Trial · NCT03336619
A Phase III, Randomized, Double-Blind, Placebo Controlled Trial to Evaluate the Efficacy and Safety of Nitazoxanide in the Treatment of Uncomplicated Influenza
NCT03336619, Phase 3, Completed, Romark Laboratories L.C.; results first posted 2022-06-28
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. A Phase III, Randomized, Double-Blind, Placebo Controlled Trial to Evaluate the Efficacy and Safety of Nitazoxanide in the Treatment of Uncomplicated Influenza. Trials, record NCT03336619. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT03336619
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- A Phase III, Randomized, Double-Blind, Placebo Controlled Trial to Evaluate the Efficacy and Safety of Nitazoxanide in the Treatment of Uncomplicated Influenza
- NCT number
- NCT03336619
- Status
- Completed
- Phases
- Phase 3
- Enrollment
- 1,030 participants, actual
- Lead sponsor
- Romark Laboratories L.C.
- Conditions
- Influenza
- Interventions
- Nitazoxanide, Placebo
- First posted
- 2017-11-08
- Last updated
- 2022-06-28
- Results first posted
- 2022-06-28
- Limitations and caveats
Limitations of this study include inability to establish meaningfulness of the novel primary endpoint and selection of patients for whom the benefit of antiviral therapy may be marginal (e.g., vaccinated, antibody-positive, and subjects with improving illness at Baseline).
Source ClinicalTrials.gov
Registered outcomes6
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 | 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 | Number of Subjects Experiencing One or More Complications of Influenza | Up to 21 days | Complications of influenza infection included pneumonia, otitis media, bronchitis, sinusitis, worsening of pre-existing health conditions, systemic antibiotic use for infections secondary to influenza infection, hospitalization due to influenza or complications of influenza and death. |
| Secondary | Time to Symptom Response Excluding the FLU-PRO Gastrointestinal and Eye Domains | 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 25 FLU-PRO symptoms (excluding gastrointestinal and eye 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 25 symptom thresholds most closely associated with patient-reported usual health. |
| 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 of Diaries Misclassified by Novel Response Definition | 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
Outcomes12
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 | Up to 21 days | The ITTI (primary efficacy) population consisted of all subjects positive for influenza by RT-PCR at Baseline. | hours | MEDIAN |
| SECONDARY | Time From First Dose to Ability to Perform All Normal Activities | Up to 21 days | The ITTI (primary efficacy) population consisted of all subjects positive for influenza by RT-PCR at Baseline. | hours | MEDIAN |
| SECONDARY | Number of Subjects Experiencing One or More Complications of Influenza | Up to 21 days | The ITTI (primary efficacy) population consisted of all subjects positive for influenza by RT-PCR at Baseline | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Time to Symptom Response Excluding the FLU-PRO Gastrointestinal and Eye Domains | Up to 21 days | The ITTI (primary efficacy) population consisted of all subjects positive for influenza by RT-PCR at Baseline | hours | MEDIAN |
| OTHER_PRE_SPECIFIED | Time to Return to Usual Health | 21 days | The ITTI (primary efficacy) population consisted of all subjects positive for influenza by RT-PCR at Baseline. | hours | MEDIAN |
| OTHER_PRE_SPECIFIED | Proportion of Diaries Misclassified by Novel Response Definition | 21 days | The ITTI (primary efficacy) population consisted of all subjects positive for influenza by RT-PCR 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. | diaries | NUMBER |
| POST_HOC | Correlation Coefficient for Sustained Response and Return to Usual Health | 21 days | The correlation coefficient between sustained response and return to usual health was to be calculated prior to unblinding including all data for subjects in the ITTI population, consistent with the misclassification rate as specified in the statistical analysis plan. | correlation coefficient | NUMBER |
