Trial Outcomes & Findings for Trial to Evaluate Efficacy and Safety of Nitazoxanide in the Treatment of Mild or Moderate COVID-19 (NCT NCT04486313)
NCT ID: NCT04486313
Last Updated: 2024-03-29
Results Overview
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.
COMPLETED
PHASE3
935 participants
Up to 21 days
2024-03-29
Participant Flow
Participant milestones
| Measure |
Nitazoxanide
Two nitazoxanide 300 mg tablets orally twice daily for 5 days
|
Placebo
Two placebo tablets orally twice daily for 5 days
|
|---|---|---|
|
Overall Study
STARTED
|
472
|
463
|
|
Overall Study
COMPLETED
|
453
|
446
|
|
Overall Study
NOT COMPLETED
|
19
|
17
|
Reasons for withdrawal
| Measure |
Nitazoxanide
Two nitazoxanide 300 mg tablets orally twice daily for 5 days
|
Placebo
Two placebo tablets orally twice daily for 5 days
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
7
|
9
|
|
Overall Study
Withdrawal by Subject
|
8
|
6
|
|
Overall Study
Physician Decision
|
1
|
1
|
|
Overall Study
Death
|
2
|
0
|
|
Overall Study
Protocol Violation
|
1
|
1
|
Baseline Characteristics
Trial to Evaluate Efficacy and Safety of Nitazoxanide in the Treatment of Mild or Moderate COVID-19
Baseline characteristics by cohort
| Measure |
Nitazoxanide
n=472 Participants
Two nitazoxanide 300 mg tablets orally twice daily for 5 days
|
Placebo
n=463 Participants
Two placebo tablets orally twice daily for 5 days
|
Total
n=935 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
40.2 years
STANDARD_DEVIATION 14.83 • n=99 Participants
|
40.7 years
STANDARD_DEVIATION 14.68 • n=107 Participants
|
40.5 years
STANDARD_DEVIATION 14.75 • n=206 Participants
|
|
Sex: Female, Male
Female
|
282 Participants
n=99 Participants
|
284 Participants
n=107 Participants
|
566 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
190 Participants
n=99 Participants
|
179 Participants
n=107 Participants
|
369 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
117 Participants
n=99 Participants
|
112 Participants
n=107 Participants
|
229 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
349 Participants
n=99 Participants
|
343 Participants
n=107 Participants
|
692 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
6 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
14 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
5 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
12 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
6 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
11 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
41 Participants
n=99 Participants
|
43 Participants
n=107 Participants
|
84 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
404 Participants
n=99 Participants
|
388 Participants
n=107 Participants
|
792 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
14 Participants
n=99 Participants
|
19 Participants
n=107 Participants
|
33 Participants
n=206 Participants
|
|
Height
|
169.1 centimeters
STANDARD_DEVIATION 10.84 • n=99 Participants
|
168.4 centimeters
STANDARD_DEVIATION 9.96 • n=107 Participants
|
168.7 centimeters
STANDARD_DEVIATION 10.41 • n=206 Participants
|
|
Weight
|
88.0 kilograms
STANDARD_DEVIATION 24.44 • n=99 Participants
|
88.5 kilograms
STANDARD_DEVIATION 23.36 • n=107 Participants
|
88.3 kilograms
STANDARD_DEVIATION 23.90 • n=206 Participants
|
|
BMI
|
30.7 kilograms per meters squared
STANDARD_DEVIATION 7.72 • n=99 Participants
|
31.1 kilograms per meters squared
STANDARD_DEVIATION 7.51 • n=107 Participants
|
30.9 kilograms per meters squared
STANDARD_DEVIATION 7.62 • n=206 Participants
|
|
Time from Onset of Symptoms to Randomization
|
41.5 hours
STANDARD_DEVIATION 15.73 • n=99 Participants
|
41.9 hours
STANDARD_DEVIATION 16.71 • n=107 Participants
|
41.7 hours
STANDARD_DEVIATION 16.21 • n=206 Participants
|
|
Tobacco Use
Current Tobacco User
|
115 Participants
n=99 Participants
|
106 Participants
n=107 Participants
|
221 Participants
n=206 Participants
|
|
Tobacco Use
Past Tobacco User
|
62 Participants
n=99 Participants
|
69 Participants
n=107 Participants
|
131 Participants
n=206 Participants
|
|
Tobacco Use
Never Used Tobacco
|
295 Participants
n=99 Participants
|
288 Participants
n=107 Participants
|
583 Participants
n=206 Participants
|
|
Severity of Disease
Mild Illness
|
301 Participants
n=99 Participants
|
305 Participants
n=107 Participants
|
606 Participants
n=206 Participants
|
|
Severity of Disease
Moderate Illness
|
170 Participants
n=99 Participants
|
158 Participants
n=107 Participants
|
328 Participants
n=206 Participants
|
|
Severity of Disease
Unknown
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Risk of Severe Illness
At Increased Risk of Severe Illness
|
330 Participants
n=99 Participants
|
338 Participants
n=107 Participants
|
668 Participants
n=206 Participants
|
|
Risk of Severe Illness
Not At Increased Risk of Severe Illness
|
142 Participants
n=99 Participants
|
125 Participants
n=107 Participants
|
267 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Up to 21 daysPopulation: The ITTI (primary efficacy) population consisted of all subjects positive for SARS-CoV-2 by RT-PCR at Baseline.
