NTZ-SARI: Nitazoxanide Versus Placebo for the Treatment of Hospitalized Subjects With Severe Acute Respiratory Illness

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT02057757
• Collaborator: Mexican Emerging Infectious Diseases Clinical Research Network (Other)
• Enrollment: 260
• Locations: 6
• Arms: 2
• Duration (Months): 47
• Patients Per Site: 43.3
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

Respiratory viruses are a significant cause of hospitalization for respiratory tract infections. This study will evaluate the safety, effectiveness, and tolerability of nitazoxanide (NTZ) in treating severe acute respiratory illness (SARI) in people who are hospitalized.

Condition or Disease	Intervention/Treatment	Phase
Severe Acute Respiratory Illness	Drug: Nitazoxanide; Drug: Placebo	Phase 2

Detailed Description

Respiratory viral infections are one of the most common causes of illness in the world. These infections are major causes of SARI and can lead to severe outcomes, including hospitalization and death. NTZ is a medication that is approved in the United States and Mexico to treat gastrointestinal parasitic diseases. This study will evaluate the use of NTZ to treat SARI. The purpose of this study is to evaluate the safety, effectiveness, and tolerability of NTZ, in combination with standard care, in treating SARI in people who are hospitalized.

Participants will be hospitalized and study entry assessments will include medical assessments, blood collection, and a nasopharyngeal swab or wash. Participants will then be randomly assigned to receive NTZ or placebo for 5 days. Participants younger than 12 years will receive an oral suspension formulation of NTZ or placebo; participants 12 years and older will receive NTZ or placebo tablets. All participants will also receive standard of care treatment for acute severe viral respiratory infections, which may include antibiotics and/or treatment for influenza. They will be discharged from the hospital based on their doctors' recommendations. Participants will record their temperature and symptoms in a daily diary, which will be reviewed by study staff during study visits. Follow-up visits will occur on Days 3, 7, 14, and 28, and may occur as inpatient or outpatient visits. These visits may include the same assessments that occurred at baseline, as well as physical examinations, depending on the visit. Participants who are still hospitalized at Day 28 will be followed by study staff until they are discharged from the hospital.

Study Design

• Study Type: Interventional
• Actual Enrollment: 260 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized Double-Blind Phase 2 Study Comparing the Efficacy, Safety, and Tolerability of Nitazoxanide Versus Placebo in Addition to Standard Care for the Treatment of Hospitalized Subjects With Severe Acute Respiratory Illness
• Study Start Date: Feb 1, 2014
• Actual Primary Completion Date: May 1, 2017
• Actual Study Completion Date: Jan 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nitazoxanide (NTZ) Participants will receive NTZ for 5 days. Participants younger than 12 years will receive an oral suspension formulation of NTZ; participants 12 years and older will receive NTZ tablets.	Drug: Nitazoxanide; Participants 1 to 3 years old: 5 mL oral suspension (100 mg NTZ) every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL oral suspension (200 mg NTZ) every 12 hours for 5 days. Participants 12 years and older: two 300-mg NTZ tablets orally twice daily for 5 days.; Other Names: NTZ
Placebo Comparator: Placebo Participants will receive placebo for 5 days. Participants younger than 12 years will receive an oral suspension formulation of placebo; participants 12 years and older will receive placebo tablets.	Drug: Placebo; Participants 1 to 3 years old: 5 mL placebo oral suspension every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL placebo oral suspension every 12 hours for 5 days. Participants 12 years and older: two placebo tablets orally twice daily for 5 days.; Other Names: PCB

Outcome Measures

Primary Outcome Measures

1. Time to Hospital Discharge [Measured through Day 28]

   The time to hospital discharge measured through Day 28.

Secondary Outcome Measures

1. Number of Participants Hospitalized on Days 3, 7, 14, and 28 [Measured at Day 3, Day 7, Day 14, and Day 28]

   The number of study participants (e.g., adults and children) who were hospitalized on Days 3, 7, 14, and 28.

2. Number of Participants Who Died Within the First 5 Days [Measured within First 5 Days]

   Total Deaths of Participants, including Deaths within First 5 Days

3. Number of Participants Who Experienced Clinical Symptoms [Measured through Day 28]

   Measured daily through Study Day 14 and then again on Study Day 28

4. Duration of Fever in Study Participants [Measured each day through Day 14 and on Day 28]

   Study participants' duration (hours) of fever measured daily through Day 14 and then again on Day 28. The total duration in hours from the visit when fever was registered for the study participant until the next visit when no fever was registered for the study participant.

5. Number of Participants Who Require Oxygen Use [Measured through Day 28 or participants' last day of hospitalization]

   Number of study participants who require use of supplemental oxygen at time points (e.g., Any time, Day 0, Day 3, Day 7, Day 14, and Day 28)

6. Number of Study Participants (e.g., Adult and Children) Admitted to the Intensive Care Unit (ICU) by Time Point (Anytime, Day 0, Day 3, Day 7, Day 14, Day 28) [Measured through Day 28 or participants' last day in the ICU]

   Number of study participants (e.g., adult and children) admitted to the intensive care unit (ICU) by time point (Anytime, Day 0, Day 3, Day 7, Day 14, Day 28); worst case imputed.

7. Study Participants (e.g., Adults, Children) Requiring Mechanical Ventilation at Study Time Points (Any Time, Day 0, Day 3, Day 7, Day 14, Day 28) [Measured through Day 28 or participants' last day of hospitalization]

   Study participants (e.g., adults, children) requiring mechanical ventilation (e.g., intubation/extubation) at study time points (Any Time, Day 0, Day 3, Day 7, Day 14, Day 28); worst case imputed.

8. Number of Study Participants With the Presence of Complications (Pneumonia, Respiratory Failure Requiring Mechanical Ventilation, Acute Respiratory Distress Syndrome [ARDS], Sepsis, or Bronchiolitis) During Study [Measured through Day 28 or participants' last day of hospitalization]

   Number of study participants (e.g., adults and children) with the presence of a complication (pneumonia, respiratory failure requiring mechanical ventilation, acute respiratory distress syndrome [ARDS], sepsis, or bronchiolitis) during the study .

9. Duration (Days) Until Affirmative Global Assessment (e.g., Answered Yes) by Study Participants (e.g., Adults, Children) [Measured daily through Day 14 and on Day 28]

   Study participant (e.g., adults and children) answers (e.g., yes) to global assessment questions measured daily through Day 14 and then again on Day 28.

10. Number of Participants Using Antibiotics/Antivirals During Hospitalization [Measured through participants' first 5 days of hospitalization]

    Number of study participants taking an Antibiotic or Anti-Influenza Antiviral during first 5 days of hospitalization.

11. Number of Participants Who Are Re-hospitalized Within 28 Days [Measured through Day 28]

    Number of study participants (e.g., adults and children) who were re-hospitalized within 28 days (e.g., days from randomization).

12. Use of Systemic Corticosteroids [Measured within First 5 Days]

    Number of study participants taking Systemic Steroids during first 5 days.

13. Presence of Virus on Nasopharyngeal (NP) Swab at Day 3 (Same Virus as Day 0) [Measured through Day 3]

    Study participants with Detectable Virus on nasopharyngeal (NP) swab at Baseline and at Day 3.

14. Number of Participants Reporting Adverse Events (AEs) [Measured through Day 28 or participants' last day of hospitalization]

    Number of study participants with at least one Adverse Event During Study Duration

15. Number of Participants Reporting Serious Adverse Events (SAEs) [Measured through Day 28 or participants' last day of hospitalization]

    Number of study participants (e.g., adults and children) reporting at least one serious adverse events (SAEs).

