Study of Nitazoxanide in Adults With Acute Uncomplicated Influenza

• Sponsor: Romark Laboratories L.C. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01056380
• Collaborator: (none)
• Enrollment: 79
• Location: 1
• Arms: 2
• Duration (Months): 11
• Patients Per Site Per Month: 7.2

Study Details

Study Description

Brief Summary

This is a randomized clinical trial designed to evaluate oral nitazoxanide compared to a placebo in the treatment of acute uncomplicated influenza in adults. We hypothesize that treatment with nitazoxanide will reduce the duration of symptoms in patients with confirmed influenza infection. Secondarily, we hypothesize that treatment with nitazoxanide will reduce the complications of influenza, severity of symptoms, time lost from work, time to return to normal daily activities, and viral shedding.

Condition or Disease	Intervention/Treatment	Phase
Influenza	Drug: Nitazoxanide; Drug: Placebo	Phase 2

Detailed Description

The study is conducted at approximately 25 sites in the United States. Subjects selected based on symptoms will be randomized to receive oral nitazoxanide or placebo twice daily for 5 days. Subjects will be monitored by daily by telephone or home visit to monitor symptoms and complications of influenza for safety and will be referred for medical care as required. Subjects will complete a diary twice daily to record the presence and severity of symptoms, ability to perform normal daily activities and time lost from work. Complications of influenza (including sinusitis, otitis, bronchitis, pneumonia, central nervous system disease) and other adverse events will be reported. Nasopharyngeal swabs will be collected at Baseline (Day 0) and Day 7 for all patients and on Days 1 through 4 for a subset of patients to test for influenza A (including novel H1N1), influenza B and 17 other respiratory viruses by RT-PCR and culture and to evaluate quantitative viral shedding. The primary analysis will be for patients with confirmed influenza, and secondary analyses will be conducted for subjects with any respiratory virus and for all treated subjects.

Study Design

• Study Type: Interventional
• Actual Enrollment: 79 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of Nitazoxanide in Adults With Acute Uncomplicated Influenza
• Study Start Date: Jan 1, 2010
• Actual Primary Completion Date: Dec 1, 2010
• Actual Study Completion Date: Dec 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Nitazoxanide	Drug: Nitazoxanide; Tablet, 500 mg with food twice daily for 5 days; Other Names: Alinia, NTZ
Placebo Comparator: Placebo	Drug: Placebo; Tablet, twice daily with food for 5 days; Other Names: Sugar pill

Outcome Measures

Primary Outcome Measures

1. Time to Resolution of All Clinical Symptoms of Influenza (Subjects With Confirmed Influenza Infection) [Up to 28 days]

Secondary Outcome Measures

1. Time to Resolution of All Clinical Symptoms of Influenza (Subjects Infected With Any Respiratory Virus) [Up to 28 days]

2. Time to Resolution of All Clinical Symptoms of Influenza (All Treated Subjects) [Up to 28 days]

3. Time to Return to Normal Daily Activity (Subjects With Confirmed Influenza) [Up to 28 days]

4. Overall Severity of Disease Score [Up to 14 days]

   Subjects recorded a severity score for 10 flu symptoms on a 0-3 scale BID for 7-14 days.The severity score for each symptom was multiplied by the number of hours scored at that severity for the entire time the subject maintained a diary (a sneezing score of 1 for 12 hours and 0 for 10 hours =1*12 + 0*10=12). This is symptom severity score*hours.Symptom severity score*hours for each of the symptoms were added for an overall symptom severity score*hours (if symptom severity score*hours for 10 symptoms were 12, 10, 9, 8, 7, 10, 10, 10, 5, 5, overall symptom severity score*hours=86).Overall symptom severity score*hours were divided by the number of hours that the subject kept a diary for a standardized continuous measure of severity of the course of illness (if overall symptom severity score*hours=86 and the subject maintained a diary for 100 hours Overall Severity of Disease Score=0.86). Overall Severity of Disease Score can range 0-30 with higher scores indicating more severe symptoms.

