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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01610245




Registration number
NCT01610245
Ethics application status
Date submitted
30/05/2012
Date registered
1/06/2012
Date last updated
29/03/2018

Titles & IDs
Public title
Safety and Efficacy Study of Nitazoxanide in the Treatment of Acute Uncomplicated Influenza
Scientific title
A Phase III, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Nitazoxanide and Nitazoxanide Plus Oseltamivir in the Treatment of Acute Uncomplicated Influenza
Secondary ID [1] 0 0
RM08-3002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Influenza 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Nitazoxanide
Treatment: Drugs - Oseltamivir
Treatment: Drugs - Placebo Oral Tablet
Treatment: Drugs - Placebo Oral Capsule

Active Comparator: Nitazoxanide - Two Nitazoxanide 300 mg tablets and one placebo capsule twice daily with food for 5 days

Active Comparator: Oseltamivir - Two placebo tablets and one Oseltamivir 75 mg capsule twice daily with food for 5 days

Active Comparator: Nitazoxanide and Oseltamivir - Two nitazoxanide 300 mg tablets and one Oseltamivir 75 mg capsule twice daily with food for 5 days

Placebo Comparator: Placebo - Two placebo tablets and one placebo capsule with food twice daily for 5 days


Treatment: Drugs: Nitazoxanide


Treatment: Drugs: Oseltamivir


Treatment: Drugs: Placebo Oral Tablet


Treatment: Drugs: Placebo Oral Capsule
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time to resolution of all clinical symptoms of influenza as reported by the subjects
Timepoint [1] 0 0
Up to 28 days
Secondary outcome [1] 0 0
Time to resolution of each individual symptom of influenza
Timepoint [1] 0 0
Up to 28 days

Eligibility
Key inclusion criteria
1. Age 13 to 65 years

2. Presence of clinical signs and/or symptoms consistent with acute illness compatible
with influenza infection (each of the following is required):

1. oral temperature of =100.4 °F or =38 °C (obtained in office or self-measured
within 12 hours prior to screening - if self-measured, subject must also have
taken an antipyretic within 4 hours prior to screening) AND

2. at least one of the following respiratory symptoms (cough, sore throat, nasal
obstruction) that is considered by the patient to be moderate or severe (greater
than mild severity) AND

3. one of the following constitutional symptoms (fatigue, headache, myalgia,
feverishness) that is considered by the patient to be moderate or severe (greater
than mild severity).

3. Confirmation of influenza A or B infection in the local community by one of the
following means:

1. the institution's local laboratory, or

2. the local public health system, or

3. the national public health system, or

4. a laboratory of a recognized national or multinational influenza surveillance
scheme.

4. Onset of illness no more than 48 hours before enrollment in the trial.

Note: 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 subject experienced the presence of at least one respiratory
symptom AND the presence of at least one constitutional symptom.

5. Willing and able to provide written informed consent (including assent by legal
guardian if under 18 years of age) and comply with the requirements of the protocol,
including completion of the patient diary.
Minimum age
13 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Severity of illness requiring or anticipated to require in-hospital care or subject
defined as being at high risk of complications from influenza infection according to
the Infectious Diseases Society of America (IDSA) guidelines for seasonal influenza in
adults and children (Committee of Infectious Diseases (CID) 2009:48) or current
Centers for Disease Control and Prevention (CDC) criteria. Current criteria for
persons 13-65 years of age who are at risk of influenza complications include (list to
be reviewed and updated as required prior to initiation of the study and at least
monthly during the study):

1. Persons with asthma or other chronic pulmonary diseases, such as cystic fibrosis
in children or chronic obstructive pulmonary disease in adults.

2. Persons with hemodynamically significant cardiac disease.

3. Persons who have immunosuppressive disorders or who are receiving
immunosuppressive therapy.

4. HIV-infected persons.

5. Persons with sickle cell anemia or other hemoglobinopathies.

6. Persons with diseases requiring long-term aspirin therapy, such as rheumatoid
arthritis or Kawasaki disease.

7. Persons with chronic renal dysfunction.

8. Persons with liver disorders.

9. Persons with cancer.

10. Persons with chronic metabolic disease, such as diabetes mellitus, inherited
metabolic disorders and mitochondrial disorders.

11. Persons with neuromuscular disorders, seizure disorders or cognitive dysfunction
that may compromise the handling of respiratory secretions.

12. Residents of any age of nursing homes or other long-term care institutions.

13. Persons who are morbidly obese (Body Mass Index =40)

14. American Indians (seemed to be at higher risk of complications last flu season)

15. Alaskan natives (seemed to be at higher risk of complications last flu season)

2. Females of childbearing potential who are either pregnant, breast-feeding or are
sexually active without the use of birth control. Female patients of child-bearing
potential that are sexually active must have a negative baseline pregnancy test and
must agree to continue an acceptable method of birth control for the duration of the
study and for 1 month post-treatment. A double barrier method, oral birth control
pills administered for at least 2 monthly cycles prior to study drug administration,
an intrauterine device (IUD), or medroxyprogesterone acetate administered
intramuscularly for a minimum of one month prior to study drug administration are
acceptable methods of birth control for inclusion into the study. Female subjects are
considered of childbearing potential unless they are postmenopausal (absence of
menstrual bleeding for 1 year - or 6 months if laboratory confirmation of hormonal
status), or have had a hysterectomy, bilateral tubular ligation or bilateral
ovariectomy.