16. Chemistry Laboratory Assessments (Creatinine, Total Bilirubin) on Days 3, 7, and 28 [Measured on Day 3, Day, 7 and Day 28]

    Laboratory values for chemistry laboratory assessments (e.g., Creatinine and Total Bilirubin) on Days 3, 7, and 28.

17. Chemistry Laboratory Assessments (ALT, AST, LDH) on Days 3, 7, and 28 [Measured on Day 3, Day 7, and Day 28]

    Chemistry laboratory assessments (e.g., ALT, AST, and LDH) on Days 3, 7, and 28.

18. Chemistry Laboratory Assessment (CRP) on Days 3, 7, and 28 [Measured on Day 3, Day, 7 and Day 28]

    Lab Values for chemistry laboratory assessment (e.g., CRP) on Days 3, 7, and 28.

19. Hematologic Laboratory Assessments (Neutrophils, Lymphocytes, Eosinophils, and Hematocrit) on Days 3, 7, and 28 [Measured on Day 3, Day, 7 and Day 28]

    Hematology laboratory assessments (e.g., Neutrophils, Lymphocytes, Eosinophils, and Hematocrit) on Days 3, 7, and 28.

20. Hematologic Laboratory Assessment (Hemoglobin) on Days 3, 7, and 28 [Measured on Day 3, Day, 7 and Day 28]

    Hematology laboratory assessment (e.g., Hemoglobin) on Days 3, 7, and 28.

21. Hematologic Laboratory Assessments (WBC, Platelets) on Days 3, 7, and 28 [Measured on Day 3, Day, 7 and Day 28]

    Lab values for hematology laboratory assessments (e.g., WBC and Platelets) on Days 3, 7, and 28.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Months and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Signed informed consent prior to performance or initiation of any study procedures

• Age greater than or equal to 12 months of age (no upper age limit)

• Influenza-like illness (ILI), defined as (all of the following):

• Onset of fever greater than or equal to 38°C (or hypothermia less than 36°C)

• New or worse cough or sore throat

• New or worse shortness of breath or difficulty breathing

• Onset of illness no more than 5 days before screening defined as when the participant experienced at least 1 respiratory symptom, constitutional symptom, or fever

• Hospitalization for ILI (decision for hospitalization will be up to the individual treating clinician), with anticipated hospitalization for more than 24 hours

• One of the following to avoid pregnancy:

• Females who are able to become pregnant (i.e., are not postmenopausal, have not undergone surgical sterilization, and are sexually active with men) must agree to use at least 1 effective form of contraception from the date of informed consent through Day 28 of study

• Males who have not undergone surgical sterilization and are sexually active with women must agree to use condoms or have a partner use at least 1 effective form of contraception through Day 28 of study

Exclusion Criteria:

• Women who are pregnant or breastfeeding

• Clinical suspicion that etiology of illness is primarily bacterial in origin

• Prior treatment with antivirals (e.g., oseltamivir) for the current illness for more than 24 hours

• Unable to take oral medications (adults must tolerate tablets, children must tolerate suspension)

• Unable to tolerate oral food/fluids (absorption is significantly better with food)

• Prior treatment with any investigational drug therapy within 30 days prior to screening

• Known sensitivity to NTZ or any of the excipients comprising the NTZ tablets

• Prior NTZ use within 1 week

• Self-reported history of chronic kidney disease or impaired renal function (no blood or urine kidney function laboratory testing will be done prior to enrollment, but intent is to exclude disease severe enough to cause estimated creatinine clearance [CrCl] less than 30)

• Self-reported history of liver disease (no blood laboratory testing will be done prior to enrollment, but intent is to exclude disease severe enough to cause cirrhosis or total bilirubin greater than 2, aspartate aminotransferase [AST]/alanine aminotransferase [ALT] greater than 3 times the upper limit of normal [ULN])

• Presence of any pre-existing illness that, in the opinion of the investigator, would place the participant at an unreasonably increased risk through participation in this study

• Participants who, in the judgment of the investigator, will be unlikely to comply with the requirements of this protocol

• The onset of SARI occurs after hospitalization

• Hospitalized for any reason for greater than 48 hours prior to enrollment

• Participants previously enrolled in this study

• Prior hospital discharge within 30 days

• Known chronic respiratory infection (e.g., tuberculosis, atypical mycobacterial infections)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Instituto Nacional de Pediatria	Coyoacan		Mexico	04530
2	Hospital General Dr. Aurelio Valdivieso	Oaxaca		Mexico	68050
3	Hospital Central Dr. Ignacio Morones Prieto	San Luis Potosi		Mexico	78240
4	Hospital Infantil de Mexico Federico Gomez	Tamaulipas		Mexico	06720
5	Instituto Nacional de Ciencias medicas y Nutricion Salvador Zubiran	Tlalpan		Mexico	14000
6	Instituto Nacional de Enfermedades Respiratorias	Tlalpan		Mexico	14000

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)
• Mexican Emerging Infectious Diseases Clinical Research Network

Investigators

• Study Chair: Lourdes Guerrero Almeida, M.D., Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
• Study Chair: Ana Gamiño, M.D., Hospital Infantil de Mexico Federico Gomez
• Principal Investigator: Arturo Galindo Fraga, M.D., Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
• Principal Investigator: Sarbelio Moreno, M.D., Hospital Infantil de Mexico Federico Gomez
• Principal Investigator: Javier Araujo Melendez, M.D., Hospital Central "Dr. Ignacio Morones Prieto"
• Principal Investigator: Alejandra Ramirez Venegas, M.D., Instituto Nacional de Enfermedades Respiratorias
• Principal Investigator: Beatriz Llamosas Gallardo, M.D., Instituto Nacional de Pediatria
• Principal Investigator: Yuri Roldan Aragon, M.D., Hospital General Dr. Aurelio Valdivies

Study Documents (Full-Text)

• Statistical Analysis Plan - Oct 17, 2017
• Study Protocol - Sep 12, 2016

More Information

Publications

None provided.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT02057757
• Other Study ID Numbers: NTZ-SARI
• First Posted: Feb 7, 2014
• Last Update Posted: Aug 1, 2018
• Last Verified: Jul 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Additional relevant MeSH terms: Nitazoxanide

Study Results

Participant Flow

Arm/Group Title	Nitazoxanide (NTZ)	Placebo
Arm/Group Description	Participants will receive NTZ for 5 days. Participants younger than 12 years will receive an oral suspension formulation of NTZ; participants 12 years and older will receive NTZ tablets. Nitazoxanide (NTZ): Participants 1 to 3 years old: 5 mL oral suspension (100 mg NTZ) every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL oral suspension (200 mg NTZ) every 12 hours for 5 days. Participants 12 years and older: two 300-mg NTZ tablets orally twice daily for 5 days.	Participants will receive placebo for 5 days. Participants younger than 12 years will receive an oral suspension formulation of placebo; participants 12 years and older will receive placebo tablets. Placebo: Participants 1 to 3 years old: 5 mL placebo oral suspension every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL placebo oral suspension every 12 hours for 5 days. Participants 12 years and older: two placebo tablets orally twice daily for 5 days.
Period Title: Overall Study
STARTED	131	129
Intent to Treat	130	127
COMPLETED	117	121
NOT COMPLETED	14	8

