Trial Outcomes & Findings for 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 (NCT NCT04359680)

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1407 participants

Primary outcome timeframe

Up to 6 weeks

Results posted on

2024-06-26

Participant Flow

Participant milestones

Participant milestones
Measure	Nitazoxanide Two NTZ 300 mg tablets orally twice daily for 6 weeks	Placebo Two placebo tablets orally twice daily for 6 weeks
Overall Study STARTED	711	696
Overall Study COMPLETED	616	604
Overall Study NOT COMPLETED	95	92

Reasons for withdrawal

Reasons for withdrawal
Measure	Nitazoxanide Two NTZ 300 mg tablets orally twice daily for 6 weeks	Placebo Two placebo tablets orally twice daily for 6 weeks
Overall Study Withdrawal by Subject	29	24
Overall Study Adverse Event	6	2
Overall Study Lost to Follow-up	56	59
Overall Study Protocol Violation	3	5
Overall Study Physician Decision	1	1
Overall Study Sponsor Decision	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Nitazoxanide n=686 Participants Two NTZ 300 mg tablets orally twice daily for 6 weeks	Placebo n=663 Participants Two placebo tablets orally twice daily for 6 weeks	Total n=1349 Participants Total of all reporting groups
Age, Continuous	40 years STANDARD_DEVIATION 13.8 • n=5 Participants	40 years STANDARD_DEVIATION 13.8 • n=7 Participants	40 years STANDARD_DEVIATION 13.8 • n=5 Participants
Sex: Female, Male Female	410 Participants n=5 Participants	411 Participants n=7 Participants	821 Participants n=5 Participants
Sex: Female, Male Male	276 Participants n=5 Participants	252 Participants n=7 Participants	528 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	219 Participants n=5 Participants	219 Participants n=7 Participants	438 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	455 Participants n=5 Participants	429 Participants n=7 Participants	884 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	12 Participants n=5 Participants	15 Participants n=7 Participants	27 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	6 Participants n=5 Participants	0 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) Asian	33 Participants n=5 Participants	25 Participants n=7 Participants	58 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Black or African American	118 Participants n=5 Participants	123 Participants n=7 Participants	241 Participants n=5 Participants
Race (NIH/OMB) White	469 Participants n=5 Participants	469 Participants n=7 Participants	938 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	56 Participants n=5 Participants	45 Participants n=7 Participants	101 Participants n=5 Participants
Weight (kg)	84 kilograms STANDARD_DEVIATION 22.4 • n=5 Participants	85 kilograms STANDARD_DEVIATION 22.1 • n=7 Participants	84 kilograms STANDARD_DEVIATION 22.2 • n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Nitazoxanide n=629 Participants Two NTZ 300 mg tablets orally twice daily for 6 weeks	Placebo n=613 Participants Two placebo tablets orally twice daily for 6 weeks
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	0.02 proportion of participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Nitazoxanide n=629 Participants Two NTZ 300 mg tablets orally twice daily for 6 weeks	Placebo n=613 Participants Two placebo tablets orally twice daily for 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.	0.05 proportion of participants	0.05 proportion of participants

SECONDARY outcome

Timeframe: 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

Note: statistical analysis not performed because no events occurred.

Outcome measures

Outcome measures
Measure	Nitazoxanide n=629 Participants Two NTZ 300 mg tablets orally twice daily for 6 weeks	Placebo n=613 Participants Two placebo tablets orally twice daily for 6 weeks
Proportion Experiencing Mortality Due to COVID-19 or Complications Thereof	0 proportion of participants	0 proportion of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Nitazoxanide n=629 Participants Two NTZ 300 mg tablets orally twice daily for 6 weeks	Placebo n=613 Participants Two placebo tablets orally twice daily for 6 weeks
Proportion With Anti-SARS-CoV-2 Antibodies at Either of the Week 6 or Week 8 Visits	0.17 proportion of participants	0.19 proportion of participants

POST_HOC outcome

Timeframe: Up to 56 days

Population: Participants experiencing symptomatic COVID-19 during the study period

Descriptive statistics of the number of days patients with symptomatic COVID-19 report not being at usual health due to COVID-19

Outcome measures

Outcome measures
Measure	Nitazoxanide n=13 Participants Two NTZ 300 mg tablets orally twice daily for 6 weeks	Placebo n=13 Participants Two placebo tablets orally twice daily for 6 weeks
Days Not at Usual Health Due to COVID-19	13.2 days Standard Deviation 16.88	19.5 days Standard Deviation 14.58

POST_HOC outcome

Timeframe: Up to 56 days

Population: Patients with symptomatic 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

Outcome measures

Outcome measures
Measure	Nitazoxanide n=13 Participants Two NTZ 300 mg tablets orally twice daily for 6 weeks	Placebo n=13 Participants Two placebo tablets orally twice daily for 6 weeks
Days Unable to Perform Usual Activities Due to COVID-19	8.2 days Standard Deviation 11.73	16.5 days Standard Deviation 12.72

POST_HOC outcome

Timeframe: Up to 56 days

Population: Patients with symptomatic 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

Outcome measures

Outcome measures
Measure	Nitazoxanide n=13 Participants Two NTZ 300 mg tablets orally twice daily for 6 weeks	Placebo n=13 Participants Two placebo tablets orally twice daily for 6 weeks
Days Meeting Acute Respiratory Illness Symptom Severity Criteria Due to COVID-19	10.0 days Standard Deviation 15.52	13.8 days Standard Deviation 12.05

POST_HOC outcome

Timeframe: Up to 56 days

Population: Participants with symptomatic 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.

