COVID-19, Viral Respiratory Illnesses
Conditions
Keywords
COVID-19, Viral Respiratory Illnesses
Brief summary
Trial to Evaluate the Efficacy and Safety of Nitazoxanide (NTZ) for Pre- and Post Exposure Prophylaxis of COVID-19 and Other Viral Respiratory Illnesses (VRI) in Healthcare Workers and Others at Increased Risk of SARS-CoV-2 Infection
Detailed description
Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Nitazoxanide (NTZ) for Pre- and Post Exposure Prophylaxis of COVID-19 and Other Viral Respiratory Illnesses (VRI) in Healthcare Workers and Others at Increased Risk of SARS-CoV-2 Infection
Interventions
DRUGNitazoxanide
Nitazoxanide 600 mg administered orally twice daily for six weeks
DRUGPlacebo
Placebo administered orally twice daily for six weeks
DIETARY_SUPPLEMENTVitamin Super B-Complex
Vitamin Super B-Complex administered orally twice daily to maintain the blind
Sponsors
Romark Laboratories L.C.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
1. Males and females at least 18 years of age or of legal consenting age based on local requirements. 2. Persons at increased risk of contracting COVID-19, including: 1. Healthcare workers with known direct occupational exposure to COVID-19 within 7 days prior to enrollment. A qualifying person (i) provides healthcare to patients and/or (ii) typically positions themselves within 6 feet of patients (close contact) and (iii) is a full- time employee (average of ≥ 24 hours/week) in a high contact area (Emergency Department, Intensive Care Unit, COVID-specific Care Unit, Walk-in Clinic, Paramedic/First Responder). 2. Persons participating in social activities without the practice of generally accepted social distancing practices at least three times per week. Qualifying activities include the presence of at least 10 people in close (\<6 feet) proximity to each other without masks or other personal protective equipment (e.g., socializing at bars or community/social centers, in-home social gatherings, classes or trainings, etc.). These subjects must have engaged in such activities at least three times in the past 7 days and plan to continue these activities during the study. 3. Must have a smartphone, tablet, computer, or other qualifying internet- enabled device and daily internet access. 4. Occupational exposure to a person infected with SAR-CoV-2 within 7 days prior to enrollment or social interaction as defined in criterion 2(b). 5. Willing and able to provide written informed consent and comply with the requirements of the protocol, including completion of the subject diary.
Exclusion criteria
1. Subjects not at increased risk of contracting SARS-CoV-2 from occupational or social behaviors. 2. Subjects with known severe heart, lung, neurological or other systemic disease that the Investigator believes could preclude safe participation. 3. Subjects with a history of COVID-19 or known to have developed anti- SARS-CoV-2 antibodies or received a SARS-CoV-2 vaccine. 4. Subjects who experienced a previous episode of acute upper respiratory tract infection, otitis, bronchitis or sinusitis or received antibiotics for these conditions or antiviral therapy for influenza within two weeks prior to and including study day 1. 5. Subjects residing in the same household with another family member currently participating in the study. 6. Receipt of any dose of NTZ within 7 days prior to screening. 7. 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. 8. Known sensitivity to NTZ or any of the excipients comprising the study medication. 9. Subjects unable to swallow oral tablets or capsules. 10. 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 cycle 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. 11. Females who are breastfeeding. 12. Subjects with active respiratory allergies or subjects expected to require anti-allergy medications during the study period for respiratory allergies. 13. Subjects taking medications considered to be major CYP2C8 substrates. 14. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The Proportion of Subjects With Symptomatic Laboratory-confirmed COVID-19 Identified After Start of Treatment and Before the End of the 6-week Treatment Period. | Up to 6 weeks |
| The Proportion of Subjects With Symptomatic Laboratory-confirmed VRI Identified After the Start of Treatment and Before the End of the 6-week Treatment Period. | Up to 6 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion Experiencing Mortality Due to COVID-19 or Complications Thereof | Up to 8 weeks | Note: statistical analysis not performed because no events occurred. |
| Proportion With Anti-SARS-CoV-2 Antibodies at Either of the Week 6 or Week 8 Visits | Up to 8 weeks | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nitazoxanide Two NTZ 300 mg tablets orally twice daily for 6 weeks | 686 |
| Placebo Two placebo tablets orally twice daily for 6 weeks | 663 |
| Total | 1,349 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 2 |
