Nitazoxanide Versus Placebo for the Treatment of Hospitalized Subjects With Severe Acute Respiratory Illness
Condition: Severe Acute Respiratory Illness
Intervention: Nitazoxanide; Placebo
Intervention description: 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 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.
Intervention MeSH terms: Nitazoxanide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 260.0
Sex: All
Minimum age: 12 Months
Healthy volunteers: No

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.
    

Eligibility criteria:

        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)