Trial · NCT01227967
Comparing the Efficacy, Safety, and Tolerability of Combination Antivirals (Amantadine, Ribavirin, Oseltamivir) Versus Oseltamivir for the Treatment of Influenza in Adults at Risk for Complications
NCT01227967, Phase 2, Completed, National Institute of Allergy and Infectious Diseases (NIAID); results first posted 2017-07-11
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. Comparing the Efficacy, Safety, and Tolerability of Combination Antivirals (Amantadine, Ribavirin, Oseltamivir) Versus Oseltamivir for the Treatment of Influenza in Adults at Risk for Complications. Trials, record NCT01227967. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT01227967
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- Comparing the Efficacy, Safety, and Tolerability of Combination Antivirals (Amantadine, Ribavirin, Oseltamivir) Versus Oseltamivir for the Treatment of Influenza in Adults at Risk for Complications
- NCT number
- NCT01227967
- Status
- Completed
- Phases
- Phase 2
- Enrollment
- 881 participants, actual
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Conditions
- Influenza
- Interventions
- Amantadine, Ribavirin, Oseltamivir, Oseltamivir
- First posted
- 2010-10-25
- Last updated
- 2019-02-04
- Results first posted
- 2017-07-11
Source ClinicalTrials.gov
Registered outcomes15
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Percentage of Participants With Virus Detectable by Quantitative PCR (qPCR) in Nasopharyngeal (NP) Swabs | At Day 3 | The central laboratory performed a qualitative PCR test on the NP sample from Day 0 in order to confirm influenza infection and to determine the influenza type and subtype. For participants with a positive influenza test result at Day 0 from this qualitative PCR testing, the laboratory then performed qPCR testing of subsequent samples to quantify viral shedding. |
| Secondary | Number of Participants by Virus Detection Status | At Day 0, 3 and 7. | Number of participants who had undetectable values (less than the limit of detection \[LOD\]), who had values between the LOD and the lower limit of quantification (LLOQ), and who had values ≥LLOQ |
| Secondary | qPCR Viral Shedding | At Day 0, 3 and 7 | Median, 25% and 75% percentile of the value of viral shedding (Results \<LOD were imputed as the LOD value, and Results \>= LOD, \<LLOQ were imputed as the LLOQ value.) |
| Secondary | Number of Participants Shedding Virus | At day 3 and 7. | Number of participants with undetectable viral load at both Day 3 and Day 7; detectable at Day 3 and undetectable at Day 7; detectable at Day 7 (irrespective of whether or not detectable at Day 3). |
| Secondary | Time to Alleviation of Influenza Clinical Symptoms. | From treatment initiation to Day 28 | The assessed symptoms were cough, nasal obstruction (stuffy nose), sore throat, fatigue, headache, muscle aches, feverishness, rhinorrhea, nausea, vomiting, diarrhea. Duration of clinical symptoms is defined as the time from Day 0 to the first of two successive measurements at which all clinical symptoms are grade 0 (absent) or 1 (mild). A measurement is considered to be the 8AM or 8PM assessment during Days 0 to 7 (so two measurements are obtained per day) and then the daily assessment thereafter. Time will then be calculated in half-days through to Day 7. If a subject's first two assessments on (baseline assessment and first subsequent diary card assessment) satisfy this criterion, then the duration will be set to zero. For participants who did not have two successive records meeting this criterion, follow-up was censored for analysis purposes at the time of the last but one diary card record with symptoms evaluated. |
| Secondary | Time to Absence of Fever | From treatment initiation to Day 28 | Fever was considered present based on the diary cards if a subject reported a maximal temperature ≥38.0°C (for the period since the diary card was previously completed) or reported having taken an antipyretic drug (also for the period since the diary card was previously completed). Otherwise, fever was considered not present during the period since the diary card was previously completed, except that the evaluation was considered missing if either the temperature or the antipyretic drug use entry was not completed on the diary card. The duration of fever was defined as the time from Day 0 to the first of two successive assessments (through to Day 7) or to the first assessment (Day 8 onwards) at which no fever was present according to this definition.For participants who did not have two successive records meeting this criterion, follow-up was censored for analysis purposes at the time of the last but one diary card record with fever evaluated. |