| Overall Study | Lost to Follow-up | 56 | 59 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Protocol Violation | 3 | 5 |
| Overall Study | Sponsor Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 29 | 24 |
Baseline characteristics
| Characteristic | Nitazoxanide | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 40 years STANDARD_DEVIATION 13.8 | 40 years STANDARD_DEVIATION 13.8 | 40 years STANDARD_DEVIATION 13.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 219 Participants | 438 Participants | 219 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 455 Participants | 884 Participants | 429 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 12 Participants | 27 Participants | 15 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 6 Participants | 6 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 33 Participants | 58 Participants | 25 Participants |
| Race (NIH/OMB) Black or African American | 118 Participants | 241 Participants | 123 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 3 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 56 Participants | 101 Participants | 45 Participants |
| Race (NIH/OMB) White | 469 Participants | 938 Participants | 469 Participants |
| Sex: Female, Male Female | 410 Participants | 821 Participants | 411 Participants |
| Sex: Female, Male Male | 276 Participants | 528 Participants | 252 Participants |
| Weight (kg) | 84 kilograms STANDARD_DEVIATION 22.4 | 84 kilograms STANDARD_DEVIATION 22.2 | 85 kilograms STANDARD_DEVIATION 22.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 686 | 0 / 663 |
| other Total, other adverse events | 0 / 686 | 0 / 663 |
| serious Total, serious adverse events | 3 / 686 | 6 / 663 |
Outcome results
Primary
The Proportion of Subjects With Symptomatic Laboratory-confirmed COVID-19 Identified After Start of Treatment and Before the End of the 6-week Treatment Period.
Time frame: Up to 6 weeks
Population: The intent-to-treat (ITT) population consists of all subjects who received at least one dose of study medication and were negative for all respiratory viruses tested at Baseline. Proportions were rounded to the nearest hundredth decimal.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nitazoxanide | The Proportion of Subjects With Symptomatic Laboratory-confirmed COVID-19 Identified After Start of Treatment and Before the End of the 6-week Treatment Period. | 0.02 proportion of participants |
| Placebo | The Proportion of Subjects With Symptomatic Laboratory-confirmed COVID-19 Identified After Start of Treatment and Before the End of the 6-week Treatment Period. | 0.02 proportion of participants |
p-value: 0.943495% CI: [0.4696, 2.2546]Cochran-Mantel-Haenszel
Primary
The Proportion of Subjects With Symptomatic Laboratory-confirmed VRI Identified After the Start of Treatment and Before the End of the 6-week Treatment Period.
Time frame: Up to 6 weeks
Population: The intent-to-treat (ITT) population consists of all subjects who received at least one dose of study medication and were negative for all respiratory viruses tested at Baseline. Proportions were rounded to the nearest hundredth decimal.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nitazoxanide | The Proportion of Subjects With Symptomatic Laboratory-confirmed VRI Identified After the Start of Treatment and Before the End of the 6-week Treatment Period. | 0.05 proportion of participants |
| Placebo | The Proportion of Subjects With Symptomatic Laboratory-confirmed VRI Identified After the Start of Treatment and Before the End of the 6-week Treatment Period. | 0.05 proportion of participants |
p-value: 0.680595% CI: [0.6623, 1.8813]Cochran-Mantel-Haenszel
Secondary
Proportion Experiencing Mortality Due to COVID-19 or Complications Thereof
Note: statistical analysis not performed because no events occurred.
Time frame: Up to 8 weeks
Population: The intent-to-treat (ITT) population consists of all subjects who received at least one dose of study medication and were negative for all respiratory viruses tested at Baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nitazoxanide | Proportion Experiencing Mortality Due to COVID-19 or Complications Thereof | 0 proportion of participants |
| Placebo | Proportion Experiencing Mortality Due to COVID-19 or Complications Thereof | 0 proportion of participants |
Secondary
Proportion With Anti-SARS-CoV-2 Antibodies at Either of the Week 6 or Week 8 Visits
Time frame: Up to 8 weeks
Population: The intent-to-treat (ITT) population consists of all subjects who received at least one dose of study medication and were negative for all respiratory viruses tested at Baseline. Proportions were rounded to the nearest hundredth decimal.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nitazoxanide | Proportion With Anti-SARS-CoV-2 Antibodies at Either of the Week 6 or Week 8 Visits | 0.17 proportion of participants |
| Placebo | Proportion With Anti-SARS-CoV-2 Antibodies at Either of the Week 6 or Week 8 Visits | 0.19 proportion of participants |