Baseline Characteristics

Arm/Group Title	Nitazoxanide (NTZ)	Placebo	Total
Arm/Group Description	Participants will receive NTZ for 5 days. Participants younger than 12 years will receive an oral suspension formulation of NTZ; participants 12 years and older will receive NTZ tablets. Nitazoxanide (NTZ): Participants 1 to 3 years old: 5 mL oral suspension (100 mg NTZ) every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL oral suspension (200 mg NTZ) every 12 hours for 5 days. Participants 12 years and older: two 300-mg NTZ tablets orally twice daily for 5 days.	Participants will receive placebo for 5 days. Participants younger than 12 years will receive an oral suspension formulation of placebo; participants 12 years and older will receive placebo tablets. Placebo: Participants 1 to 3 years old: 5 mL placebo oral suspension every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL placebo oral suspension every 12 hours for 5 days. Participants 12 years and older: two placebo tablets orally twice daily for 5 days.	Total of all reporting groups
Overall Participants	130	127	257
Age (Count of Participants)
<=18 years	67 51.5%	64 50.4%	131 51%
Between 18 and 65 years	54 41.5%	56 44.1%	110 42.8%
>=65 years	9 6.9%	7 5.5%	16 6.2%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	22.6 (24.0)	23.6 (24.4)	23.1 (24.2)
Sex: Female, Male (Count of Participants)
Female	68 52.3%	50 39.4%	118 45.9%
Male	62 47.7%	77 60.6%	139 54.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	130 100%	127 100%	257 100%
Not Hispanic or Latino	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	1 0.8%	0 0%	1 0.4%
More than one race	129 99.2%	127 100%	256 99.6%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Mexico	130 100%	127 100%	257 100%
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	27.2 (6.2)	27.0 (5.6)	27.1 (5.9)
BMI Z Score (Z Score) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Z Score]	0.2 (2.0)	-0.6 (2.5)	-0.2 (2.3)

Outcome Measures

1. Primary Outcome

Title	Time to Hospital Discharge
Description	The time to hospital discharge measured through Day 28.
Time Frame	Measured through Day 28

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nitazoxanide (NTZ)	Placebo
Arm/Group Description	Participants will receive NTZ for 5 days. Participants younger than 12 years will receive an oral suspension formulation of NTZ; participants 12 years and older will receive NTZ tablets. Nitazoxanide (NTZ): Participants 1 to 3 years old: 5 mL oral suspension (100 mg NTZ) every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL oral suspension (200 mg NTZ) every 12 hours for 5 days. Participants 12 years and older: two 300-mg NTZ tablets orally twice daily for 5 days.	Participants will receive placebo for 5 days. Participants younger than 12 years will receive an oral suspension formulation of placebo; participants 12 years and older will receive placebo tablets. Placebo: Participants 1 to 3 years old: 5 mL placebo oral suspension every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL placebo oral suspension every 12 hours for 5 days. Participants 12 years and older: two placebo tablets orally twice daily for 5 days.
Measure Participants	130	127
Mean (Standard Error) [Days]	7.1 (0.37)	7.5 (0.41)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nitazoxanide (NTZ), Placebo
	Comments
	Type of Statistical Test	Equivalence
	Comments	The equivalence margin is 1.25 Days.
Statistical Test of Hypothesis	p-Value	0.5634
	Comments
	Method	Fay - Shaw
	Comments

2. Secondary Outcome

Title	Number of Participants Hospitalized on Days 3, 7, 14, and 28
Description	The number of study participants (e.g., adults and children) who were hospitalized on Days 3, 7, 14, and 28.
Time Frame	Measured at Day 3, Day 7, Day 14, and Day 28

Outcome Measure Data

Analysis Population Description

Number of study participants - adults (>= 18 years) and children (< 18 years) in the Intent-to-Treat population (ITT) hospitalized by time point

Arm/Group Title	Nitazoxanide (NTZ)	Placebo
Arm/Group Description	Participants will receive NTZ for 5 days. Participants younger than 12 years will receive an oral suspension formulation of NTZ; participants 12 years and older will receive NTZ tablets. Nitazoxanide (NTZ): Participants 1 to 3 years old: 5 mL oral suspension (100 mg NTZ) every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL oral suspension (200 mg NTZ) every 12 hours for 5 days. Participants 12 years and older: two 300-mg NTZ tablets orally twice daily for 5 days.	Participants will receive placebo for 5 days. Participants younger than 12 years will receive an oral suspension formulation of placebo; participants 12 years and older will receive placebo tablets. Placebo: Participants 1 to 3 years old: 5 mL placebo oral suspension every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL placebo oral suspension every 12 hours for 5 days. Participants 12 years and older: two placebo tablets orally twice daily for 5 days.
Measure Participants	130	127
Day 3	95 73.1%	96 75.6%
Day 7	39 30%	38 29.9%
Day 14	7 5.4%	6 4.7%
Day 28	3 2.3%	2 1.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nitazoxanide (NTZ), Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.645
	Comments	The p-value for each time point was calculated; Day 3
	Method	Fay - Shaw
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Nitazoxanide (NTZ), Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.989
	Comments	The p-value for each value was calculated (Day 7).
	Method	Fay-Shaw
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Nitazoxanide (NTZ), Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.809
	Comments	Day 14
	Method	Fay-Shaw
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Nitazoxanide (NTZ), Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.671
	Comments	Day 28
	Method	Fay-Shaw
	Comments

3. Secondary Outcome

Title	Number of Participants Who Died Within the First 5 Days
Description	Total Deaths of Participants, including Deaths within First 5 Days
Time Frame	Measured within First 5 Days

Outcome Measure Data

Analysis Population Description

The Adult (>=18 Years) population includes 126 participants (63 in NTZ arm; 63 in Placebo arm). The Children (<18 Years) population includes 131 participants (67 in NTZ arm; 64 in Placebo arm)

Arm/Group Title	Nitazoxanide (NTZ)	Placebo
Arm/Group Description	Participants will receive NTZ for 5 days. Participants younger than 12 years will receive an oral suspension formulation of NTZ; participants 12 years and older will receive NTZ tablets. Nitazoxanide (NTZ): Participants 1 to 3 years old: 5 mL oral suspension (100 mg NTZ) every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL oral suspension (200 mg NTZ) every 12 hours for 5 days. Participants 12 years and older: two 300-mg NTZ tablets orally twice daily for 5 days.	Participants will receive placebo for 5 days. Participants younger than 12 years will receive an oral suspension formulation of placebo; participants 12 years and older will receive placebo tablets. Placebo: Participants 1 to 3 years old: 5 mL placebo oral suspension every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL placebo oral suspension every 12 hours for 5 days. Participants 12 years and older: two placebo tablets orally twice daily for 5 days.
Measure Participants	130	127
Total Deaths	2 1.5%	1 0.8%
Deaths within the First 5 Days (Adults >=18) Years	0 0%	0 0%
Deaths within the First 5 Days (Children<18) Years	0 0%	0 0%

4. Secondary Outcome

Title	Number of Participants Who Experienced Clinical Symptoms
Description	Measured daily through Study Day 14 and then again on Study Day 28
Time Frame	Measured through Day 28