5. Time Lost From Work (Subjects With Confirmed Influenza) [Up to 28 days]

6. Complications of Influenza Including Secondary Illnesses, Antibiotic Use and Hospitalizations (Subjects With Confirmed Influenza) [Up to 28 days]

7. Time to Cessation of Viral Shedding (Subjects With Confirmed Influenza) [28 days]

8. Change in Influenza Virus Titer Assessed by Quantitative RT-PCR (Subjects With Confirmed Influenza) [4 days]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age 18 to 65 years

• Fever, respiratory symptoms and constitutional symptoms compatible with influenza infection

• Influenza A or B infection in the local community

• Onset of illness no more than 48 hours before presentation

• Willing and able to provide comply with protocol requirements

Exclusion Criteria:

• Severity of illness requiring or anticipated to require in-hospital care

• High risk of complications from influenza per IDSA (Infectious Diseases Society of America) guidelines or current CDC (Centers for Disease Control) criteria

• Females pregnant, breast-feeding or sexually active without birth control

• Vaccination for seasonal influenza or H1N1 on or after August 1, 2009

• Treatment with antiviral medication for influenza within 1 month prior to screening

• Treatment with nitazoxanide or any investigational drug within 1 month prior to screening

• Known sensitivity to nitazoxanide or any excipients

• Unable to take oral medications

• Chronic kidney or liver disease or known impaired hepatic and/or renal function

• Other pre-existing chronic infection undergoing or requiring medical therapy

• Pre-existing illness placing subject at unreasonably increased risk by participation in study

• Unlikely to comply with the requirements of this protocol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Health Sciences Research Center at Asthma and Allergy Associates, P.C.	Elmira	New York	United States	14901

Sponsors and Collaborators

• Romark Laboratories L.C.

Investigators

• Study Chair: Jean-François Rossignol, MD, PhD, The Romark Institute for Medical Research

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Romark Laboratories L.C.
• ClinicalTrials.gov Identifier: NCT01056380
• Other Study ID Numbers: RM01-2027
• First Posted: Jan 26, 2010
• Last Update Posted: Apr 5, 2018
• Last Verified: Apr 1, 2018

• Keywords provided by Romark Laboratories L.C.: influenza; influenza like illness
• Additional relevant MeSH terms: Influenza, Human; Nitazoxanide

Study Results

Participant Flow

Recruitment Details	Patients were enrolled at 11 primary care health centers throughout the United States in the last months of the 2009/2010 flu season

Arm/Group Title	Nitazoxanide	Placebo
Arm/Group Description	Nitazoxanide : Tablet, 500 mg with food twice daily for 5 days	Placebo : Tablet, twice daily with food for 5 days
Period Title: Overall Study
STARTED	37	42
COMPLETED	35	39
NOT COMPLETED	2	3

Baseline Characteristics

Arm/Group Title	Nitazoxanide	Placebo	Total
Arm/Group Description	Nitazoxanide : Tablet, 500 mg with food twice daily for 5 days	Placebo : Tablet, twice daily with food for 5 days	Total of all reporting groups
Overall Participants	37	42	79
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	37 100%	42 100%	79 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.6 (14.4)	37.9 (13.3)	38.2 (13.8)
Sex: Female, Male (Count of Participants)
Female	21 56.8%	26 61.9%	47 59.5%
Male	16 43.2%	16 38.1%	32 40.5%
Region of Enrollment (participants) [Number]
United States	37 100%	42 100%	79 100%

Outcome Measures

1. Primary Outcome

Title	Time to Resolution of All Clinical Symptoms of Influenza (Subjects With Confirmed Influenza Infection)
Time Frame	Up to 28 days

Outcome Measure Data

Analysis Population Description

All subjects with laboratory confirmed influenza who took at least one dose of study medication.

