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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 935 participants
• Primary outcome timeframe: Up to 21 days
• Results posted on: 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=5 Participants	40.7 years STANDARD_DEVIATION 14.68 • n=7 Participants	40.5 years STANDARD_DEVIATION 14.75 • n=5 Participants
Sex: Female, Male Female	282 Participants n=5 Participants	284 Participants n=7 Participants	566 Participants n=5 Participants
Sex: Female, Male Male	190 Participants n=5 Participants	179 Participants n=7 Participants	369 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	117 Participants n=5 Participants	112 Participants n=7 Participants	229 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	349 Participants n=5 Participants	343 Participants n=7 Participants	692 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	6 Participants n=5 Participants	8 Participants n=7 Participants	14 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Race (NIH/OMB) Black or African American	41 Participants n=5 Participants	43 Participants n=7 Participants	84 Participants n=5 Participants
Race (NIH/OMB) White	404 Participants n=5 Participants	388 Participants n=7 Participants	792 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	14 Participants n=5 Participants	19 Participants n=7 Participants	33 Participants n=5 Participants
Height	169.1 centimeters STANDARD_DEVIATION 10.84 • n=5 Participants	168.4 centimeters STANDARD_DEVIATION 9.96 • n=7 Participants	168.7 centimeters STANDARD_DEVIATION 10.41 • n=5 Participants
Weight	88.0 kilograms STANDARD_DEVIATION 24.44 • n=5 Participants	88.5 kilograms STANDARD_DEVIATION 23.36 • n=7 Participants	88.3 kilograms STANDARD_DEVIATION 23.90 • n=5 Participants
BMI	30.7 kilograms per meters squared STANDARD_DEVIATION 7.72 • n=5 Participants	31.1 kilograms per meters squared STANDARD_DEVIATION 7.51 • n=7 Participants	30.9 kilograms per meters squared STANDARD_DEVIATION 7.62 • n=5 Participants
Time from Onset of Symptoms to Randomization	41.5 hours STANDARD_DEVIATION 15.73 • n=5 Participants	41.9 hours STANDARD_DEVIATION 16.71 • n=7 Participants	41.7 hours STANDARD_DEVIATION 16.21 • n=5 Participants
Tobacco Use Current Tobacco User	115 Participants n=5 Participants	106 Participants n=7 Participants	221 Participants n=5 Participants
Tobacco Use Past Tobacco User	62 Participants n=5 Participants	69 Participants n=7 Participants	131 Participants n=5 Participants
Tobacco Use Never Used Tobacco	295 Participants n=5 Participants	288 Participants n=7 Participants	583 Participants n=5 Participants
Severity of Disease Mild Illness	301 Participants n=5 Participants	305 Participants n=7 Participants	606 Participants n=5 Participants
Severity of Disease Moderate Illness	170 Participants n=5 Participants	158 Participants n=7 Participants	328 Participants n=5 Participants
Severity of Disease Unknown	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Risk of Severe Illness At Increased Risk of Severe Illness	330 Participants n=5 Participants	338 Participants n=7 Participants	668 Participants n=5 Participants
Risk of Severe Illness Not At Increased Risk of Severe Illness	142 Participants n=5 Participants	125 Participants n=7 Participants	267 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 21 days

Population: 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 days

Population: 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 10

Population: 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 10

Population: 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 4	-0.70 log10 RNA copies/milliliter Standard Error 0.118	-1.02 log10 RNA copies/milliliter Standard Error 0.126
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

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days

Population: 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 days

Population: 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 days

Population: 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 days

Population: 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 days

Population: 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 days

Population: 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 days

Population: 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

Serious events: 2 serious events

Other events: 16 other events

Deaths: 2 deaths

Placebo

Serious events: 7 serious events

Other events: 10 other events

Deaths: 0 deaths

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

Sr. Director, Research Operations

Romark

Phone: 8132828544

Email: jessica.fulgencio@romark.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place