Trial · NCT03605862
Efficacy and Safety of Nitazoxanide in the Treatment of Colds Due to Enterovirus/Rhinovirus Infection
NCT03605862, Phase 3, Completed, Romark Laboratories L.C.; results first posted 2022-04-14
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. Efficacy and Safety of Nitazoxanide in the Treatment of Colds Due to Enterovirus/Rhinovirus Infection. Trials, record NCT03605862. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT03605862
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- Efficacy and Safety of Nitazoxanide in the Treatment of Colds Due to Enterovirus/Rhinovirus Infection
- NCT number
- NCT03605862
- Status
- Completed
- Phases
- Phase 3
- Enrollment
- 1,756 participants, actual
- Lead sponsor
- Romark Laboratories L.C.
- Conditions
- Enterovirus, Rhinovirus
- Interventions
- Nitazoxanide, Placebo
- First posted
- 2018-07-30
- Last updated
- 2022-04-14
- Results first posted
- 2022-04-14
- Limitations and caveats
This study used a novel primary endpoint that was weakly correlated (r=0.43) with the anchor assessment of usual health, resulting in a primary analysis of questionable interpretability. The post-hoc analysis of Time to Sustained Recovery may be a more reliable endpoint given consistency with other endpoints (time to return to usual health, proportions experiencing complications, proportions positive for EV/RV).
Source ClinicalTrials.gov
Registered outcomes7
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | 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 | 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. |
| Secondary | 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. |
| Other | Time to Return to Usual Health | 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. |
| Other | Proportion Positive for EV/RV by RT-PCR at Days 2, 3 and 7 | 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. |
| Other | Analysis of Change From Baseline to Days 2, 3 and 7 in EV/RV Virus Titer | 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. |
| Other | Response Misclassification Rate Compared to Usual Health | 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. |
Source ClinicalTrials.gov
Outcomes11
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | 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 | The primary efficacy (intent-to-treat infected, ITTI) population consisted of 584 subjects (N=286 in NTZ group, N=298 in Placebo group) with laboratory-confirmed Enterovirus/Rhinovirus (EV/RV) infection. | hours | MEDIAN |
| SECONDARY | Time From First Dose to Ability to Perform All Normal Activities | Up to 21 days | The efficacy (intent-to-treat infected, ITTI) population consisted of 584 subjects (N=286 in NTZ group, N=298 in Placebo group) with laboratory-confirmed Enterovirus/Rhinovirus (EV/RV) infection. | hours | MEDIAN |
| SECONDARY | Proportions Experiencing Complications of EV/RV Infection | 28 days | The efficacy (intent-to-treat infected, ITTI) population consisted of 584 subjects (N=286 in NTZ group, N=298 in Placebo group) with laboratory-confirmed Enterovirus/Rhinovirus (EV/RV) infection. | Participants | COUNT_OF_PARTICIPANTS |
| OTHER_PRE_SPECIFIED | Time to Return to Usual Health | 21 days | The efficacy (intent-to-treat infected, ITTI) population consisted of 584 subjects (N=286 in NTZ group, N=298 in Placebo group) with laboratory-confirmed Enterovirus/Rhinovirus (EV/RV) infection. | hours | MEDIAN |
| OTHER_PRE_SPECIFIED | Proportion Positive for EV/RV by RT-PCR at Days 2, 3 and 7 | Days 2, 3, and 7 | The efficacy (intent-to-treat infected, ITTI) population consisted of 584 subjects (N=286 in NTZ group, N=298 in Placebo group) with laboratory-confirmed Enterovirus/Rhinovirus (EV/RV) infection. | proportion of participants | NUMBER |
| OTHER_PRE_SPECIFIED | Analysis of Change From Baseline to Days 2, 3 and 7 in EV/RV Virus Titer | Days 2, 3, and 7 | Analysis population includes subjects with laboratory-confirmed EV/RV who were positive for EV/RV at the preceding swab collection time point. Per protocol, day 2 and 3 visits were optional. | log10 RNA copies/mL | MEAN |
| OTHER_PRE_SPECIFIED | Response Misclassification Rate Compared to Usual Health | 21 days | The intent-to-treat-infected (ITTI) population consisted of all subjects positive for EV/RV at Baseline. Per the Statistical Analysis Plan, the response definition misclassification rate was to be calculated prior to unblinding including all data for subjects in the ITTI population. | n diaries misclassified/n diaries | NUMBER |