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.
Outcome measures
| Measure |
Nitazoxanide
n=184 Participants
Two nitazoxanide 300 mg tablets orally twice daily for 5 days
|
Placebo
n=194 Participants
Two placebo tablets orally twice daily for 5 days
|
|---|---|---|
|
Time to Sustained Clinical Recovery
|
13.3 days
Interval 6.26 to 21.0
|
12.4 days
Interval 7.18 to 21.0
|
SECONDARY outcome
Timeframe: Up to 21 daysPopulation: The ITTI (primary efficacy) population consisted of all subjects positive for SARS-CoV-2 by RT-PCR
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
Outcome measures
| Measure |
Nitazoxanide
n=184 Participants
Two nitazoxanide 300 mg tablets orally twice daily for 5 days
|
Placebo
n=195 Participants
Two placebo tablets orally twice daily for 5 days
|
|---|---|---|
|
Proportion of Subjects Progressing to Severe COVID-19
|
0.005 proportion of subjects
|
0.036 proportion of subjects
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 4 and Day 10Population: The ITTI (primary efficacy) population consisted of all subjects positive for SARS-CoV-2 by RT-PCR
Outcome measures
| Measure |
Nitazoxanide
n=184 Participants
Two nitazoxanide 300 mg tablets orally twice daily for 5 days
|
Placebo
n=195 Participants
Two placebo tablets orally twice daily for 5 days
|
|---|---|---|
|
Proportion of Subjects Positive for SARS-CoV-2 by Aptima® SARS-CoV-2 Assay at Each of Days 4 and 10
Day 4
|
0.908 proportion of subjects
|
0.862 proportion of subjects
|
|
Proportion of Subjects Positive for SARS-CoV-2 by Aptima® SARS-CoV-2 Assay at Each of Days 4 and 10
Day 10
|
0.707 proportion of subjects
|
0.662 proportion of subjects
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 4 and Day 10Population: The ITTI (primary efficacy) population consisted of all subjects positive for SARS-CoV-2 by RT-PCR
Outcome measures
| Measure |
Nitazoxanide
n=184 Participants
Two nitazoxanide 300 mg tablets orally twice daily for 5 days
|
Placebo
n=195 Participants
Two placebo tablets orally twice daily for 5 days
|
|---|---|---|
|
Change From Baseline in Quantitative SARS-CoV-2 RNA Measured by RT-PCR at Each of Days 4 and 10
Day 10
|
-2.49 log10 RNA copies/milliliter
Standard Error 0.119
|
-2.61 log10 RNA copies/milliliter
Standard Error 0.120
|
|
Change From Baseline in Quantitative SARS-CoV-2 RNA Measured by RT-PCR at Each of Days 4 and 10
Day 4
|
-0.70 log10 RNA copies/milliliter
Standard Error 0.118
|
-1.02 log10 RNA copies/milliliter
Standard Error 0.126
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 28 daysPopulation: The ITTI (primary efficacy) population consisted of all subjects positive for SARS-CoV-2 by RT-PCR
Analysis of proportions of subjects requiring hospitalization for any reason during the study period
Outcome measures
| Measure |
Nitazoxanide
n=184 Participants
Two nitazoxanide 300 mg tablets orally twice daily for 5 days
|
Placebo
n=195 Participants
Two placebo tablets orally twice daily for 5 days
|
|---|---|---|
|
Proportion of Subjects Requiring Hospitalization
|
0.005 proportion of subjects
|
0.026 proportion of subjects
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 28 daysPopulation: The ITTI (primary efficacy) population consisted of all subjects positive for SARS-CoV-2 by RT-PCR
Analysis of proportions experiencing mortality from any cause during the study period
Outcome measures
| Measure |
Nitazoxanide
n=184 Participants
Two nitazoxanide 300 mg tablets orally twice daily for 5 days
|
Placebo
n=195 Participants
Two placebo tablets orally twice daily for 5 days
|
|---|---|---|
|
All-Cause Mortality
|
0.005 proportion of subjects
|
0.000 proportion of subjects
|
POST_HOC outcome
Timeframe: 21 daysPopulation: 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.