| Secondary | Time to Resolution of All Symptoms AND Fever | From treatment initiation to Day 28 | The assessed symptoms were cough, nasal obstruction (stuffy nose), sore throat, fatigue, headache, muscle aches, feverishness, rhinorrhea, nausea, vomiting, diarrhea. Fever was considered present based on the diary cards if a subject reported a maximal temperature ≥38.0°C (for the period since the diary card was previously completed) or reported having taken an antipyretic drug (also for the period since the diary card was previously completed). Time to resolution of all clinical symptoms and fever is defined as the time from Day 0 to the first of two successive measurements at which all clinical symptoms are grade 0 (absent) or 1(mild) and no fever \>=38.0 C or antipyretic drug is reported. For participants who did not have two successive records meeting this criterion, follow-up was censored for analysis purposes at the time of the last but one diary card record with symptoms and fever evaluated. |
| Secondary | Time to Feeling as Good as Before the Onset of the Influenza Illness | From treatment initiation to Day 28 | Time to feeling as good as before influenza is defined as time to the first of two successive 'yes' responses to the question of 'feeling as good as you did before you had the flu'.For participants who did not have two successive records meeting this criterion, follow-up was censored for analysis purposes at the time of the last but one diary card record with question answered. |
| Secondary | Time to Return to Pre-influenza Function | From treatment initiation to Day 28 | Time to return to pre-influenza function is defined as the time from Day 0 to the first of two successive 'Yes' answers to the global assessment question 'Are you functioning as well as you were before you had the flu'.For participants who did not have two successive records meeting this criterion, follow-up was censored for analysis purposes at the time of the last but one diary card record with question answered. |
| Secondary | Time to Return of Physical Function to Pre-illness Leve | From treatment initiation to Day 28 | Time to return of physical function to pre-illness level was defined as the time from Day 0 to the first of two successive measurements at which the physical function score equals or is better than the pre-illness score (obtained by recall at enrollment).For subjects who did not have two successive records meeting this criterion, follow-up was censored for analysis purposes at the time of the last but one diary card record with physical function evaluated. |
1 to 10 of 15Source ClinicalTrials.gov
See all 15 registered outcomesOutcomes15
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Percentage of Participants With Virus Detectable by Quantitative PCR (qPCR) in Nasopharyngeal (NP) Swabs | At Day 3 | The population analyzed was restricted to the 407 participants who had a confirmed positive test for influenza by qPCR in the central laboratory testing and were not in the pilot study for IRC003. 13 participants (5 in the Combination Therapy and 8 in the Oseltamivir Monotherapy) had missing endpoint samples so were excluded from the analysis. | percentage of participants analyzed | NUMBER |
| SECONDARY | Number of Participants by Virus Detection Status | At Day 0, 3 and 7. | The population analyzed is the Primary Efficacy Population (PEP), which included all participants who were randomized properly, had received at least one dose of study drug, and had influenza virus isolated and typed in the qualitative PCR evaluation at Day 0 from central laboratory testing. | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | qPCR Viral Shedding | At Day 0, 3 and 7 | The population analyzed is the Primary Efficacy Population (PEP), which included all participants who were randomized properly, had received at least one dose of study drug, and had influenza virus isolated and typed in the qualitative PCR evaluation at Day 0 from central laboratory testing. | Log10 copies/mL | MEDIAN |
| SECONDARY | Number of Participants Shedding Virus | At day 3 and 7. | The population analyzed is the Primary Efficacy Population (PEP), which included all participants who were randomized properly, had received at least one dose of study drug, and had influenza virus isolated and typed in the qualitative PCR evaluation at Day 0 from central laboratory testing. | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Time to Alleviation of Influenza Clinical Symptoms. | From treatment initiation to Day 28 | The population analyzed is the Intention To Treat (ITT) Population, which included all participants who were randomized properly and who had received at least one dose of study drug. | Days | MEDIAN |
| SECONDARY | Time to Absence of Fever | From treatment initiation to Day 28 | The population analyzed is the Intention To Treat (ITT) Population, which included all participants who were randomized properly and who had received at least one dose of study drug. | Days | MEDIAN |
| SECONDARY | Time to Resolution of All Symptoms AND Fever | From treatment initiation to Day 28 | The population analyzed is the Intention To Treat (ITT) Population, which includes all participants who were randomized properly and who had received at least one dose of study drug. | Days | MEDIAN |