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nitazoxanide (NTZ)	Placebo
Arm/Group Description	Participants will receive NTZ for 5 days. Participants younger than 12 years will receive an oral suspension formulation of NTZ; participants 12 years and older will receive NTZ tablets. Nitazoxanide (NTZ): Participants 1 to 3 years old: 5 mL oral suspension (100 mg NTZ) every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL oral suspension (200 mg NTZ) every 12 hours for 5 days. Participants 12 years and older: two 300-mg NTZ tablets orally twice daily for 5 days.	Participants will receive placebo for 5 days. Participants younger than 12 years will receive an oral suspension formulation of placebo; participants 12 years and older will receive placebo tablets. Placebo: Participants 1 to 3 years old: 5 mL placebo oral suspension every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL placebo oral suspension every 12 hours for 5 days. Participants 12 years and older: two placebo tablets orally twice daily for 5 days.
Measure Participants	130	127
Cough	71 54.6%	75 59.1%
Sore Throat	29 22.3%	23 18.1%
Fatigue	60 46.2%	54 42.5%
Nasal Discharge	40 30.8%	25 19.7%
Difficulty Breathing	54 41.5%	51 40.2%
Headache	21 16.2%	13 10.2%
Muscle Pain	28 21.5%	18 14.2%
Nausea	4 3.1%	8 6.3%
Vomiting	5 3.8%	7 5.5%
Diarrhea	4 3.1%	5 3.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nitazoxanide (NTZ), Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4277
	Comments	Cough
	Method	Fay - Shaw
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Nitazoxanide (NTZ), Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4022
	Comments	Sore Throat
	Method	Fay-Shaw
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Nitazoxanide (NTZ), Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5957
	Comments	Fatigue
	Method	Fay-Shaw
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Nitazoxanide (NTZ), Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0446
	Comments	Nasal Discharge
	Method	Fay-Shaw
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Nitazoxanide (NTZ), Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8628
	Comments	Difficulty Breathing
	Method	Fay-Shaw
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Nitazoxanide (NTZ), Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.16
	Comments	Headache
	Method	Fay-Shaw
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Nitazoxanide (NTZ), Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1234
	Comments	Muscle Pain
	Method	Fay-Shaw
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Nitazoxanide (NTZ), Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2155
	Comments	Nausea
	Method	Fay-Shaw
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Nitazoxanide (NTZ), Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5176
	Comments	Vomiting
	Method	Fay-Shaw
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Nitazoxanide (NTZ), Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6986
	Comments	Diarrhea
	Method	Fay-Shaw
	Comments

5. Secondary Outcome

Title	Duration of Fever in Study Participants
Description	Study participants' duration (hours) of fever measured daily through Day 14 and then again on Day 28. The total duration in hours from the visit when fever was registered for the study participant until the next visit when no fever was registered for the study participant.
Time Frame	Measured each day through Day 14 and on Day 28

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nitazoxanide (NTZ)	Placebo
Arm/Group Description	Participants will receive NTZ for 5 days. Participants younger than 12 years will receive an oral suspension formulation of NTZ; participants 12 years and older will receive NTZ tablets. Nitazoxanide (NTZ): Participants 1 to 3 years old: 5 mL oral suspension (100 mg NTZ) every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL oral suspension (200 mg NTZ) every 12 hours for 5 days. Participants 12 years and older: two 300-mg NTZ tablets orally twice daily for 5 days.	Participants will receive placebo for 5 days. Participants younger than 12 years will receive an oral suspension formulation of placebo; participants 12 years and older will receive placebo tablets. Placebo: Participants 1 to 3 years old: 5 mL placebo oral suspension every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL placebo oral suspension every 12 hours for 5 days. Participants 12 years and older: two placebo tablets orally twice daily for 5 days.
Measure Participants	130	127
Mean (Standard Error) [hours]	11.3 (3.55)	20.6 (5.44)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nitazoxanide (NTZ), Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9850
	Comments
	Method	Fay - Shaw
	Comments

6. Secondary Outcome

Title	Number of Participants Who Require Oxygen Use
Description	Number of study participants who require use of supplemental oxygen at time points (e.g., Any time, Day 0, Day 3, Day 7, Day 14, and Day 28)
Time Frame	Measured through Day 28 or participants' last day of hospitalization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nitazoxanide (NTZ)	Placebo
Arm/Group Description	Participants will receive NTZ for 5 days. Participants younger than 12 years will receive an oral suspension formulation of NTZ; participants 12 years and older will receive NTZ tablets. Nitazoxanide (NTZ): Participants 1 to 3 years old: 5 mL oral suspension (100 mg NTZ) every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL oral suspension (200 mg NTZ) every 12 hours for 5 days. Participants 12 years and older: two 300-mg NTZ tablets orally twice daily for 5 days.	Participants will receive placebo for 5 days. Participants younger than 12 years will receive an oral suspension formulation of placebo; participants 12 years and older will receive placebo tablets. Placebo: Participants 1 to 3 years old: 5 mL placebo oral suspension every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL placebo oral suspension every 12 hours for 5 days. Participants 12 years and older: two placebo tablets orally twice daily for 5 days.
Measure Participants	130	127
Any Time	119 91.5%	118 92.9%
Day 0	114 87.7%	116 91.3%
Day 3	74 56.9%	80 63%
Day 7	28 21.5%	27 21.3%
Day 14	6 4.6%	5 3.9%
Day 28	6 4.6%	4 3.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nitazoxanide (NTZ), Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.681
	Comments	Any Time
	Method	Fay - Shaw
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Nitazoxanide (NTZ), Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.341
	Comments	Day 0
	Method	Fay-Shaw
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Nitazoxanide (NTZ), Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.321
	Comments	Day 3
	Method	Fay-Shaw
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Nitazoxanide (NTZ), Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.957
	Comments	Day 7
	Method	Fay-Shaw
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Nitazoxanide (NTZ), Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.788
	Comments	Day 14
	Method	Fay-Shaw
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Nitazoxanide (NTZ), Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.544
	Comments	Day 28
	Method	Fay-Shaw
	Comments

7. Secondary Outcome

Title	Number of Study Participants (e.g., Adult and Children) Admitted to the Intensive Care Unit (ICU) by Time Point (Anytime, Day 0, Day 3, Day 7, Day 14, Day 28)
Description	Number of study participants (e.g., adult and children) admitted to the intensive care unit (ICU) by time point (Anytime, Day 0, Day 3, Day 7, Day 14, Day 28); worst case imputed.
Time Frame	Measured through Day 28 or participants' last day in the ICU

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nitazoxanide (NTZ)	Placebo
Arm/Group Description	Participants will receive NTZ for 5 days. Participants younger than 12 years will receive an oral suspension formulation of NTZ; participants 12 years and older will receive NTZ tablets. Nitazoxanide (NTZ): Participants 1 to 3 years old: 5 mL oral suspension (100 mg NTZ) every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL oral suspension (200 mg NTZ) every 12 hours for 5 days. Participants 12 years and older: two 300-mg NTZ tablets orally twice daily for 5 days.	Participants will receive placebo for 5 days. Participants younger than 12 years will receive an oral suspension formulation of placebo; participants 12 years and older will receive placebo tablets. Placebo: Participants 1 to 3 years old: 5 mL placebo oral suspension every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL placebo oral suspension every 12 hours for 5 days. Participants 12 years and older: two placebo tablets orally twice daily for 5 days.
Measure Participants	130	127
Any Time	3 2.3%	2 1.6%
Day 0	3 2.3%	1 0.8%
Day 3	1 0.8%	1 0.8%
Day 7	1 0.8%	1 0.8%
Day 14	0 0%	1 0.8%
Day 28	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nitazoxanide (NTZ), Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.671
	Comments	Any Time
	Method	Fay - Shaw
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Nitazoxanide (NTZ), Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.325
	Comments	Day 0
	Method	Fay-Shaw
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Nitazoxanide (NTZ), Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.987
	Comments	Day 3
	Method	Fay-Shaw
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Nitazoxanide (NTZ), Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.987
	Comments	Day 7
	Method	Fay-Shaw
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Nitazoxanide (NTZ), Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.311
	Comments	Day 14
	Method	Fay-Shaw
	Comments

