | All-Cause Mortality | Analysis of proportions experiencing mortality from any cause during the study period | The ITTI (primary efficacy) population consisted of all subjects positive for SARS-CoV-2 by RT-PCR | Posted | Number | proportion of subjects | 28 days |
|
|
|
|
| Post-Hoc | Time to Sustained Recovery for Subjects With Mild Illness | 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. | The ITTI (primary efficacy) population consisted of all subjects positive for SARS-CoV-2 by RT-PCR. Mild illness is defined as subjects with pulse <90 beats per minute and respiratory rate <20 breaths per minute at Baseline. | Posted | Median | Inter-Quartile Range | days | 21 days |
|
|
|
|
| Post-Hoc | Time to Return to Usual Health for Subjects With Mild Illness | Subjects completed a diary daily in the evening. The time from first dose to ability to return to usual health is the time in days from the first dose of study medication to the first time when the subject answered "Have you returned to your usual health?" with "yes" for two consecutive daily diary periods. | The ITTI (primary efficacy) population consisted of all subjects positive for SARS-CoV-2 by RT-PCR. Mild illness is defined as subjects with pulse <90 beats per minute and respiratory rate <20 breaths per minute at Baseline. | Posted | Median | Inter-Quartile Range | days | 21 days |
|
|
|
|
| Post-Hoc | Progression to Severe COVID-19 for Subjects At Least Possibly At Increased Risk Per CDC Guidelines | 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 for the subgroup of subjects considered possibly at high risk per CDC guidelines | Subjects positive for SARS-CoV-2 by RT-PCR with one of the following risk factors: COPD, Type 2 diabetes mellitus, obesity (BMI≥30), chronic kidney disease, sickle cell disease, serious heart conditions, ≥65 years of age, asthma (moderate or severe), cerebrovascular disease, cystic fibrosis, hypertension or high blood pressure, immunocompromised state, neurologic conditions, liver disease, pulmonary fibrosis, past or present history of smoking, thalassemia, Type 1 diabetes mellitus | Posted | Number | proportion of subjects | 28 days |
|
|
|
|
| Post-Hoc | Progression to Severe COVID-19 for Subjects At Increased Risk Per CDC Guidelines | 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 for the subgroup of subjects considered high risk per CDC guidelines | Subjects positive for SARS-CoV-2 by RT-PCR with one of the following risk factors: COPD, Type 2 diabetes mellitus, obesity (BMI≥30), chronic kidney disease, sickle cell disease, serious heart conditions, ≥65 years of age. | Posted | Number | proportion of subjects | 28 days |
|
|
|
|
| Post-Hoc | Progression to Severe COVID-19 in Subjects at High Risk by FDA Guidelines | 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 for the subgroup of subjects considered at high risk per FDA guidelines | Subjects positive for SARS-CoV-2 with at least one of the following risk factors: ≥ 65 years of age, BMI ≥35 kg/m2, chronic kidney disease, diabetes, immunosuppressive disease, current receipt of immunosuppressive treatment, or ≥55 years of age with at least one of cardiovascular disease, hypertension, or chronic obstructive pulmonary disease or another chronic respiratory disease. | Posted | Number | proportion of subjects | 28 days |
|
|
|
|
| 2 |
| 472 |
| 2 |
| 472 |
| 16 |
| 472 |
| EG001 | Placebo | Two placebo tablets orally twice daily for 5 days Placebo: Two placebo tablets administered orally twice daily with food for 5 days Vitamin Super B-Complex: Vitamin Super B-Complex administered orally twice daily to maintain the blind | 0 | 463 | 7 | 463 | 10 | 463 |
| COVID-19 | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
|
| COVID-19 pneumonia | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
|
| Diverticulitis | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Non-systematic Assessment |
|
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| D014777 |
| Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| 0.2814 |
| Superiority |
| 0.4974 |
| Superiority |