Study of Nitazoxanide in Adults With Acute Uncomplicated Influenza

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of Nitazoxanide in Adults With Acute Uncomplicated Influenza

Conditions
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Influenza

Intervention / Treatment
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* Drug: Nitazoxanide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Nitazoxanide<br> | Drug: Nitazoxanide<br>* Tablet, 500 mg with food twice daily for 5 days<br>* Other names: Alinia, NTZ;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Tablet, twice daily with food for 5 days<br>* Other names: Sugar pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Resolution of All Clinical Symptoms of Influenza (Subjects With Confirmed Influenza Infection) |  | Up to 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Resolution of All Clinical Symptoms of Influenza (Subjects Infected With Any Respiratory Virus) |  | Up to 28 days | 
| Time to Resolution of All Clinical Symptoms of Influenza (All Treated Subjects) |  | Up to 28 days | 
| Time to Return to Normal Daily Activity (Subjects With Confirmed Influenza) |  | Up to 28 days | 
| Overall Severity of Disease Score | 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. | Up to 14 days | 
| Time Lost From Work (Subjects With Confirmed Influenza) |  | Up to 28 days | 
| Complications of Influenza Including Secondary Illnesses, Antibiotic Use and Hospitalizations (Subjects With Confirmed Influenza) |  | Up to 28 days | 
| Time to Cessation of Viral Shedding (Subjects With Confirmed Influenza) |  | 28 days | 
| Change in Influenza Virus Titer Assessed by Quantitative RT-PCR (Subjects With Confirmed Influenza) |  | 4 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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influenza, influenza like illness