8. Secondary Outcome

Title	Study Participants (e.g., Adults, Children) Requiring Mechanical Ventilation at Study Time Points (Any Time, Day 0, Day 3, Day 7, Day 14, Day 28)
Description	Study participants (e.g., adults, children) requiring mechanical ventilation (e.g., intubation/extubation) at study time points (Any Time, Day 0, Day 3, Day 7, Day 14, Day 28); worst case imputed.
Time Frame	Measured through Day 28 or participants' last day of hospitalization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nitazoxanide (NTZ)	Placebo
Arm/Group Description	Participants will receive NTZ for 5 days. Participants younger than 12 years will receive an oral suspension formulation of NTZ; participants 12 years and older will receive NTZ tablets. Nitazoxanide (NTZ): Participants 1 to 3 years old: 5 mL oral suspension (100 mg NTZ) every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL oral suspension (200 mg NTZ) every 12 hours for 5 days. Participants 12 years and older: two 300-mg NTZ tablets orally twice daily for 5 days.	Participants will receive placebo for 5 days. Participants younger than 12 years will receive an oral suspension formulation of placebo; participants 12 years and older will receive placebo tablets. Placebo: Participants 1 to 3 years old: 5 mL placebo oral suspension every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL placebo oral suspension every 12 hours for 5 days. Participants 12 years and older: two placebo tablets orally twice daily for 5 days.
Measure Participants	130	127
Any Time	4 3.1%	4 3.1%
Day 0	2 1.5%	1 0.8%
Day 3	1 0.8%	2 1.6%
Day 7	1 0.8%	1 0.8%
Day 14	1 0.8%	1 0.8%
Day 28	1 0.8%	1 0.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nitazoxanide (NTZ), Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.973
	Comments	Any Time
	Method	Fay - Shaw
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Nitazoxanide (NTZ), Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.575
	Comments	Day 0
	Method	Fay-Shaw
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Nitazoxanide (NTZ), Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.548
	Comments	Day 3
	Method	Fay-Shaw
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Nitazoxanide (NTZ), Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.987
	Comments	Day 7
	Method	Fay-Shaw
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Nitazoxanide (NTZ), Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.987
	Comments	Day 14
	Method	Fay-Shaw
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Nitazoxanide (NTZ), Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.987
	Comments	Day 28
	Method	Fay-Shaw
	Comments

9. Secondary Outcome

Title	Number of Study Participants With the Presence of Complications (Pneumonia, Respiratory Failure Requiring Mechanical Ventilation, Acute Respiratory Distress Syndrome [ARDS], Sepsis, or Bronchiolitis) During Study
Description	Number of study participants (e.g., adults and children) with the presence of a complication (pneumonia, respiratory failure requiring mechanical ventilation, acute respiratory distress syndrome [ARDS], sepsis, or bronchiolitis) during the study .
Time Frame	Measured through Day 28 or participants' last day of hospitalization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nitazoxanide (NTZ)	Placebo
Arm/Group Description	Participants will receive NTZ for 5 days. Participants younger than 12 years will receive an oral suspension formulation of NTZ; participants 12 years and older will receive NTZ tablets. Nitazoxanide (NTZ): Participants 1 to 3 years old: 5 mL oral suspension (100 mg NTZ) every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL oral suspension (200 mg NTZ) every 12 hours for 5 days. Participants 12 years and older: two 300-mg NTZ tablets orally twice daily for 5 days.	Participants will receive placebo for 5 days. Participants younger than 12 years will receive an oral suspension formulation of placebo; participants 12 years and older will receive placebo tablets. Placebo: Participants 1 to 3 years old: 5 mL placebo oral suspension every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL placebo oral suspension every 12 hours for 5 days. Participants 12 years and older: two placebo tablets orally twice daily for 5 days.
Measure Participants	130	127
Pneumonia	74 56.9%	73 57.5%
Respiratory Failure Requiring Mechanical Vent.	0 0%	0 0%
Acute Respiratory Distress Syndrome (ARDS)	6 4.6%	6 4.7%
Sepsis	0 0%	0 0%
Bronchitis	2 1.5%	7 5.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nitazoxanide (NTZ), Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.928
	Comments	Pneumonia
	Method	Fay - Shaw
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Nitazoxanide (NTZ), Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9669
	Comments	ARDS
	Method	Fay-Shaw
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Nitazoxanide (NTZ), Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0832
	Comments	Bronchitis
	Method	Fay-Shaw
	Comments

10. Secondary Outcome

Title	Duration (Days) Until Affirmative Global Assessment (e.g., Answered Yes) by Study Participants (e.g., Adults, Children)
Description	Study participant (e.g., adults and children) answers (e.g., yes) to global assessment questions measured daily through Day 14 and then again on Day 28.
Time Frame	Measured daily through Day 14 and on Day 28

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nitazoxanide (NTZ) - Adults >=18 Years	Placebo - Adults >=18 Years	Nitazoxanide (NTZ) - Children <18 Years	Placebo - Children <18 Years
Arm/Group Description	Participants will receive NTZ for 5 days. Participants younger than 12 years will receive an oral suspension formulation of NTZ; participants 12 years and older will receive NTZ tablets. Nitazoxanide (NTZ): Participants 1 to 3 years old: 5 mL oral suspension (100 mg NTZ) every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL oral suspension (200 mg NTZ) every 12 hours for 5 days. Participants 12 years and older: two 300-mg NTZ tablets orally twice daily for 5 days.	Participants will receive placebo for 5 days. Participants younger than 12 years will receive an oral suspension formulation of placebo; participants 12 years and older will receive placebo tablets. Placebo: Participants 1 to 3 years old: 5 mL placebo oral suspension every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL placebo oral suspension every 12 hours for 5 days. Participants 12 years and older: two placebo tablets orally twice daily for 5 days.	Participants will receive NTZ for 5 days. Participants younger than 12 years will receive an oral suspension formulation of NTZ; participants 12 years and older will receive NTZ tablets. Nitazoxanide (NTZ): Participants 1 to 3 years old: 5 mL oral suspension (100 mg NTZ) every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL oral suspension (200 mg NTZ) every 12 hours for 5 days. Participants 12 years and older: two 300-mg NTZ tablets orally twice daily for 5 days.	Participants will receive placebo for 5 days. Participants younger than 12 years will receive an oral suspension formulation of placebo; participants 12 years and older will receive placebo tablets. Placebo: Participants 1 to 3 years old: 5 mL placebo oral suspension every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL placebo oral suspension every 12 hours for 5 days. Participants 12 years and older: two placebo tablets orally twice daily for 5 days.
Measure Participants	63	63	67	64
Have you felt as good as you did before?	10.2 (1.47)	7.0 (1.27)	3.3 (0.40)	3.5 (0.63)
Are you functioning as well as you were before?	12.6 (1.52)	9.4 (1.38)	3.6 (0.43)	3.1 (0.36)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nitazoxanide (NTZ), Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0360
	Comments	Adults (>= 18 Years ) - Global Assessment: Have you felt as good as you did before you had the respiratory illness?
	Method	Fay - Shaw
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Nitazoxanide (NTZ), Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0380
	Comments	Adults (>= 18 Years) - Global Assessment: Are you functioning as well as you were before you had the respiratory illness?
	Method	Fay-Shaw
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Nitazoxanide (NTZ) - Children <18 Years, Placebo - Children <18 Years
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5035
	Comments	Children (< 18 Years) - Global Assessment: Have you/your child felt as good as you did before you had the respiratory illness?
	Method	Fay-Shaw
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Nitazoxanide (NTZ) - Children <18 Years, Placebo - Children <18 Years
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9231
	Comments	Children (<18 Years) - Global Assessment: Are you/your child functioning as well as you/your child were before you/your child had the respiratory illness?
	Method	Fay-Shaw
	Comments

