A Phase 2 interventional study of Oseltamivir in Influenza, Avian Influenza and Severe Influenza, sponsored by National Institute of Allergy and Infectious Diseases (NIAID). Completed at 12 sites in 3 countries. Open to participants aged 1 Year and older. Per ClinicalTrials.gov, last updated 2014-06-06.
Sponsored by National Institute of Allergy and Infectious Diseases (NIAID) · Phase 2, Interventional, and Treatment
Influenza, also known as the flu, is a contagious respiratory illness caused by influenza viruses. The illness can range in severity, from mild to severe to even death, and it causes an estimated 500,000 to 1,000,000 deaths worldwide each year. In the last several years, there have been increasing numbers of human cases of avian influenza, or bird flu. This trend may pose a threat of a future pandemic--worldwide outbreak of disease--with an avian influenza virus that can easily spread from person to person. Oseltamivir is an antiviral medication that is used to treat people with uncomplicated human influenza, and it may be effective in treating people with either severe human influenza or avian influenza. The purpose of this international study is to compare standard-dose oseltamivir versus high-dose oseltamivir for treating people who are hospitalized with severe human influenza or avian influenza.
Two main types of influenza virus--Types A and B--are responsible for the seasonal flu epidemics that occur each year. The influenza A viruses can be broken down into subtypes based on two proteins on the surface of the virus: hemagglutinin (H) and neuraminidase (N). The A subtypes usually found in humans are H1N1, H1N2, and H3N2. Other A subtypes are found primarily in animals. For example, the "avian influenza virus" refers to an influenza A virus that is found chiefly in birds.
Although avian influenza does not usually affect humans, increasing numbers of cases of human infection from avian influenza virus H5N1 have been reported in the last several years. Because all influenza viruses have the ability to modify, there is concern that this trend of increasing cases may pose a threat of a future pandemic with a new H5N1 virus that could spread easily from person to person.
The H5N1 virus that has caused human infection in Asia is resistant to amantadine and rimantadine, two antiviral medications commonly used for treating people with influenza. Another antiviral medication, oseltamivir, is currently used to treat people with uncomplicated human influenza. The purpose of this study is to compare standard-dose oseltamivir and high-does oseltamivir for treating people who are hospitalized with severe human influenza or avian influenza. The study will also attempt to identify how severe human influenza and avian influenza differ in the following factors: clinical manifestation, relationship between antiviral plasma concentrations and viral dynamics, and pathogenesis.
Upon meeting certain screening criteria, participants will be randomly assigned to receive oseltamivir either at a standard-dose level (75 mg twice daily orally or equivalent dose adjusted for age, weight, and kidney function) or at a high-dose level (150 mg twice daily orally or equivalent dose adjusted for age, weight, and kidney function). Treatment will continue for 5 days, after which participants who meet clinical failure criteria will continue their assigned treatment for an additional 5 days. It is anticipated that participants will remain hospitalized through the course of treatment. On Day 0, which marks the first day of hospitalization, participants will undergo a medical review, physical examination, blood sampling, nasal swab, throat swab, anal swab, and chest x-ray. An endotracheal aspirate procedure and urine sampling may also be performed. During the hospital stay, most of the above procedures will be repeated regularly, and additional samples of lung fluid, cerebral spinal fluid, and pleural fluid may be obtained. On Day 5 and possibly on Day 10, participants will undergo a follow-up x-ray. If applicable, participants will attend outpatient study visits on Days 10, 14, and 28 for further evaluation; participants with avian influenza will also attend visits on Days 56 and 180.
2,264 studies on the registry are indexed under Influenza, Human; 173 are open to participants now.
This study's enrollment of 326 is above the median of 240 across 1,894 interventional studies indexed under Influenza, Human.
Browse Influenza, Human studies →National Institute of Allergy and Infectious Diseases (NIAID) is the lead sponsor of 2,445 studies on the registry; 182 are open to participants now.
Of its 402 completed or terminated interventional studies of FDA-regulated products, 300 (75%) have results posted.
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Severe influenza infection criteria:
One of the following:
Avian influenza infection criteria:
Exclusion Criteria:
All participants \>= 15 years will receive standard-dose oseltamivir (75 mg twice daily orally or equivalent dose adjusted for age, weight, and kidney function) for 5 to 10 days.
Drug: Oseltamivir
All participants \>= 15 years will receive high-dose oseltamivir (150 mg twice daily orally or equivalent dose adjusted for age, weight, and kidney function) for 5 to 10 days.
Drug: Oseltamivir
All participants \<15 years will receive standard-dose oseltamivir (75 mg twice daily orally or equivalent dose adjusted for age, weight, and kidney function) for 5 to 10 days.
Drug: Oseltamivir
All Participants \<15 years will receive high-dose oseltamivir (150 mg twice daily orally or equivalent dose adjusted for age, weight, and kidney function) for 5 to 10 days.
Drug: Oseltamivir
Oseltamivir is a sialic acid analogue that potently and specifically inhibits the viral neuraminidases by competitively and reversibly interacting with the active enzyme site of influenza A and B viruses. Oseltamivir will be administered orally in standard formulations (capsules for adults and children at least 15 years of age; suspension for children younger than 15 years).
Also known as: Tamiflu
Proportion of All Participants Negative for Viral RNA on Day 5
Proportion of all participants with no detectable viral RNA by reverse transcriptase-polymerase chain reaction (RT-PCR) in a combined nasal and throat swab sample on day 5.