| POST_HOC | Correlation Coefficient for Sustained Response and Return to Usual Health | 21 days | The intent-to-treat-infected (ITTI) population consisted of all subjects positive for EV/RV at Baseline. Consistent with calculation of the response definition misclassification rate, the correlation coefficient was calculated for all subjects in the ITTI population regardless of treatment group assignment. | correlation coefficient | NUMBER |
| POST_HOC | Time to Return to Usual Health, Modified ITTI Population | 21 days | Modified ITTI population consists of 387 subjects with laboratory-confirmed EV/RV infection and 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. Assessment was completed via the Baseline FLU-PRO questionnaire. | hours | MEDIAN |
| POST_HOC | Time to Sustained Clinical Recovery | 21 days | The efficacy (intent-to-treat infected, ITTI) population consisted of 584 subjects (N=286 in NTZ group, N=298 in Placebo group) with laboratory-confirmed Enterovirus/Rhinovirus (EV/RV) infection. | hours | MEDIAN |
1 to 10 of 11Source ClinicalTrials.gov
See all 11 outcomesResults by group28
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Time From First Dose to Symptom Response Over 21 Days of Follow up Based Upon the FLU-PRO Instrument (Novel Endpoint) | Nitazoxanide | 122.5 | Inter-Quartile Range 58 to 244 | hours | |
| Time From First Dose to Symptom Response Over 21 Days of Follow up Based Upon the FLU-PRO Instrument (Novel Endpoint) | Placebo | 137.1 | Inter-Quartile Range 75 to 243 | hours | |
| Time From First Dose to Ability to Perform All Normal Activities | Nitazoxanide | 174.3 | Inter-Quartile Range 80 to 340 | hours | |
| Time From First Dose to Ability to Perform All Normal Activities | Placebo | 175.4 | Inter-Quartile Range 105 to 318 | hours | |
| Proportions Experiencing Complications of EV/RV Infection | Nitazoxanide | 12 | Participants | ||
| Proportions Experiencing Complications of EV/RV Infection | Placebo | 20 | Participants | ||
| Time to Return to Usual Health | Nitazoxanide | 154.1 | Inter-Quartile Range 80 to 320 | hours | |
| Time to Return to Usual Health | Placebo | 174.9 | Inter-Quartile Range 104 to 345 | hours | |
| Proportion Positive for EV/RV by RT-PCR at Days 2, 3 and 7 | Nitazoxanide | Day 2 | 0.81 | proportion of participants | |
| Proportion Positive for EV/RV by RT-PCR at Days 2, 3 and 7 | Placebo | Day 2 | 0.81 | proportion of participants |
1 to 10 of 28Source ClinicalTrials.gov
See all 28 results by groupParticipant flow6
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Overall Study | STARTED | Nitazoxanide | 872 | |
| Overall Study | STARTED | Placebo | 884 | |
| Overall Study | COMPLETED | Nitazoxanide | 844 | |
| Overall Study | COMPLETED | Placebo | 858 | |
| Overall Study | NOT COMPLETED | Nitazoxanide | 28 | |
| Overall Study | NOT COMPLETED | Placebo | 26 |
Source ClinicalTrials.gov
Adverse events18
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Chromaturia | Renal and urinary disorders | Nitazoxanide | 153 | 872 | |
| other | Chromaturia | Renal and urinary disorders | Placebo | 10 | 884 | |
| other | Diarrhoea | Gastrointestinal disorders | Nitazoxanide | 53 | 872 | |
| other | Diarrhoea | Gastrointestinal disorders | Placebo | 38 | 884 | |
| other | Nausea | Gastrointestinal disorders | Nitazoxanide | 24 | 872 | |
| other | Nausea | Gastrointestinal disorders | Placebo | 19 | 884 | |
| serious | Cardiac failure congestive | Cardiac disorders | Nitazoxanide | 1 | 872 | 1 |
| serious | Cardiac failure congestive | Cardiac disorders | Placebo | 0 | 884 | 0 |
| serious | Cholelithiasis | Hepatobiliary disorders | Nitazoxanide | 1 | 872 | 1 |
| serious | Cholelithiasis | Hepatobiliary disorders | Placebo | 0 | 884 | 0 |
1 to 10 of 18Source ClinicalTrials.gov
See all 18 adverse eventsAdverse event totals6
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Nitazoxanide | 0 | 872 |
| Total, all-cause mortality | Placebo | 0 | 884 |
| Total, other adverse events | Nitazoxanide | 200 | 872 |
| Total, other adverse events | Placebo | 58 | 884 |
| Total, serious adverse events | Nitazoxanide | 4 | 872 |
| Total, serious adverse events | Placebo | 1 | 884 |
Source ClinicalTrials.gov
Papers0
The papers the trial lists on ClinicalTrials.gov.
None in this release.
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons3
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
| Comparison | Source |
|---|---|
| Nitazoxanide vs Placebo: Proportions Experiencing Complications of EV/RV Infection | Trial comparisons |
| Nitazoxanide vs Placebo: deaths from any cause | Trial comparisons |
| Nitazoxanide vs Placebo: serious adverse events | Trial comparisons |
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
For software
Read this trial from software.
The record and each of its lists are JSON, twenty rows a page. No key.
GET https://conductscience.org/api/trials/v1/NCT03605862
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