| POST_HOC | Time to Return to Usual Health, Placebo-Treated Subjects by Baseline Antibody Status | 21 days | Subjects with laboratory-confirmed influenza (ITTI population) who were randomized to the placebo treatment group by whether the subjects had detectable anti-influenza antibodies at Baseline. | hours | MEDIAN |
| POST_HOC | Time to Sustained Clinical Recovery | 21 days | The ITTI (primary efficacy) population consisted of all subjects positive for influenza by RT-PCR at Baseline. | hours | MEDIAN |
| POST_HOC | Time to Sustained Clinical Recovery by Antibody Status, Placebo-Treated Subjects | 21 days | Placebo-treated subjects with and without anti-influenza antibodies detected at Baseline who were positive for influenza by RT-PCR. | hours | MEDIAN |
1 to 10 of 12Source ClinicalTrials.gov
See all 12 outcomesResults by group22
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 | Nitazoxanide | 155.1 | Inter-Quartile Range 103.7 to 266.3 | hours | |
| Time From First Dose to Symptom Response | Placebo | 153.9 | Inter-Quartile Range 100.2 to 270.7 | hours | |
| Time From First Dose to Ability to Perform All Normal Activities | Nitazoxanide | 201.8 | Inter-Quartile Range 126.6 to 362.7 | hours | |
| Time From First Dose to Ability to Perform All Normal Activities | Placebo | 200.8 | Inter-Quartile Range 127.5 to 347.2 | hours | |
| Number of Subjects Experiencing One or More Complications of Influenza | Nitazoxanide | 50 | Participants | ||
| Number of Subjects Experiencing One or More Complications of Influenza | Placebo | 45 | Participants | ||
| Time to Symptom Response Excluding the FLU-PRO Gastrointestinal and Eye Domains | Nitazoxanide | 152.2 | Inter-Quartile Range 100.8 to 248.9 | hours | |
| Time to Symptom Response Excluding the FLU-PRO Gastrointestinal and Eye Domains | Placebo | 151.7 | Inter-Quartile Range 97.8 to 268.7 | hours | |
| Time to Return to Usual Health | Nitazoxanide | 176.6 | Inter-Quartile Range 120.0 to 315.0 | hours | |
| Time to Return to Usual Health | Placebo | 202.1 | Inter-Quartile Range 126.6 to 322.1 | hours |
1 to 10 of 22Source ClinicalTrials.gov
See all 22 results by groupParticipant flow8
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Overall Study | STARTED | Nitazoxanide | 515 | |
| Overall Study | STARTED | Placebo | 515 | |
| Overall Study | Positive for Influenza by RT-PCR at Baseline (Intent-to-treat Infected [ITTI] Population) | Nitazoxanide | 314 | |
| Overall Study | Positive for Influenza by RT-PCR at Baseline (Intent-to-treat Infected [ITTI] Population) | Placebo | 306 | |
| Overall Study | COMPLETED | Nitazoxanide | 301 | |
| Overall Study | COMPLETED | Placebo | 290 | |
| Overall Study | NOT COMPLETED | Nitazoxanide | 214 | |
| Overall Study | NOT COMPLETED | Placebo | 225 |
Source ClinicalTrials.gov
Adverse events12
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 | Diarrhoea | Gastrointestinal disorders | Nitazoxanide | 34 | 515 | 41 |
| other | Diarrhoea | Gastrointestinal disorders | Placebo | 25 | 515 | 26 |
| other | Chromaturia | Renal and urinary disorders | Nitazoxanide | 75 | 515 | 75 |
| other | Chromaturia | Renal and urinary disorders | Placebo | 5 | 515 | 5 |
| other | Nausea | Gastrointestinal disorders | Nitazoxanide | 8 | 515 | 8 |
| other | Nausea | Gastrointestinal disorders | Placebo | 13 | 515 | 13 |
| serious | Procedural pneumothorax | Injury, poisoning and procedural complications | Nitazoxanide | 1 | 515 | 1 |
| serious | Procedural pneumothorax | Injury, poisoning and procedural complications | Placebo | 0 | 515 | 0 |
| serious | Typhus | Infections and infestations | Nitazoxanide | 0 | 515 | 0 |
| serious | Typhus | Infections and infestations | Placebo | 1 | 515 | 1 |
1 to 10 of 12Source ClinicalTrials.gov
See all 12 adverse eventsAdverse event totals6
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Nitazoxanide | 1 | 515 |
| Total, all-cause mortality | Placebo | 0 | 515 |
| Total, other adverse events | Nitazoxanide | 107 | 515 |
| Total, other adverse events | Placebo | 36 | 515 |
| Total, serious adverse events | Nitazoxanide | 2 | 515 |
| Total, serious adverse events | Placebo | 1 | 515 |
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: Number of Subjects Experiencing One or More Complications of Influenza | 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/NCT03336619
GET https://conductscience.org/api/trials/v1/NCT03336619/results?page=2