Outcome measures

Outcome measures
Measure	Nitazoxanide n=13 Participants Two NTZ 300 mg tablets orally twice daily for 6 weeks	Placebo n=13 Participants Two placebo tablets orally twice daily for 6 weeks
Maximum Symptom Severity Due to COVID-19	1.3 score on a scale Standard Deviation 0.95	2.3 score on a scale Standard Deviation 1.11

POST_HOC outcome

Timeframe: Up to 56 days

Population: Participants experiencing symptomatic viral respiratory illness

Descriptive statistics of the number of days patients with symptomatic viral respiratory illness (VRI) report not being at usual health due to VRI

Outcome measures

Outcome measures
Measure	Nitazoxanide n=29 Participants Two NTZ 300 mg tablets orally twice daily for 6 weeks	Placebo n=31 Participants Two placebo tablets orally twice daily for 6 weeks
Days Not At Usual Health Due to VRI	9.9 days Standard Deviation 12.19	14.4 days Standard Deviation 14.44

POST_HOC outcome

Timeframe: Up to 56 days

Population: Participants experiencing symptomatic viral respiratory illness (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

Outcome measures

Outcome measures
Measure	Nitazoxanide n=29 Participants Two NTZ 300 mg tablets orally twice daily for 6 weeks	Placebo n=31 Participants Two placebo tablets orally twice daily for 6 weeks
Days Unable to Perform Usual Activities Due to VRI	5.9 days Standard Deviation 8.85	9.7 days Standard Deviation 11.61

POST_HOC outcome

Timeframe: Up to 56 days

Population: Participants with symptomatic viral respiratory illness (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

Outcome measures

Outcome measures
Measure	Nitazoxanide n=29 Participants Two NTZ 300 mg tablets orally twice daily for 6 weeks	Placebo n=31 Participants Two placebo tablets orally twice daily for 6 weeks
Days Meeting Acute Respiratory Illness Symptom Severity Criteria Due to VRI	7.3 days Standard Deviation 10.97	11.4 days Standard Deviation 12.73

POST_HOC outcome

Timeframe: Up to 56 days

Population: Participants with symptomatic viral respiratory illness (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.

Outcome measures

Outcome measures
Measure	Nitazoxanide n=29 Participants Two NTZ 300 mg tablets orally twice daily for 6 weeks	Placebo n=31 Participants Two placebo tablets orally twice daily for 6 weeks
Maximum Symptom Severity Due to VRI	1.6 score on a scale Standard Deviation 0.98	1.9 score on a scale Standard Deviation 1.01

Adverse Events

Nitazoxanide

Serious events: 3 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 6 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Nitazoxanide n=686 participants at risk Two NTZ 300 mg tablets orally twice daily for 6 weeks	Placebo n=663 participants at risk Two placebo tablets orally twice daily for 6 weeks
Cardiac disorders Myocardial infarction	0.00% 0/686 • 8 weeks	0.15% 1/663 • Number of events 1 • 8 weeks
Cardiac disorders Syncope	0.00% 0/686 • 8 weeks	0.15% 1/663 • Number of events 1 • 8 weeks
Gastrointestinal disorders Abdominal hernia	0.15% 1/686 • Number of events 1 • 8 weeks	0.00% 0/663 • 8 weeks
Hepatobiliary disorders Cholelithiasis	0.00% 0/686 • 8 weeks	0.15% 1/663 • Number of events 1 • 8 weeks
Hepatobiliary disorders Drug-induced liver injury	0.15% 1/686 • Number of events 1 • 8 weeks	0.00% 0/663 • 8 weeks
Infections and infestations Epididymitis	0.00% 0/686 • 8 weeks	0.15% 1/663 • Number of events 1 • 8 weeks
Injury, poisoning and procedural complications Ankle fracture	0.15% 1/686 • Number of events 1 • 8 weeks	0.00% 0/663 • 8 weeks
Injury, poisoning and procedural complications Lower limb fracture	0.00% 0/686 • 8 weeks	0.15% 1/663 • Number of events 1 • 8 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine cancer	0.00% 0/686 • 8 weeks	0.15% 1/663 • Number of events 1 • 8 weeks

Other adverse events

Adverse event data not reported

Additional Information

Sr. Director, Research Operations

Romark, L.C.

Phone: 8132828544

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place