Arm/Group Title	Nitazoxanide	Placebo
Arm/Group Description	Nitazoxanide : Tablet, 500 mg with food twice daily for 5 days	Placebo : Tablet, twice daily with food for 5 days
Measure Participants	3	3
Median (Inter-Quartile Range) [hours]	55.0	91.5

2. Secondary Outcome

Title	Time to Resolution of All Clinical Symptoms of Influenza (Subjects Infected With Any Respiratory Virus)
Time Frame	Up to 28 days

Outcome Measure Data

Analysis Population Description

All subjects with any laboratory confirmed viral infection who took at least one dose of study medication.

Arm/Group Title	Nitazoxanide	Placebo
Arm/Group Description	Nitazoxanide: Tablet, 500 mg with food twice daily for 5 days	Placebo: Tablet, twice daily with food for 5 days
Measure Participants	20	22
Median (Inter-Quartile Range) [hours]	118.0	88.8

3. Secondary Outcome

Title	Time to Resolution of All Clinical Symptoms of Influenza (All Treated Subjects)
Time Frame	Up to 28 days

Outcome Measure Data

Analysis Population Description

All subjects who received at least one dose of study medication.

Arm/Group Title	Nitazoxanide	Placebo
Arm/Group Description	Nitazoxanide: Tablet, 500 mg with food twice daily for 5 days	Placebo: Tablet, twice daily with food for 5 days
Measure Participants	37	40
Median (Inter-Quartile Range) [hours]	119.8	102.6

4. Secondary Outcome

Title	Time to Return to Normal Daily Activity (Subjects With Confirmed Influenza)
Time Frame	Up to 28 days

Outcome Measure Data

Analysis Population Description

All subjects with laboratory confirmed influenza who received at least one dose of study medication.

Arm/Group Title	Nitazoxanide	Placebo
Arm/Group Description	Nitazoxanide: Tablet, 500 mg with food twice daily for 5 days	Placebo: Tablet, twice daily with food for 5 days
Measure Participants	3	3
Median (Inter-Quartile Range) [hours]	48.5	57.5

5. Secondary Outcome

Title	Overall Severity of Disease Score
Description	Subjects recorded a severity score for 10 flu symptoms on a 0-3 scale BID for 7-14 days.The severity score for each symptom was multiplied by the number of hours scored at that severity for the entire time the subject maintained a diary (a sneezing score of 1 for 12 hours and 0 for 10 hours =1*12 + 0*10=12). This is symptom severity score*hours.Symptom severity score*hours for each of the symptoms were added for an overall symptom severity score*hours (if symptom severity score*hours for 10 symptoms were 12, 10, 9, 8, 7, 10, 10, 10, 5, 5, overall symptom severity score*hours=86).Overall symptom severity score*hours were divided by the number of hours that the subject kept a diary for a standardized continuous measure of severity of the course of illness (if overall symptom severity score*hours=86 and the subject maintained a diary for 100 hours Overall Severity of Disease Score=0.86). Overall Severity of Disease Score can range 0-30 with higher scores indicating more severe symptoms.
Time Frame	Up to 14 days

Outcome Measure Data

Analysis Population Description

All subjects with laboratory confirmed influenza who received at least one dose of study medication.

Arm/Group Title	Nitazoxanide	Placebo
Arm/Group Description	Nitazoxanide: Tablet, 500 mg with food twice daily for 5 days	Placebo: Tablet, twice daily with food for 5 days
Measure Participants	3	3
Mean (Standard Deviation) [overall severity score]	5.4 (3.3)	6.2 (3.6)

6. Secondary Outcome

Title	Time Lost From Work (Subjects With Confirmed Influenza)
Time Frame	Up to 28 days

Outcome Measure Data

Analysis Population Description

All subjects with laboratory confirmed influenza who received at least one dose of study medication.