11. Secondary Outcome

Title	Number of Participants Using Antibiotics/Antivirals During Hospitalization
Description	Number of study participants taking an Antibiotic or Anti-Influenza Antiviral during first 5 days of hospitalization.
Time Frame	Measured through participants' first 5 days of hospitalization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nitazoxanide (NTZ)	Placebo
Arm/Group Description	Participants will receive NTZ for 5 days. Participants younger than 12 years will receive an oral suspension formulation of NTZ; participants 12 years and older will receive NTZ tablets. Nitazoxanide (NTZ): Participants 1 to 3 years old: 5 mL oral suspension (100 mg NTZ) every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL oral suspension (200 mg NTZ) every 12 hours for 5 days. Participants 12 years and older: two 300-mg NTZ tablets orally twice daily for 5 days.	Participants will receive placebo for 5 days. Participants younger than 12 years will receive an oral suspension formulation of placebo; participants 12 years and older will receive placebo tablets. Placebo: Participants 1 to 3 years old: 5 mL placebo oral suspension every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL placebo oral suspension every 12 hours for 5 days. Participants 12 years and older: two placebo tablets orally twice daily for 5 days.
Measure Participants	130	127
Antibiotic Use During First 5 Days of Hosp	100 76.9%	88 69.3%
Antiviral Use During First 5 Days of Hosp	46 35.4%	45 35.4%

12. Secondary Outcome

Title	Number of Participants Who Are Re-hospitalized Within 28 Days
Description	Number of study participants (e.g., adults and children) who were re-hospitalized within 28 days (e.g., days from randomization).
Time Frame	Measured through Day 28

Outcome Measure Data

Analysis Population Description

The Adult (>=18 Years) population includes 126 participants (63 in NTZ arm; 63 in Placebo arm). The Children (<18 Years) population includes 131 participants (67 in NTZ arm; 64 in Placebo arm)

Arm/Group Title	Nitazoxanide (NTZ)	Placebo
Arm/Group Description	Participants will receive NTZ for 5 days. Participants younger than 12 years will receive an oral suspension formulation of NTZ; participants 12 years and older will receive NTZ tablets. Nitazoxanide (NTZ): Participants 1 to 3 years old: 5 mL oral suspension (100 mg NTZ) every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL oral suspension (200 mg NTZ) every 12 hours for 5 days. Participants 12 years and older: two 300-mg NTZ tablets orally twice daily for 5 days.	Participants will receive placebo for 5 days. Participants younger than 12 years will receive an oral suspension formulation of placebo; participants 12 years and older will receive placebo tablets. Placebo: Participants 1 to 3 years old: 5 mL placebo oral suspension every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL placebo oral suspension every 12 hours for 5 days. Participants 12 years and older: two placebo tablets orally twice daily for 5 days.
Measure Participants	130	127
Adults >=18 Years	1 0.8%	2 1.6%
Children >18 Years	1 0.8%	2 1.6%

13. Secondary Outcome

Title	Use of Systemic Corticosteroids
Description	Number of study participants taking Systemic Steroids during first 5 days.
Time Frame	Measured within First 5 Days

Outcome Measure Data

Analysis Population Description

The analysis was based on the Intent to Treat (ITT) population.

Arm/Group Title	Nitazoxanide (NTZ)	Placebo
Arm/Group Description	Participants will receive NTZ for 5 days. Participants younger than 12 years will receive an oral suspension formulation of NTZ; participants 12 years and older will receive NTZ tablets. Nitazoxanide (NTZ): Participants 1 to 3 years old: 5 mL oral suspension (100 mg NTZ) every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL oral suspension (200 mg NTZ) every 12 hours for 5 days. Participants 12 years and older: two 300-mg NTZ tablets orally twice daily for 5 days.	Participants will receive placebo for 5 days. Participants younger than 12 years will receive an oral suspension formulation of placebo; participants 12 years and older will receive placebo tablets. Placebo: Participants 1 to 3 years old: 5 mL placebo oral suspension every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL placebo oral suspension every 12 hours for 5 days. Participants 12 years and older: two placebo tablets orally twice daily for 5 days.
Measure Participants	130	127
Subjects Taking Systemic Steroids - First 5 Days	78 60%	70 55.1%
DESMOPRESSIN	0 0%	1 0.8%
DEXAMETHASONE	4 3.1%	5 3.9%
GLUCOCORTICOIDS (Fluticasone/Vilanterol)	0 0%	1 0.8%
HYDROCORTISONE	5 3.8%	3 2.4%
LEVOTHYROXINE	6 4.6%	8 6.3%
LEVOTHYROXINE SODIUM	1 0.8%	1 0.8%
METHYLPREDNISOLONE	35 26.9%	26 20.5%
NOVOTHYRAL	0 0%	1 0.8%
PREDNISONE	43 33.1%	35 27.6%

14. Secondary Outcome

Title	Presence of Virus on Nasopharyngeal (NP) Swab at Day 3 (Same Virus as Day 0)
Description	Study participants with Detectable Virus on nasopharyngeal (NP) swab at Baseline and at Day 3.
Time Frame	Measured through Day 3

Outcome Measure Data

Analysis Population Description

Efficacy analysis of Intent to Treat population

Arm/Group Title	Nitazoxanide (NTZ)	Placebo
Arm/Group Description	Participants will receive NTZ for 5 days. Participants younger than 12 years will receive an oral suspension formulation of NTZ; participants 12 years and older will receive NTZ tablets. Nitazoxanide (NTZ): Participants 1 to 3 years old: 5 mL oral suspension (100 mg NTZ) every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL oral suspension (200 mg NTZ) every 12 hours for 5 days. Participants 12 years and older: two 300-mg NTZ tablets orally twice daily for 5 days.	Participants will receive placebo for 5 days. Participants younger than 12 years will receive an oral suspension formulation of placebo; participants 12 years and older will receive placebo tablets. Placebo: Participants 1 to 3 years old: 5 mL placebo oral suspension every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL placebo oral suspension every 12 hours for 5 days. Participants 12 years and older: two placebo tablets orally twice daily for 5 days.
Measure Participants	79	89
No Detectable Virus on Day 3	17 13.1%	19 15%
Same Detectable Virus on Day 3	56 43.1%	61 48%
Different Detectable Virus on Day 3	6 4.6%	9 7.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nitazoxanide (NTZ), Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9785
	Comments	No Detectable Virus on Day 3
	Method	Fay-Shaw
	Comments

15. Secondary Outcome

Title	Number of Participants Reporting Adverse Events (AEs)
Description	Number of study participants with at least one Adverse Event During Study Duration
Time Frame	Measured through Day 28 or participants' last day of hospitalization

Outcome Measure Data

Analysis Population Description

Analysis was based on the safety population.

Arm/Group Title	Nitazoxanide (NTZ)	Placebo
Arm/Group Description	Participants will receive NTZ for 5 days. Participants younger than 12 years will receive an oral suspension formulation of NTZ; participants 12 years and older will receive NTZ tablets. Nitazoxanide (NTZ): Participants 1 to 3 years old: 5 mL oral suspension (100 mg NTZ) every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL oral suspension (200 mg NTZ) every 12 hours for 5 days. Participants 12 years and older: two 300-mg NTZ tablets orally twice daily for 5 days.	Participants will receive placebo for 5 days. Participants younger than 12 years will receive an oral suspension formulation of placebo; participants 12 years and older will receive placebo tablets. Placebo: Participants 1 to 3 years old: 5 mL placebo oral suspension every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL placebo oral suspension every 12 hours for 5 days. Participants 12 years and older: two placebo tablets orally twice daily for 5 days.
Measure Participants	130	127
Count of Participants [Participants]	83 63.8%	80 63%

16. Secondary Outcome

Title	Number of Participants Reporting Serious Adverse Events (SAEs)
Description	Number of study participants (e.g., adults and children) reporting at least one serious adverse events (SAEs).
Time Frame	Measured through Day 28 or participants' last day of hospitalization

Outcome Measure Data

Analysis Population Description

The analysis is based on the safety population.

