Clinical trial NCT01227421: Safety and Efficacy Study of Nitazoxanide in the Treatment of Acute Uncomplicated Influenza
Official title: A Randomized, Double-Blind, Placebo Controlled Study of Nitazoxanide in Adults and Adolescents With Acute Uncomplicated Influenza
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Influenza
Keywords: influenza
Lead sponsor: Romark Laboratories L.C.
Sponsor class: INDUSTRY
First posted: 2010-10-25
Enrollment: 624
Sex: ALL
Minimum age (years): 12
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized clinical trial designed to evaluate the safety/efficacy of two dosing regimens of oral nitazoxanide compared to placebo in the treatment of acute uncomplicated influenza in adults and adolescents. The investigators hypothesize that treatment with Nitazoxanide will reduce the duration of symptoms in patients with confirmed influenza infection. Secondarily, the investigators 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.

Detailed description: A Randomized, Double-Blind, Placebo Controlled Study of Nitazoxanide in Adults and Adolescents with Acute Uncomplicated Influenza. The primary objectives of this study are to demonstrate the efficacy of nitazoxanide administered 300 mg two times per day for 5 days or 600 mg two times per day for 5 days in reducing the time to resolution of all clinical symptoms of influenza.

The study will also evaluate pharmacokinetics of nitazoxanide in a subset of 24 patients and the safety of the nitazoxanide regimen compared to a placebo via analysis of adverse events and laboratory safety tests.

Blood samples will be collected for all patients at baseline, day 7 and day 28, and for a subset of 24 patients aged 18-65 years (pharmacokinetics subset) on day 2. Urine samples will be collected at baseline and day 7. Nasal swabs will be collected at baseline and day 7 for all patients and on days 2, 3, 4 and 5 for a subset of patients (approximately 20% of patients).

Eligibility criteria: INCLUSION CRITERIA

* age 12 to 65 years
* Presence of clinical signs, respiratory symptoms and constitutional symptoms compatible with influenza infection:

  1. fever,
  2. at least one of the following respiratory symptoms: cough, sore throat, nasal discharge, nasal congestion, sneezing.
  3. At least one of the following constitutional symptoms: headache, myalgia, seats, chills, fatigue of any severity (mild, moderate, severe)
* Confirmation of Influenza A or B infection in the local community
* Onset of illness no more than 48 hours before presentation. Time of onset of illness is defined as either the earlier of (1) the time when the temperature was first measured as elevated, or (2) the time when the patient experienced the presence of at least one respiratory symptom AND the presence of at least one constitutional symptom.
* willing and able to comply with protocol requirements and provide informed consent

EXCLUSION CRITERIA:

* severity of illness requiring or anticipated to require in-hospital care
* High risk of complications from influenza as follows:

  1. persons with asthma or other chronic pulmonary diseases
  2. persons with hemodynamically significant cardiac disease
  3. persons who have immunosuppressive disorders or receiving immunosuppressive therapy
  4. persons infected with Human Immunodeficiency Virus (HIV)
  5. persons with sickle cell anemia or other hemoglobinopathies
  6. persons with diseases requiring long-term aspirin therapy
  7. persons with chronic renal dysfunction
  8. persons with liver disorders
  9. Persons with cancer
  10. Persons with chronic metabolic disease such as diabetes and inherited mitochondrial disorders
  11. Persons with neuromuscular disorders, seizure disorders, or cognitive dysfunction
  12. Residents of any age of nursing homes or long-term institutions.
* Females of child bearing age who are pregnant, breastfeeding or sexually active without birth control
* vaccination for influenza or H1N1 (Swine Flu) on or after August 1, 2010
* treatment with antiviral medication such as oseltamivir, zanamivir, amantadine, or rimantadine within 30 days of screening.
* Prior treatment with nitazoxanide within 30 days prior to screening.
* subjects with active respiratory allergies or expected to require anti-allergy medications during the study period.
* known sensitivity to nitazoxanide
* subjects unable to take oral medication
* subjects with chronic kidney or liver disease
* Presence of any other pre-existing chronic infection that is undergoing or requiring medical therapy

Primary outcomes:
measure: Time to Resolution of All Clinical Symptoms of Influenza as Reported by the Subjects
timeFrame: Up to 28 days
Secondary outcomes:
measure: Time to Resolution of Each Individual Symptom of Influenza as Reported by the Subjects
timeFrame: at least 28 days
measure: Mean Change (Standard Deviation)in 50% Tissue Culture Infective Dose (TCID50) Viral Titer From Baseline
timeFrame: 7 days
measure: Mean Change in RT-PCR (Reverse Transcription Polymerase Chain Reaction) Viral Titer From Baseline
timeFrame: 7 days
measure: Time to Cessation of Viral Shedding Measure by 50% Tissue Culture Infective Dose (TCID50)
timeFrame: 28 days
measure: Time to Return to Normal Daily Activities
timeFrame: 28 days
measure: Symptom Severity Score Hours
timeFrame: 28 days
measure: Time Loss From Work
timeFrame: 28 days
measure: Complications of Influenza
timeFrame: 28 days
measure: Influenza Antibody Response Titer Change: Influenza A 2009 H1N1
timeFrame: 28 days
measure: Influenza Antibody Response: Influenza A H3N2
timeFrame: 28 days
measure: Influenza Antibody Response: Influenza B
timeFrame: 28 days
measure: Influenza Antibody Response: Seroprotection and Seroconversion for Patients With Influenza A 2009 H1N1
timeFrame: 28 days
measure: Influenza Antibody Response: Seroprotection and Seroconversion for Patients With Influenza A H3N2
timeFrame: 28 days
measure: Influenza Antibody Response: Seroprotection and Seroconversion for Influenza B
timeFrame: 28 days
Other outcomes:
Locations:
city: Elmira
country: United States
facility: Health Sciences Research Center
state: New York
Study officials:
affiliation: Romark Laboratories L.C.
name: Jean-Francois Rossignol, M.D., Ph.D.
role: STUDY_DIRECTOR
References:
citation: Haffizulla J, Hartman A, Hoppers M, Resnick H, Samudrala S, Ginocchio C, Bardin M, Rossignol JF; US Nitazoxanide Influenza Clinical Study Group. Effect of nitazoxanide in adults and adolescents with acute uncomplicated influenza: a double-blind, randomised, placebo-controlled, phase 2b/3 trial. Lancet Infect Dis. 2014 Jul;14(7):609-18. doi: 10.1016/S1473-3099(14)70717-0. Epub 2014 May 19.