Time frame: After 5 days of treatment
Participants Meeting Criteria for Day 5 Clinical Failure
Proportion of participants that have clinical failure by day 5. Subjects that meet one of the following on Day 5 will be classified as a clinical failure: * Severe tachypnea (respiratory rate ≥ 30 for ages ≥12 years, rate ≥ 40 for ages 6 to 12 years, rate ≥45 for ages 3 to 6 years, rate ≥ 50 for ages 1 to 3 years) * Severe dyspnea (unable to speak full sentences, or use of accessory respiratory muscles) * Arterial oxygen saturation ≤92% on room air by trans-cutaneous method * Need for mechanical ventilation or intensive care unit (ICU) admission For the purpose of endpoint definition, death prior to or on Day 5 will also be considered a clinical failure at Day 5.
Time frame: After 5 days of treatment
In-hospital Mortality Rates
Standard therapy with oseltamivir is five days. Those patients with persistent symptoms on day five were continued on the randomized dose for an additional five days and assessments were performed up to day 10.
Time frame: After up to 10 days of treatment
Median Time (Days) Receipt of Oxygen
Time frame: Throughout study, 14 days
Median Time (Days) in ICU
Time frame: Throughout study, 14 days
Median Time (Days) on Ventilation
Use of mechanical ventilation at any time for subjects with severe influenza and avian influenza.
Time frame: Throughout study, 14 days
| Milestone | Standard Dose Oseltamivir Adult Cohort | Double Dose Oseltamivir Adult Cohort | Standard Dose Oseltamivir Child Cohort | Double Dose Oseltamivir Child Cohort |
|---|---|---|---|---|
| Started | 39 | 41 | 122 | 124 |
| Completed | 39 | 41 | 122 | 124 |
| Not completed | 0 | 0 | 0 | 0 |
Proportion of all participants with no detectable viral RNA by reverse transcriptase-polymerase chain reaction (RT-PCR) in a combined nasal and throat swab sample on day 5.
| participants | Double Dose Oseltamivir | Standard Dose Oseltamivir |
|---|---|---|
| Proportion of All Participants Negative for Viral RNA on Day 5 | 115 | 105 |
Proportion of participants that have clinical failure by day 5. Subjects that meet one of the following on Day 5 will be classified as a clinical failure: * Severe tachypnea (respiratory rate ≥ 30 for ages ≥12 years, rate ≥ 40 for ages 6 to 12 years, rate ≥45 for ages 3 to 6 years, rate ≥ 50 for ages 1 to 3 years) * Severe dyspnea (unable to speak full sentences, or use of accessory respiratory muscles) * Arterial oxygen saturation ≤92% on room air by trans-cutaneous method * Need for mechanical ventilation or intensive care unit (ICU) admission For the purpose of endpoint definition, death prior to or on Day 5 will also be considered a clinical failure at Day 5.
| participants | Double Dose Oseltamivir | Standard Dose Oseltamivir |
|---|---|---|
| Participants Meeting Criteria for Day 5 Clinical Failure | 16 | 20 |
Standard therapy with oseltamivir is five days. Those patients with persistent symptoms on day five were continued on the randomized dose for an additional five days and assessments were performed up to day 10.
| participants | Double Dose Oseltamivir | Standard Dose Oseltamivir |
|---|---|---|
| In-hospital Mortality Rates | 12 | 9 |
| days | Double Dose Oseltamivir | Standard Dose Oseltamivir |
|---|---|---|
| Median Time (Days) Receipt of Oxygen | 3 ± 2-5 | 3.5 ± 2-7 |
| days | Double Dose Oseltamivir | Standard Dose Oseltamivir |
|---|---|---|
| Median Time (Days) in ICU | 4.4 (3 to 6) | 5 (2 to 11) |
Use of mechanical ventilation at any time for subjects with severe influenza and avian influenza.
| days | Double Dose Oseltamivir | Standard Dose Oseltamivir |
|---|---|---|
| Median Time (Days) on Ventilation | 2.5 (1 to 16) | 5 (2 to 11) |
Collected over Through Day 28 for severe influenza, and Day 180 for avian influenza.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Double Dose Oseltamivir | — | 1/165 (0.6%) | 37/165 (22.4%) |
| Standard Dose Oseltamivir | — | 0/161 (0%) | 38/161 (23.6%) |
| Event | Double Dose Oseltamivir | Standard Dose Oseltamivir |
|---|---|---|
| Septic shockRespiratory, thoracic and mediastinal disorders | 1/165 | 0/161 |
| Event | Double Dose Oseltamivir | Standard Dose Oseltamivir |
|---|---|---|
| otherGeneral disorders | 10/165 | 11/161 |
| respiratory failureRespiratory, thoracic and mediastinal disorders | 10/165 | 5/161 |
| diarrheaGastrointestinal disorders | 2/165 | 9/161 |
| multi-organ failuresGeneral disorders | 3/165 | 3/161 |
| ThrombocytosisBlood and lymphatic system disorders | 3/165 | 0/161 |
| pneumothoraxRespiratory, thoracic and mediastinal disorders | 1/165 | 2/161 |
| BronchitisRespiratory, thoracic and mediastinal disorders | 0/165 | 2/161 |
| Septic shockCardiac disorders | 1/165 | 2/161 |
| acute respiratory distress syndromeRespiratory, thoracic and mediastinal disorders | 2/165 | 1/161 |
| neutropeniaBlood and lymphatic system disorders | 2/165 | 1/161 |
All participants that were randomized
| Age, Customized(participants) | Standarad Dose Oseltamivir | Double Dose Oseltamivir | Total |
|---|---|---|---|
| Child cohort: ≥1 to <15 years | 122 | 124 | 246 |
| Adult cohort: ≥15 years | 39 | 41 | 80 |
| Sex: Female, Male(Participants) | Standarad Dose Oseltamivir | Double Dose Oseltamivir | Total |
|---|---|---|---|
| Female | 72 | 69 | 141 |
| Male | 89 | 96 | 185 |
This study is completed, as verified in May 2014. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Oseltamivir
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