Arm/Group Title	Nitazoxanide (NTZ)	Placebo
Arm/Group Description	Participants will receive NTZ for 5 days. Participants younger than 12 years will receive an oral suspension formulation of NTZ; participants 12 years and older will receive NTZ tablets. Nitazoxanide (NTZ): Participants 1 to 3 years old: 5 mL oral suspension (100 mg NTZ) every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL oral suspension (200 mg NTZ) every 12 hours for 5 days. Participants 12 years and older: two 300-mg NTZ tablets orally twice daily for 5 days.	Participants will receive placebo for 5 days. Participants younger than 12 years will receive an oral suspension formulation of placebo; participants 12 years and older will receive placebo tablets. Placebo: Participants 1 to 3 years old: 5 mL placebo oral suspension every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL placebo oral suspension every 12 hours for 5 days. Participants 12 years and older: two placebo tablets orally twice daily for 5 days.
Measure Participants	130	127
Count of Participants [Participants]	6 4.6%	3 2.4%

17. Secondary Outcome

Title	Chemistry Laboratory Assessments (Creatinine, Total Bilirubin) on Days 3, 7, and 28
Description	Laboratory values for chemistry laboratory assessments (e.g., Creatinine and Total Bilirubin) on Days 3, 7, and 28.
Time Frame	Measured on Day 3, Day, 7 and Day 28

Outcome Measure Data

Analysis Population Description

This analysis was based on the Intent to Treat (ITT) population.

Arm/Group Title	Nitazoxanide (NTZ)	Placebo
Arm/Group Description	Participants will receive NTZ for 5 days. Participants younger than 12 years will receive an oral suspension formulation of NTZ; participants 12 years and older will receive NTZ tablets. Nitazoxanide (NTZ): Participants 1 to 3 years old: 5 mL oral suspension (100 mg NTZ) every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL oral suspension (200 mg NTZ) every 12 hours for 5 days. Participants 12 years and older: two 300-mg NTZ tablets orally twice daily for 5 days.	Participants will receive placebo for 5 days. Participants younger than 12 years will receive an oral suspension formulation of placebo; participants 12 years and older will receive placebo tablets. Placebo: Participants 1 to 3 years old: 5 mL placebo oral suspension every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL placebo oral suspension every 12 hours for 5 days. Participants 12 years and older: two placebo tablets orally twice daily for 5 days.
Measure Participants	130	127
Creatinine (mg/dL): Day 3	0.5 (0.3)	0.6 (0.4)
Creatinine (mg/dL): Day 7	1.1 (5.3)	0.6 (0.3)
Creatinine (mg/dL): Day 28	0.6 (1.1)	0.6 (0.4)
Total Bilirubin (mg/dL): Day 3	0.6 (0.4)	0.5 (0.3)
Total Bilirubin (mg/dL): Day 7	1.0 (4.6)	0.5 (0.3)
Total Bilirubin (mg/dL): Day 28	0.6 (0.3)	0.6 (0.3)

18. Secondary Outcome

Title	Chemistry Laboratory Assessments (ALT, AST, LDH) on Days 3, 7, and 28
Description	Chemistry laboratory assessments (e.g., ALT, AST, and LDH) on Days 3, 7, and 28.
Time Frame	Measured on Day 3, Day 7, and Day 28

Outcome Measure Data

Analysis Population Description

This analysis was based on the Intent to Treat (ITT) population.

Arm/Group Title	Nitazoxanide (NTZ)	Placebo
Arm/Group Description	Participants will receive NTZ for 5 days. Participants younger than 12 years will receive an oral suspension formulation of NTZ; participants 12 years and older will receive NTZ tablets. Nitazoxanide (NTZ): Participants 1 to 3 years old: 5 mL oral suspension (100 mg NTZ) every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL oral suspension (200 mg NTZ) every 12 hours for 5 days. Participants 12 years and older: two 300-mg NTZ tablets orally twice daily for 5 days.	Participants will receive placebo for 5 days. Participants younger than 12 years will receive an oral suspension formulation of placebo; participants 12 years and older will receive placebo tablets. Placebo: Participants 1 to 3 years old: 5 mL placebo oral suspension every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL placebo oral suspension every 12 hours for 5 days. Participants 12 years and older: two placebo tablets orally twice daily for 5 days.
Measure Participants	130	127
ALT (SGPT) (U/L): Day 3	32.7 (24.6)	30.9 (27.2)
ALT (SGPT) (U/L): Day 7	33.1 (20.5)	35.1 (28.7)
ALT (SGPT) (U/L): Day 28	26.7 (15.4)	27.4 (16.8)
AST (SGOT) (U/L): Day 3	32.7 (19.4)	36.1 (30.4)
AST (SGOT) (U/L): Day 7	33.2 (20.2)	33.2 (19.0)
AST (SGOT) (U/L): Day 28	33.0 (20.0)	31.8 (18.5)
LDH (U/L): Day 3	248.1 (164.8)	266.8 (180.0)
LDH (U/L): Day 7	250.3 (151.4)	255.2 (150.8)
LDH (U/L): Day 28	241.8 (141.6)	249.7 (151.3)

19. Secondary Outcome

Title	Chemistry Laboratory Assessment (CRP) on Days 3, 7, and 28
Description	Lab Values for chemistry laboratory assessment (e.g., CRP) on Days 3, 7, and 28.
Time Frame	Measured on Day 3, Day, 7 and Day 28

Outcome Measure Data

Analysis Population Description

This analysis was based on the Intent to Treat (ITT) population.

Arm/Group Title	Nitazoxanide (NTZ)	Placebo
Arm/Group Description	Participants will receive NTZ for 5 days. Participants younger than 12 years will receive an oral suspension formulation of NTZ; participants 12 years and older will receive NTZ tablets. Nitazoxanide (NTZ): Participants 1 to 3 years old: 5 mL oral suspension (100 mg NTZ) every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL oral suspension (200 mg NTZ) every 12 hours for 5 days. Participants 12 years and older: two 300-mg NTZ tablets orally twice daily for 5 days.	Participants will receive placebo for 5 days. Participants younger than 12 years will receive an oral suspension formulation of placebo; participants 12 years and older will receive placebo tablets. Placebo: Participants 1 to 3 years old: 5 mL placebo oral suspension every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL placebo oral suspension every 12 hours for 5 days. Participants 12 years and older: two placebo tablets orally twice daily for 5 days.
Measure Participants	130	127
CRP (mg/L): Day 3	2.3 (4.1)	2.2 (3.4)
CRP (mg/L): Day 7	1.2 (3.3)	1.1 (2.4)
CRP (mg/L): Day 28	1.1 (3.7)	0.5 (0.7)

20. Secondary Outcome

Title	Hematologic Laboratory Assessments (Neutrophils, Lymphocytes, Eosinophils, and Hematocrit) on Days 3, 7, and 28
Description	Hematology laboratory assessments (e.g., Neutrophils, Lymphocytes, Eosinophils, and Hematocrit) on Days 3, 7, and 28.
Time Frame	Measured on Day 3, Day, 7 and Day 28

Outcome Measure Data

Analysis Population Description

This analysis was based on the Intent to Treat (ITT) population.