| SECONDARY | Time to Feeling as Good as Before the Onset of the Influenza Illness | From treatment initiation to Day 28 | The population analyzed is the Intention To Treat (ITT) Population, which included all participants who were randomized properly and who had received at least one dose of study drug. | Days | MEDIAN |
| SECONDARY | Time to Return to Pre-influenza Function | From treatment initiation to Day 28 | The population analyzed is the Intention To Treat (ITT) Population, which included all participants who were randomized properly and who had received at least one dose of study drug. | Days | MEDIAN |
| SECONDARY | Time to Return of Physical Function to Pre-illness Leve | From treatment initiation to Day 28 | The population analyzed is the Intention To Treat (ITT) Population, which included all participants who were randomized properly and who had received at least one dose of study drug. | Days | MEDIAN |
1 to 10 of 15Source ClinicalTrials.gov
See all 15 outcomesResults by group72
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Percentage of Participants With Virus Detectable by Quantitative PCR (qPCR) in Nasopharyngeal (NP) Swabs | Combination Therapy | 40 | percentage of participants analyzed | ||
| Percentage of Participants With Virus Detectable by Quantitative PCR (qPCR) in Nasopharyngeal (NP) Swabs | Oseltamivir Monotherapy | 50 | percentage of participants analyzed | ||
| Number of Participants by Virus Detection Status | Combination Therapy | Day 0 / >=LLOQ | 221 | Participants | |
| Number of Participants by Virus Detection Status | Oseltamivir Monotherapy | Day 0 / >=LLOQ | 200 | Participants | |
| Number of Participants by Virus Detection Status | Combination Therapy | Day 0 / >=LOD, <LLOQ | 4 | Participants | |
| Number of Participants by Virus Detection Status | Oseltamivir Monotherapy | Day 0 / >=LOD, <LLOQ | 9 | Participants | |
| Number of Participants by Virus Detection Status | Combination Therapy | Day 0 / <LOD | 5 | Participants | |
| Number of Participants by Virus Detection Status | Oseltamivir Monotherapy | Day 0 / <LOD | 15 | Participants | |
| Number of Participants by Virus Detection Status | Combination Therapy | Day 0 / Missing | 0 | Participants | |
| Number of Participants by Virus Detection Status | Oseltamivir Monotherapy | Day 0 / Missing | 0 | Participants |
1 to 10 of 72Source ClinicalTrials.gov
See all 72 results by groupParticipant flow6
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Overall Study | STARTED | Combination Therapy | 314 | |
| Overall Study | STARTED | Oseltamivir Monotherapy | 316 | |
| Overall Study | COMPLETED | Combination Therapy | 298 | |
| Overall Study | COMPLETED | Oseltamivir Monotherapy | 303 | |
| Overall Study | NOT COMPLETED | Combination Therapy | 16 | |
| Overall Study | NOT COMPLETED | Oseltamivir Monotherapy | 13 |
Source ClinicalTrials.gov
Adverse events62
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 | Combination Therapy | 40 | 314 | |
| other | Diarrhoea | Gastrointestinal disorders | Oseltamivir Monotherapy | 52 | 312 | |
| other | Nausea | Gastrointestinal disorders | Combination Therapy | 52 | 314 | |
| other | Nausea | Gastrointestinal disorders | Oseltamivir Monotherapy | 50 | 312 | |
| other | Vomiting | Gastrointestinal disorders | Combination Therapy | 34 | 314 | |
| other | Vomiting | Gastrointestinal disorders | Oseltamivir Monotherapy | 22 | 312 | |
| other | Fatigue | General disorders | Combination Therapy | 18 | 314 | |
| other | Fatigue | General disorders | Oseltamivir Monotherapy | 12 | 312 | |
| other | Pyrexia | General disorders | Combination Therapy | 16 | 314 | |
| other | Pyrexia | General disorders | Oseltamivir Monotherapy | 18 | 312 |
1 to 10 of 62Source ClinicalTrials.gov
See all 62 adverse eventsAdverse event totals6
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Combination Therapy | 0 | 314 |
| Total, all-cause mortality | Oseltamivir Monotherapy | 1 | 312 |
| Total, other adverse events | Combination Therapy | 148 | 314 |
| Total, other adverse events | Oseltamivir Monotherapy | 163 | 312 |
| Total, serious adverse events | Combination Therapy | 14 | 314 |
| Total, serious adverse events | Oseltamivir Monotherapy | 6 | 312 |
Source ClinicalTrials.gov
Papers4
The papers the trial lists on ClinicalTrials.gov.
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 |
|---|---|
| Combination Therapy vs Oseltamivir Monotherapy: 28-day Mortality | Trial comparisons |
| Combination Therapy vs Oseltamivir Monotherapy: deaths from any cause | Trial comparisons |
| Combination Therapy vs Oseltamivir Monotherapy: 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.
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Read this trial from software.
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