3. Vaccination for seasonal influenza on or after i. August 1, 2012 in the case of
subjects enrolled during the 2012/2013 flu season in the United States, ii. February
1, 2013 in the case of subjects enrolled during the 2013 flu season in Australia or
New Zealand, or iii. August 1, 2013 in the case of subjects enrolled during the
2013/2014 flu season in the United States, Canada, Europe, or other countries in the
Northern Hemisphere, or iv. February 1, 2014 in the case of subjects enrolled during
the 2014 flu season in Australia or New Zealand, or v. August 1, 2014 in the case of
subjects enrolled during the 2014/2015 flu season in the United States, Canada,
Europe, or other countries in the Northern Hemisphere.

4. Receipt of any dose of nitazoxanide, oseltamivir, zanamivir, amantadine, or
rimantadine within 30 days prior to screening.

5. Prior treatment with any investigational drug therapy within 30 days prior to
screening.

6. Subjects with active respiratory allergies or subjects expected to require
anti-allergy medications during the study period for respiratory allergies.

7. Known sensitivity to Nitazoxanide or any of the excipients comprising the Nitazoxanide
tablets.

8. Known sensitivity to Oseltamivir or any of the excipients comprising the Oseltamivir
capsules.

9. Subjects unable to take oral medications.

10. Subject has chronic kidney or liver disease (including Hepatitis A,B or C) or known
impaired hepatic and/or renal function.

11. Presence of any other pre-existing chronic infection that is undergoing or requiring
medical therapy.

12. Presence of any pre-existing illness that, in the opinion of the investigator, would
place the subject at an unreasonably increased risk through participation in this
study.

13. Subjects who, in the judgment of the investigator, will be unlikely to comply with the
requirements of this protocol.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/03/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
16/04/2015
Sample size
Target
Accrual to date
Final
1941
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Influence Study Site - Cardiff
Recruitment hospital [2] 0 0
Influence Study Site - Castle Hill
Recruitment hospital [3] 0 0
Influence Study Site - Darlinghurst
Recruitment hospital [4] 0 0
Influence Study Site - Westmead, Sydney
Recruitment hospital [5] 0 0
Influence Study Site - Chermside
Recruitment hospital [6] 0 0
Influence Study Site - Sherwood
Recruitment hospital [7] 0 0
Influence Study Site - Daw Park
Recruitment hospital [8] 0 0
Influence Study Site - Clayton
Recruitment hospital [9] 0 0
Influence Study Site - Fitzroy North
Recruitment hospital [10] 0 0
Influence Study Site - Prahran
Recruitment hospital [11] 0 0
Influence Study SIte - Nedlands
Recruitment postcode(s) [1] 0 0
2285 - Cardiff
Recruitment postcode(s) [2] 0 0
2154 - Castle Hill
Recruitment postcode(s) [3] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [4] 0 0
2145 - Westmead, Sydney
Recruitment postcode(s) [5] 0 0
4032 - Chermside
Recruitment postcode(s) [6] 0 0
4075 - Sherwood
Recruitment postcode(s) [7] 0 0
5041 - Daw Park
Recruitment postcode(s) [8] 0 0
3168 - Clayton
Recruitment postcode(s) [9] 0 0
3068 - Fitzroy North
Recruitment postcode(s) [10] 0 0
3181 - Prahran
Recruitment postcode(s) [11] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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United States of America
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Arizona
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United States of America
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Arkansas
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United States of America
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California
Country [5] 0 0
United States of America
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Colorado
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
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Idaho
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United States of America
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Illinois
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Indiana
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Kansas
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United States of America
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Kentucky
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United States of America
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Louisiana
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Massachusetts
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United States of America
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Michigan
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Missouri
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United States of America
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Nebraska
Country [18] 0 0
United States of America
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Nevada
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United States of America
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New Jersey
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United States of America
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New Mexico
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United States of America
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New York
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United States of America
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North Carolina
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United States of America
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Ohio
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United States of America
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Oklahoma
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Oregon
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Pennsylvania
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Rhode Island
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South Carolina
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United States of America
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South Dakota
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United States of America
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Tennessee
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United States of America
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Texas
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United States of America
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Utah
Country [33] 0 0
United States of America
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Virginia
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United States of America
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Washington
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United States of America
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Wisconsin
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Belgium
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Antwerpen
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Canada
State/province [37] 0 0
British Columbia
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Canada
State/province [38] 0 0
Ontario
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Canada
State/province [39] 0 0
Quebec
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New Zealand
State/province [40] 0 0
Auckland
Country [41] 0 0
New Zealand
State/province [41] 0 0
Bay Of Plenty
Country [42] 0 0
New Zealand
State/province [42] 0 0
Christchurch

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Romark Laboratories L.C.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study is a global multicenter randomized factorial double-blind, placebo-controlled
trial designed to evaluate (i) efficacy and safety of nitazoxanide 600 mg administered orally
twice daily for five days compared to a placebo in the treatment of acute uncomplicated
influenza and (ii) efficacy and safety of combination therapy with nitazoxanide 600 mg plus
Oseltamivir 75 mg co-administered orally twice daily for five days compared to nitazoxanide
monotherapy (600 mg b.i.d. for 5 days) and Oseltamivir monotherapy (75 mg b.i.d. for 5 days)
in the treatment of acute uncomplicated influenza.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01610245
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jean-Francois Rossignol, M.D., Ph.D.
Address 0 0
Romark Laboratories L.C.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01610245