Arm/Group Title	Nitazoxanide (NTZ)	Placebo
Arm/Group Description	Participants will receive NTZ for 5 days. Participants younger than 12 years will receive an oral suspension formulation of NTZ; participants 12 years and older will receive NTZ tablets. Nitazoxanide (NTZ): Participants 1 to 3 years old: 5 mL oral suspension (100 mg NTZ) every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL oral suspension (200 mg NTZ) every 12 hours for 5 days. Participants 12 years and older: two 300-mg NTZ tablets orally twice daily for 5 days.	Participants will receive placebo for 5 days. Participants younger than 12 years will receive an oral suspension formulation of placebo; participants 12 years and older will receive placebo tablets. Placebo: Participants 1 to 3 years old: 5 mL placebo oral suspension every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL placebo oral suspension every 12 hours for 5 days. Participants 12 years and older: two placebo tablets orally twice daily for 5 days.
Measure Participants	130	127
Neutrophils (%): Day 3	59.1 (19.8)	55.9 (19.3)
Neutrophils (%): Day 7	52.4 (21.0)	52.3 (17.0)
Neutrophils (%): Day 28	51.4 (16.6)	49.8 (17.2)
Lymphocytes (%): Day 3	31.6 (17.5)	33.4 (17.0)
Lymphocytes (%): Day 7	36.5 (19.3)	36.7 (16.0)
Lymphocytes (%): Day 28	36.1 (15.2)	37.5 (16.9)
Eosinophils (%): Day 3	1.5 (2.2)	2.3 (5.2)
Eosinophils (%): Day 7	2.3 (1.9)	2.6 (2.7)
Eosinophils (%): Day 28	3.8 (4.3)	3.6 (4.1)
Hematocrit (%): Day 3	41.3 (5.6)	40.6 (6.1)
Hematocrit (%): Day 7	40.7 (5.3)	40.9 (6.1)
Hematocrit (%): Day 28	41.2 (4.6)	41.7 (6.1)

21. Secondary Outcome

Title	Hematologic Laboratory Assessment (Hemoglobin) on Days 3, 7, and 28
Description	Hematology laboratory assessment (e.g., Hemoglobin) on Days 3, 7, and 28.
Time Frame	Measured on Day 3, Day, 7 and Day 28

Outcome Measure Data

Analysis Population Description

This analysis was based on the Intent to Treat (ITT) population.

Arm/Group Title	Nitazoxanide (NTZ)	Placebo
Arm/Group Description	Participants will receive NTZ for 5 days. Participants younger than 12 years will receive an oral suspension formulation of NTZ; participants 12 years and older will receive NTZ tablets. Nitazoxanide (NTZ): Participants 1 to 3 years old: 5 mL oral suspension (100 mg NTZ) every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL oral suspension (200 mg NTZ) every 12 hours for 5 days. Participants 12 years and older: two 300-mg NTZ tablets orally twice daily for 5 days.	Participants will receive placebo for 5 days. Participants younger than 12 years will receive an oral suspension formulation of placebo; participants 12 years and older will receive placebo tablets. Placebo: Participants 1 to 3 years old: 5 mL placebo oral suspension every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL placebo oral suspension every 12 hours for 5 days. Participants 12 years and older: two placebo tablets orally twice daily for 5 days.
Measure Participants	130	127
Hemoglobin (g/dL): Day 3	13.5 (1.8)	13.2 (2.0)
Hemoglobin (g/dL): Day 7	13.5 (1.7)	13.4 (2.1)
Hemoglobin (g/dL): Day 28	13.6 (1.5)	13.6 (2.0)

22. Secondary Outcome

Title	Hematologic Laboratory Assessments (WBC, Platelets) on Days 3, 7, and 28
Description	Lab values for hematology laboratory assessments (e.g., WBC and Platelets) on Days 3, 7, and 28.
Time Frame	Measured on Day 3, Day, 7 and Day 28

Outcome Measure Data

Analysis Population Description

This analysis was based on the Intent to Treat (ITT) population.

Arm/Group Title	Nitazoxanide (NTZ)	Placebo
Arm/Group Description	Participants will receive NTZ for 5 days. Participants younger than 12 years will receive an oral suspension formulation of NTZ; participants 12 years and older will receive NTZ tablets. Nitazoxanide (NTZ): Participants 1 to 3 years old: 5 mL oral suspension (100 mg NTZ) every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL oral suspension (200 mg NTZ) every 12 hours for 5 days. Participants 12 years and older: two 300-mg NTZ tablets orally twice daily for 5 days.	Participants will receive placebo for 5 days. Participants younger than 12 years will receive an oral suspension formulation of placebo; participants 12 years and older will receive placebo tablets. Placebo: Participants 1 to 3 years old: 5 mL placebo oral suspension every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL placebo oral suspension every 12 hours for 5 days. Participants 12 years and older: two placebo tablets orally twice daily for 5 days.
Measure Participants	130	127
WBC (10^3 cells/mcL): Day 3	9.0 (3.9)	8.2 (3.4)
WBC (10^3 cells/mcL): Day 7	9.8 (3.9)	9.1 (3.8)
WBC (10^3 cells/mcL): Day 28	8.1 (3.1)	8.2 (3.3)
Platelets (10^3 cells/mcL): Day 3	301.3 (123.5)	295.8 (113.7)
Platelets (10^3 cells/mcL): Day 7	364.7 (155.9)	393.3 (191.2)
Platelets (10^3 cells/mcL): Day 28	269.0 (85.5)	267.5 (110.9)

Adverse Events

Time Frame	AEs were recorded for each subject starting at completing the Informed Consent process and continuing until the subject completed study, or until resolution of the adverse event as recorded by the clinical site (up to Day 28).
Adverse Event Reporting Description	The definition of AEs and SAEs used to collect AE event information for this study does not differ from the clinicaltrials.gov definitions. The study Investigators evaluated AEs with respect to Seriousness (as per the protocol), Severity (grading), and Causality according to the "DAIDS (Division of AIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events" Version 1.0, December 2004: (Clarification August 2009)
Arm/Group Title	Nitazoxanide (NTZ)		Placebo
Arm/Group Description	Participants will receive NTZ for 5 days. Participants younger than 12 years will receive an oral suspension formulation of NTZ; participants 12 years and older will receive NTZ tablets. Nitazoxanide (NTZ): Participants 1 to 3 years old: 5 mL oral suspension (100 mg NTZ) every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL oral suspension (200 mg NTZ) every 12 hours for 5 days. Participants 12 years and older: two 300-mg NTZ tablets orally twice daily for 5 days.		Participants will receive placebo for 5 days. Participants younger than 12 years will receive an oral suspension formulation of placebo; participants 12 years and older will receive placebo tablets. Placebo: Participants 1 to 3 years old: 5 mL placebo oral suspension every 12 hours for 5 days. Participants 4 to 11 years old: 10 mL placebo oral suspension every 12 hours for 5 days. Participants 12 years and older: two placebo tablets orally twice daily for 5 days.
All Cause Mortality
	Nitazoxanide (NTZ)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/130 (1.5%)		1/127 (0.8%)
Serious Adverse Events
	Nitazoxanide (NTZ)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/130 (4.6%)		3/127 (2.4%)
Blood and lymphatic system disorders
Neutropenia	0/130 (0%)	0	1/127 (0.8%)	1
Infections and infestations
Aspergillosis	1/130 (0.8%)	1	0/127 (0%)	0
Pneumonia	1/130 (0.8%)	1	2/127 (1.6%)	2
Pneumonia Viral	1/130 (0.8%)	1	0/127 (0%)	0
Septic Shock	1/130 (0.8%)	1	1/127 (0.8%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Immune Reconstitution Inflammatory Syndrome Associated Kaposi's Sarcoma	0/130 (0%)	0	1/127 (0.8%)	1
Psychiatric disorders
Delirium	1/130 (0.8%)	1	0/127 (0%)	0
Respiratory, thoracic and mediastinal disorders
Respiratory Failure	2/130 (1.5%)	2	1/127 (0.8%)	1
Other (Not Including Serious) Adverse Events
	Nitazoxanide (NTZ)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/130 (20%)		26/127 (20.5%)
Gastrointestinal disorders
Vomitting	8/130 (6.2%)	9	14/127 (11%)	14
General disorders
Pyrexia	8/130 (6.2%)	8	5/127 (3.9%)	5
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea	10/130 (7.7%)	10	7/127 (5.5%)	7

Limitations/Caveats

There were no significant limitations of the study.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.