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

Phase 3

Completed

Conditions: Rhinovirus
Enterovirus

Interventions: Drug: Nitazoxanide
Drug: Placebo

Registration Number: NCT03605862

Lead Sponsor: Romark Laboratories L.C.

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

Detailed 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 & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1756

Inclusion Criteria

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

Persons requiring or anticipated to require in-hospital care
Cystic fibrosis
Cardiac arrhythmia
Immunologic disorders or receiving immunosuppressive therapy (e.g., for organ or bone marrow transplants, immunomodulatory therapies for certain autoimmune diseases)
Untreated HIV infection or treated HIV infection with a CD4 count below 350 cells/mm3 in the last 6 months
Persons with sickle cell anemia or other hemoglobinopathies
Poorly controlled insulin-dependent diabetes mellitus (HbA1C >8.0%)
Concurrent infection at the screening examination that requires systemic antimicrobial therapy
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.
Females who are breastfeeding
Receipt of any dose of NTZ within 30 days prior to screening
Prior treatment with any investigational drug therapy within 30 days prior to screening
Subjects with active respiratory allergies or subjects expected to require anti-allergy medications during the study period for respiratory allergies
Known sensitivity to NTZ or any of the excipients comprising the NTZ tablets
Subjects unable to take oral medications
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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Nitazoxanide	Nitazoxanide	Two Nitazoxanide 300 mg tablets orally twice daily for 5 days
Placebo	Placebo	Two placebo tablets orally twice daily for 5 days

Primary Outcome Measures

Name	Time	Method
Time From First Dose to Symptom Response Over 21 Days of Follow up Based Upon the FLU-PRO Instrument (Novel Endpoint)	Up to 21 days	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.

Secondary Outcome Measures

Name	Time	Method
Time From First Dose to Ability to Perform All Normal Activities	Up to 21 days	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.
Proportions Experiencing Complications of EV/RV Infection	28 days	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.