Study of Nitazoxanide in Adults With Acute Uncomplicated Influenza

Phase 2

Terminated

Conditions: Influenza

Interventions: Drug: Placebo
Drug: Nitazoxanide

Registration Number: NCT01056380

Lead Sponsor: Romark Laboratories L.C.

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.

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 79

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
Nitazoxanide	Nitazoxanide	-

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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	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.
Time Lost From Work (Subjects With Confirmed Influenza)	Up to 28 days
Time to Cessation of Viral Shedding (Subjects With Confirmed Influenza)	28 days
Complications of Influenza Including Secondary Illnesses, Antibiotic Use and Hospitalizations (Subjects With Confirmed Influenza)	Up to 28 days
Change in Influenza Virus Titer Assessed by Quantitative RT-PCR (Subjects With Confirmed Influenza)	4 days