p-value: 0.3459Cochran-Mantel-Haenszel
Post Hoc
Days Meeting Acute Respiratory Illness Symptom Severity Criteria Due to COVID-19
Descriptive statistics of the number of days patients with symptomatic COVID-19 met the protocol-specified acute respiratory illness symptom severity criteria due to COVID-19
Time frame: Up to 56 days
Population: Patients with symptomatic COVID-19
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nitazoxanide | Days Meeting Acute Respiratory Illness Symptom Severity Criteria Due to COVID-19 | 10.0 days | Standard Deviation 15.52 |
| Placebo | Days Meeting Acute Respiratory Illness Symptom Severity Criteria Due to COVID-19 | 13.8 days | Standard Deviation 12.05 |
Post Hoc
Days Meeting Acute Respiratory Illness Symptom Severity Criteria Due to VRI
Descriptive statistics of the number of days patients with symptomatic viral respiratory illness (VRI) met the protocol-specified acute respiratory illness symptom severity criteria due to VRI
Time frame: Up to 56 days
Population: Participants with symptomatic viral respiratory illness (VRI)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nitazoxanide | Days Meeting Acute Respiratory Illness Symptom Severity Criteria Due to VRI | 7.3 days | Standard Deviation 10.97 |
| Placebo | Days Meeting Acute Respiratory Illness Symptom Severity Criteria Due to VRI | 11.4 days | Standard Deviation 12.73 |
Post Hoc
Days Not at Usual Health Due to COVID-19
Descriptive statistics of the number of days patients with symptomatic COVID-19 report not being at usual health due to COVID-19
Time frame: Up to 56 days
Population: Participants experiencing symptomatic COVID-19 during the study period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nitazoxanide | Days Not at Usual Health Due to COVID-19 | 13.2 days | Standard Deviation 16.88 |
| Placebo | Days Not at Usual Health Due to COVID-19 | 19.5 days | Standard Deviation 14.58 |
Post Hoc
Days Not At Usual Health Due to VRI
Descriptive statistics of the number of days patients with symptomatic viral respiratory illness (VRI) report not being at usual health due to VRI
Time frame: Up to 56 days
Population: Participants experiencing symptomatic viral respiratory illness
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nitazoxanide | Days Not At Usual Health Due to VRI | 9.9 days | Standard Deviation 12.19 |
| Placebo | Days Not At Usual Health Due to VRI | 14.4 days | Standard Deviation 14.44 |
Post Hoc
Days Unable to Perform Usual Activities Due to COVID-19
Descriptive statistics of the number of days patients with symptomatic COVID-19 report being unable to perform usual activities due to COVID-19
Time frame: Up to 56 days
Population: Patients with symptomatic COVID-19
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nitazoxanide | Days Unable to Perform Usual Activities Due to COVID-19 | 8.2 days | Standard Deviation 11.73 |
| Placebo | Days Unable to Perform Usual Activities Due to COVID-19 | 16.5 days | Standard Deviation 12.72 |
Post Hoc
Days Unable to Perform Usual Activities Due to VRI
Descriptive statistics of the number of days patients with symptomatic viral respiratory illness (VRI) report being unable to perform usual activities due to VRI
Time frame: Up to 56 days
Population: Participants experiencing symptomatic viral respiratory illness (VRI)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nitazoxanide | Days Unable to Perform Usual Activities Due to VRI | 5.9 days | Standard Deviation 8.85 |
| Placebo | Days Unable to Perform Usual Activities Due to VRI | 9.7 days | Standard Deviation 11.61 |
Post Hoc
Maximum Symptom Severity Due to COVID-19
Descriptive statistics of the maximum symptom severity reported by patients with symptomatic COVID-19. The global assessment of symptom severity was reported by patients as absent, mild, moderate, severe, or very severe and coded as 0, 1, 2, 3, or 4, respectively.
Time frame: Up to 56 days
Population: Participants with symptomatic COVID-19
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nitazoxanide | Maximum Symptom Severity Due to COVID-19 | 1.3 score on a scale | Standard Deviation 0.95 |
| Placebo | Maximum Symptom Severity Due to COVID-19 | 2.3 score on a scale | Standard Deviation 1.11 |
Post Hoc
Maximum Symptom Severity Due to VRI
Descriptive statistics of the maximum symptom severity reported by patients with symptomatic viral respiratory illness (VRI). The global assessment of symptom severity was reported by patients as absent, mild, moderate, severe, or very severe and coded as 0, 1, 2, 3, or 4, respectively.
Time frame: Up to 56 days
Population: Participants with symptomatic viral respiratory illness (VRI)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nitazoxanide | Maximum Symptom Severity Due to VRI | 1.6 score on a scale | Standard Deviation 0.98 |
| Placebo | Maximum Symptom Severity Due to VRI | 1.9 score on a scale | Standard Deviation 1.01 |