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.
Outcome measures
| Measure |
Nitazoxanide
n=116 Participants
Two nitazoxanide 300 mg tablets orally twice daily for 5 days
|
Placebo
n=130 Participants
Two placebo tablets orally twice daily for 5 days
|
|---|---|---|
|
Time to Sustained Recovery for Subjects With Mild Illness
|
10.3 days
Interval 6.2 to 21.0
|
13.4 days
Interval 7.4 to 21.0
|
POST_HOC outcome
Timeframe: 21 daysPopulation: 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.
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.
Outcome measures
| Measure |
Nitazoxanide
n=116 Participants
Two nitazoxanide 300 mg tablets orally twice daily for 5 days
|
Placebo
n=130 Participants
Two placebo tablets orally twice daily for 5 days
|
|---|---|---|
|
Time to Return to Usual Health for Subjects With Mild Illness
|
13.2 days
Interval 9.2 to 21.0
|
18.4 days
Interval 11.4 to 21.0
|
POST_HOC outcome
Timeframe: 28 daysPopulation: 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
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
Outcome measures
| Measure |
Nitazoxanide
n=112 Participants
Two nitazoxanide 300 mg tablets orally twice daily for 5 days
|
Placebo
n=126 Participants
Two placebo tablets orally twice daily for 5 days
|
|---|---|---|
|
Progression to Severe COVID-19 for Subjects At Least Possibly At Increased Risk Per CDC Guidelines
|
0.009 proportion of subjects
|
0.056 proportion of subjects
|
POST_HOC outcome
Timeframe: 28 daysPopulation: 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.
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
Outcome measures
| Measure |
Nitazoxanide
n=104 Participants
Two nitazoxanide 300 mg tablets orally twice daily for 5 days
|
Placebo
n=121 Participants
Two placebo tablets orally twice daily for 5 days
|
|---|---|---|
|
Progression to Severe COVID-19 for Subjects At Increased Risk Per CDC Guidelines
|
0.009 proportion of subjects
|
0.057 proportion of subjects
|
POST_HOC outcome
Timeframe: 28 daysPopulation: 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.
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
Outcome measures
| Measure |
Nitazoxanide
n=60 Participants
Two nitazoxanide 300 mg tablets orally twice daily for 5 days
|
Placebo
n=69 Participants
Two placebo tablets orally twice daily for 5 days
|
|---|---|---|
|
Progression to Severe COVID-19 in Subjects at High Risk by FDA Guidelines
|
0.016 proportion of subjects
|
0.086 proportion of subjects
|
Adverse Events
Nitazoxanide
Placebo
Serious adverse events
| Measure |
Nitazoxanide
n=472 participants at risk
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
|
Placebo
n=463 participants at risk
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
|
|---|---|---|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/472 • 28 days
|
0.22%
1/463 • Number of events 1 • 28 days
|
|
Infections and infestations
COVID-19
|
0.00%
0/472 • 28 days
|
0.22%
1/463 • Number of events 1 • 28 days
|
|
Infections and infestations
COVID-19 pneumonia
|
0.21%
1/472 • Number of events 1 • 28 days
|
0.65%
3/463 • Number of events 3 • 28 days
|
|
Infections and infestations
Diverticulitis
|
0.00%
0/472 • 28 days
|
0.22%
1/463 • Number of events 1 • 28 days
|
|
Nervous system disorders
Syncope
|
0.00%
0/472 • 28 days
|
0.22%
1/463 • Number of events 1 • 28 days
|
|
Respiratory, thoracic and mediastinal disorders
Aspiration
|
0.21%
1/472 • Number of events 1 • 28 days
|
0.00%
0/463 • 28 days
|
Other adverse events
| Measure |
Nitazoxanide
n=472 participants at risk
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
|
Placebo
n=463 participants at risk
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
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
3.4%
16/472 • Number of events 472 • 28 days
|
2.2%
10/463 • Number of events 463 • 28 days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place