Arm/Group Title	Nitazoxanide	Placebo
Arm/Group Description	Nitazoxanide: Tablet, 500 mg with food twice daily for 5 days	Placebo: Tablet, twice daily with food for 5 days
Measure Participants	3	3
Least Squares Mean (95% Confidence Interval) [hours]	3.64	4.36

7. Secondary Outcome

Title	Complications of Influenza Including Secondary Illnesses, Antibiotic Use and Hospitalizations (Subjects With Confirmed Influenza)
Time Frame	Up to 28 days

Outcome Measure Data

Analysis Population Description

All subjects with laboratory confirmed influenza who received at least one dose of study medication.

Arm/Group Title	Nitazoxanide	Placebo
Arm/Group Description	Nitazoxanide: Tablet, 500 mg with food twice daily for 5 days	Placebo: Tablet, twice daily with food for 5 days
Measure Participants	3	3
Count of Participants [Participants]	1 2.7%	1 2.4%

8. Secondary Outcome

Title	Time to Cessation of Viral Shedding (Subjects With Confirmed Influenza)
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

All subjects with laboratory confirmed influenza enrolled in the intensive virologic follow up substudy who received at least one dose of study medication.

Arm/Group Title	Nitazoxanide	Placebo
Arm/Group Description	Nitazoxanide: Tablet, 500 mg with food twice daily for 5 days	Placebo: Tablet, twice daily with food for 5 days
Measure Participants	1	2
Median (Inter-Quartile Range) [hours]	95.5	83.3

9. Secondary Outcome

Title	Change in Influenza Virus Titer Assessed by Quantitative RT-PCR (Subjects With Confirmed Influenza)
Time Frame	4 days

Outcome Measure Data

Analysis Population Description

All subjects with laboratory confirmed influenza enrolled in the intensive virologic follow up substudy who received at least one dose of study medication.

Arm/Group Title	Nitazoxanide	Placebo
Arm/Group Description	Nitazoxanide: Tablet, 500 mg with food twice daily for 5 days	Placebo: Tablet, twice daily with food for 5 days
Measure Participants	1	2
Baseline	0 (0)	0 (0)
Day 2	0 (0)	-175183057 (373069697)
Day 3	0 (0)	-176973304 (374681622)
Day 4	0 (0)	-176946354 (375523235)

Adverse Events

Arm/Group Title	Nitazoxanide		Placebo
Arm/Group Description	Nitazoxanide : Tablet, 500 mg with food twice daily for 5 days		Placebo : Tablet, twice daily with food for 5 days
All Cause Mortality
	Nitazoxanide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Nitazoxanide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/37 (0%)		0/42 (0%)
Other (Not Including Serious) Adverse Events
	Nitazoxanide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/37 (24.3%)		6/42 (14.3%)
Ear and labyrinth disorders
Infections and infestations	2/37 (5.4%)	2	2/42 (4.8%)	3
Gastrointestinal disorders
Gastrointestinal disorders	2/37 (5.4%)	3	4/42 (9.5%)	5
General disorders
General disorders and administration site conditions	1/37 (2.7%)	1	1/42 (2.4%)	1
Musculoskeletal and connective tissue disorders
Muscoloskeletal and connective tissue disorders	1/37 (2.7%)	1	0/42 (0%)	0
Nervous system disorders
Nervous system disorders	1/37 (2.7%)	1	2/42 (4.8%)	2
Renal and urinary disorders
Renal and urinary disorders	3/37 (8.1%)	3	0/42 (0%)	0
Reproductive system and breast disorders
Reproductive system and breast disorders	1/37 (2.7%)	1	0/42 (0%)	0
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders	3/37 (8.1%)	3	2/42 (4.8%)	2

Limitations/Caveats

Early termination leading to small numbers of subjects analyzed.

More Information

Certain Agreements

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

Presentation and/or publication is encouraged provided the Sponsor is notified in advance and given the opportunity to review the manuscript or abstract 30 days prior to its submission for presentation at a scientific meeting or for publication in a scientific journal. The investigators will have complete autonomy regarding the content and wording including the decision of whether or not to publish.