Efficacy and Safety of Nitazoxanide in the Treatment of Colds Due to Enterovirus/Rhinovirus Infection

Rhinovirus Clinical Trial

Official title:

A Phase III, Randomized, Double-Blind, Placebo Controlled Trial to Evaluate the Efficacy and Safety of Nitazoxanide in the Treatment of Colds Due to Enterovirus/Rhinovirus Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03605862
• Other study ID #: RM08-3005
• Status: Completed
• Phase: Phase 3
• Start date: September 11, 2018
• Est. completion date: February 4, 2019

Study information

• Verified date: April 2022
• Source: Romark Laboratories L.C.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Trial to evaluate efficacy and safety of nitazoxanide in the treatment of colds due to Enterovirus/Rhinovirus infection

Description:

Multicenter, randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety of nitazoxanide in the treatment of colds due to Enterovirus/Rhinovirus infection

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1756
• Est. completion date: February 4, 2019
• Est. primary completion date: February 4, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

1. Male and female subjects at least 12 years of age

2. Presence of clinical signs and/or symptoms consistent with an acute illness compatible

with EV/RV infection (each of the following is required):

1. Presence of moderate or severe rhinorrhea defined as "attempting to relieve nasal symptoms by blowing, wiping, or sniffling at least twice per hour for any one hour within 12 hours preceding study entry," AND

2. Presence of cough, sore throat or nasal obstruction.

3. Negative rapid influenza diagnostic test (required only if the subject has an oral temperature >100°F in the clinic or if the latest CDC weekly influenza report shows influenza prevalence "Regional" or higher for the institution's state). A result from a rapid influenza diagnostic test performed on the same day that informed consent is obtained will be sufficient to meet this criterion if documentation of test results is available as part of medical history.

4. Onset of illness no more than 40 hours before enrollment in the trial. Onset of illness is defined as the first time at which the subject experienced rhinorrhea, cough, sore throat or nasal obstruction.

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 subject diary

Exclusion Criteria:

1. Persons requiring or anticipated to require in-hospital care

2. Cystic fibrosis

3. Cardiac arrhythmia

4. Immunologic disorders or receiving immunosuppressive therapy (e.g., for organ or bone marrow transplants, immunomodulatory therapies for certain autoimmune diseases)

5. Untreated HIV infection or treated HIV infection with a CD4 count below 350 cells/mm3 in the last 6 months

6. Persons with sickle cell anemia or other hemoglobinopathies

7. Poorly controlled insulin-dependent diabetes mellitus (HbA1C >8.0%)

8. Concurrent infection at the screening examination that requires systemic antimicrobial therapy

9. Females of childbearing potential who are either pregnant or sexually active without the use of birth control. Female subjects 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 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 oophorectomy.

10. Females who are breastfeeding

11. Receipt of any dose of NTZ within 30 days prior to screening

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

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

14. Known sensitivity to NTZ or any of the excipients comprising the NTZ tablets

15. Subjects unable to take oral medications

16. Subjects who, in the judgment of the Investigator, will be unlikely to comply with the requirements of this protocol including completion of the subject diary

Related Conditions & MeSH terms

• Enterovirus
• Enterovirus Infections
• Rhinovirus

Intervention

Drug:
• Nitazoxanide
Nitazoxanide 600 mg administered orally twice daily for five days
• Placebo
Placebo administered orally twice daily for five days

