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NCT03605862

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

Completed Phase 3 Results posted Last updated 14 April 2022
What this trial tests

Phase 3 trial testing Nitazoxanide in Enterovirus in 1,756 participants. Completed in 4 February 2019.

Timeline
11 September 2018
Primary endpoint
4 February 2019
4 February 2019

Quick facts

Lead sponsorRomark Laboratories L.C.
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingtriple
Primary purposetreatment
Enrollment1,756
Start date11 September 2018
Primary completion4 February 2019
Estimated completion4 February 2019
Sites45 locations across Puerto Rico, United States

Drugs / interventions tested

Conditions studied

Sponsor

Romark Laboratories L.C. — full company profile →

Who can join

12 and older, any sex, with Enterovirus or Rhinovirus. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

GroupValue95% CI
Nitazoxanide122.558 – 244
Placebo137.175 – 243
Time From First Dose to Ability to Perform All Normal Activities Secondary · 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.

GroupValue95% CI
Nitazoxanide174.380 – 340
Placebo175.4105 – 318
Proportions Experiencing Complications of EV/RV Infection Secondary · 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.

GroupValue95% CI
Nitazoxanide12
Placebo20
Time to Return to Usual Health Secondary · 21 days

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.

GroupValue95% CI
Nitazoxanide154.180 – 320
Placebo174.9104 – 345
Proportion Positive for EV/RV by RT-PCR at Days 2, 3 and 7 Secondary · 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.

Day 2
GroupValue95% CI
Nitazoxanide0.81
Placebo0.81
Day 3
GroupValue95% CI
Nitazoxanide0.79
Placebo0.79
Day 7
GroupValue95% CI
Nitazoxanide0.66
Placebo0.76
Analysis of Change From Baseline to Days 2, 3 and 7 in EV/RV Virus Titer Secondary · Days 2, 3, and 7

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.

Day 2
GroupValue95% CI
Nitazoxanide-0.2203± 0.0934
Placebo-0.4186± 0.0884
Day 3
GroupValue95% CI
Nitazoxanide-0.5577± 0.1272
Placebo-0.8282± 0.1053
Day 7
GroupValue95% CI
Nitazoxanide-1.5113± 0.1373
Placebo-1.6470± 0.1231
Response Misclassification Rate Compared to Usual Health Secondary · 21 days

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.

GroupValue95% CI
ITTI Population0.21915
Correlation Coefficient for Sustained Response and Return to Usual Health Secondary · 21 days

The correlation coefficient between sustained response and return to usual health was calculated for the pooled ITTI population (i.e., not by treatment group) as a measure of association between the primary endpoint response definition and its intended anchor, patient-reported return to usual health.

GroupValue95% CI
ITTI Population0.43
Time to Return to Usual Health, Modified ITTI Population Secondary · 21 days

Examination of Baseline disease characteristics revealed many subjects reporting via the Baseline FLU-PRO questionnaire that they are at their usual state of health, that symptoms do not interfere with any usual activities, and/or that symptoms are already improving. The pre-specified analysis of Time to Return for Usual Health was repeated for the population with Baseline subject-reported assessment that symptoms are present, the symptoms are not consistent with the subject's usual health, the symptoms interfere with daily activities, and the symptoms have worsened or remained the same relati

GroupValue95% CI
Nitazoxanide153.796 – 317
Placebo195.0123 – 365
Time to Sustained Clinical Recovery Secondary · 21 days

Alternative means of endpoint construction were pursued to strengthen the relationship between symptoms-based endpoint measures and subject global assessments of health. Time to Sustained Clinical Recovery is an endpoint based on evidence of meaningful within-subject change sustained for the duration of the study. Time to Sustained Clinical Recovery is the time in hours from the first dose of study medication to the first time at which the subject reports a decrease in total FLU-PRO score from the previous diary with assessment that symptoms are at least "somewhat better than yesterday", no or

GroupValue95% CI
Nitazoxanide171.481 – 411
Placebo221.5103 – 504
Time to Sustained Clinical Recovery, Modified ITTI Population Secondary · 21 days

Analysis of Time to Sustained Clinical Recovery was repeated for the population with Baseline subject-reported assessment that symptoms are present, the symptoms are not consistent with the subject's usual health, the symptoms interfere with daily activities, and the symptoms have worsened or remained the same relative to the previous day. Time to Sustained Clinical Recovery is the time in hours from the first dose of study medication to the first time at which the subject reports a decrease in total FLU-PRO score from the previous diary with assessment that symptoms are at least "somewhat bet

GroupValue95% CI
Nitazoxanide150.381 – 322
Placebo244.1119 – 504

Adverse events — posted to ClinicalTrials.gov

Time frame: 28 days or until resolution of all adverse events, whichever occurred later.. Reporting threshold: 2%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Nitazoxanide
Serious: 4/872 (0%)
Deaths: 0/872
Placebo
Serious: 1/884 (0%)
Deaths: 0/884

Serious adverse events (6 terms)

ReactionSystemNitazoxanidePlacebo
Cardiac failure congestiveCardiac disorders
CholelithiasisHepatobiliary disorders
Gastroenteritis viralInfections and infestations
Post procedural infectionInfections and infestations
UrosepsisInfections and infestations
Status epilepticusNervous system disorders
Other adverse events (3 terms — click to expand)

ReactionSystemNitazoxanidePlacebo
ChromaturiaRenal and urinary disorders
DiarrhoeaGastrointestinal disorders
NauseaGastrointestinal disorders

Most-reported serious reactions: Cardiac failure congestive, Cholelithiasis, Gastroenteritis viral, Post procedural infection, Urosepsis, Status epilepticus.

Data from ClinicalTrials.gov NCT03605862 adverse events section.

Sponsor's own description

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

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Discovery and development of safe-in-man broad-spectrum antiviral agents.
    Andersen PI, Ianevski A, Lysvand H, Vitkauskiene A, et al · · 2020 · cited 174× · PMID 32081774 · DOI 10.1016/j.ijid.2020.02.018
  2. Efficacy and Safety of Nitazoxanide in Addition to Standard of Care for the Treatment of Severe Acute Respiratory Illness.
    Gamiño-Arroyo AE, Guerrero ML, McCarthy S, Ramírez-Venegas A, et al · · 2019 · cited 41× · PMID 30753384 · DOI 10.1093/cid/ciz100
  3. In silico molecular screening of bioactive natural compounds of rosemary essential oil and extracts for pharmacological potentials against rhinoviruses.
    Singh D, Mittal N, Mittal P, Tiwari N, et al · · 2024 · cited 5× · PMID 39075176 · DOI 10.1038/s41598-024-68450-3
  4. A comparative analysis of parechovirus protein structures with other picornaviruses.
    Domanska A, Guryanov S, Butcher SJ. · · 2021 · cited 5× · PMID 34315275 · DOI 10.1098/rsob.210008

Verify or expand the search:

Other trials of Nitazoxanide

Trials testing the same drug.

Other recruiting trials for Enterovirus

Currently open trials in the same condition.

Other Romark Laboratories L.C. trials

Trials by the same sponsor.

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