Locations

Country	Name	City	State
Puerto Rico	Vanguard Study Site	Ponce
Puerto Rico	Vanguard Study Site	San Juan
United States	Vanguard Study Site	Anaheim	California
United States	Vanguard Study Site	Austin	Texas
United States	Vanguard Study Site	Baltimore	Maryland
United States	Vanguard Study Site	Bellevue	Nebraska
United States	Vanguard Study Site	Birmingham	Alabama
United States	Vanguard Study Site	Birmingham	Alabama
United States	Vanguard Study Site	Blackfoot	Idaho
United States	Vanguard Study Site	Bountiful	Utah
United States	Vanguard Study Site	Brooklyn	New York
United States	Vanguard Study Site	Carrollton	Texas
United States	Vanguard Study Site	Cincinnati	Ohio
United States	Vanguard Study Site	Cleveland	Ohio
United States	Vanguard Study Site	Columbus	Ohio
United States	Vanguard Study Site	Dayton	Ohio
United States	Vanguard Study Site	East Providence	Rhode Island
United States	Vanguard Study Site	Evanston	Illinois
United States	Vanguard Study Site	Hot Springs	Arkansas
United States	Vanguard Study Site	Houston	Texas
United States	Vanguard Study Site	Jackson	Tennessee
United States	Vanguard Study Site	Las Vegas	Nevada
United States	Vanguard Study Site	Louisville	Kentucky
United States	Vanguard Study Site	McAllen	Texas
United States	Vanguard Study Site	Medford	Oregon
United States	Vanguard Study Site	Meridian	Idaho
United States	Vanguard Study Site	Miami	Florida
United States	Vanguard Study Site	Miami	Florida
United States	Vanguard Study Site	Miami	Florida
United States	Vanguard Study Site	Milan	Tennessee
United States	Vanguard Study Site	Missoula	Montana
United States	Vanguard Study Site	Nampa	Idaho
United States	Vanguard Study Site	New Orleans	Louisiana
United States	Vanguard Study Site	New Orleans	Louisiana
United States	Vanguard Study Site	Orlando	Florida
United States	Vanguard Study Site	Pelham	Alabama
United States	Vanguard Study Site	Plano	Texas
United States	Vanguard Study Site	Raleigh	North Carolina
United States	Vanguard Study Site	Saint George	Utah
United States	Vanguard Study Site	Saint Louis	Missouri
United States	Vanguard Study Site	Stockbridge	Georgia
United States	Vanguard Study Site	Tampa	Florida
United States	Vanguard Study Site	Valparaiso	Indiana
United States	Vanguard Study Site	Westminster	California
United States	Vanguard Study Site	Wilmington	California

Sponsors (1)

Lead Sponsor	Collaborator
Romark Laboratories L.C.

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Time to Return to Usual Health	Subjects completed the FLU-PRO questionnaire including global assessment questions daily in the evening. The time from first dose to ability to return to usual health is the time in hours from the first dose of study medication to the first time when the subject answered "Have you returned to your usual health?" with "yes" for two consecutive daily diary periods without the use of symptom relief medication.	21 days
Other	Proportion Positive for EV/RV by RT-PCR at Days 2, 3 and 7	Proportion of subjects with nasopharyngeal swab collected testing positive for Enterovirus/Rhinovirus (EV/RV) infection by RT-PCR at each time point.	Days 2, 3, and 7
Other	Analysis of Change From Baseline to Days 2, 3 and 7 in EV/RV Virus Titer	Changes from baseline to day 2, baseline to day 3, and baseline to day 7 in EV/RV virus titer measured by quantitative RT-PCR. Samples negative for EV/RV were assigned the value of the limit of detection for the RT-PCR assay.	Days 2, 3, and 7
Other	Response Misclassification Rate Compared to Usual Health	The proportion of patient diaries misclassified by the response definition used for the primary efficacy analysis compared to patient reported usual health. A diary was considered "misclassified" if the response definition predicted "responded" and the patient reported not being at usual health or if the response definition predicted "not responded" and the patient reported being at usual health.	21 days
Primary	Time From First Dose to Symptom Response Over 21 Days of Follow up Based Upon the FLU-PRO Instrument (Novel Endpoint)	Subjects used the FLU-PRO questionnaire once daily in the evening to score the severity of 32 FLU-PRO symptoms. Symptom response was deemed achieved when the rating for each of the 32 FLU-PRO symptoms was = its assigned threshold for 2 consecutive daily diary periods without use of symptom relief medication. The symptom response thresholds were developed by applying an algorithm to blinded symptoms data to select the set of 32 symptom thresholds most closely associated with patient-reported usual health.	Up to 21 days
Secondary	Time From First Dose to Ability to Perform All Normal Activities	Subjects completed a diary including rating ability to perform normal activities on a scale from 0 (able to perform no normal activities) to 10 (able to perform all normal activities) daily in the evening. The time from first dose to ability to perform all normal activities is the time in hours between the first dose of study medication and that time when the subject first reported a score of "10" (able to perform all normal activities) for two consecutive daily diary periods without use of symptom relief medication.	Up to 21 days
Secondary	Proportions Experiencing Complications of EV/RV Infection	Complications of colds due to EV/RV infection include pneumonia, otitis media, bronchitis, sinusitis, exacerbations of asthma or COPD, worsening of pre-existing health conditions, secondary infections requiring systemic antibiotic use, hospitalization due to cold or complications of the cold, and death due to cold or complications of the cold. Proportions experiencing complications of EV/RV infection were compared across treatment groups.	28 days