A Randomized Double-Blind Study Comparing Oseltamivir Versus Placebo for the Treatment of Influenza in Low Risk Adults
Overview
- Phase
- Not Applicable
- Status
- Completed
- Enrollment
- 716
- Locations
- 47
- Primary Endpoint
- Percentage of Participants With Virus Detectable by Quantitative PCR (qPCR) in Nasopharyngeal (NP) Swabs at Day 3 -- Team Collected Samples
Overview
Brief Summary
People who are infected with the influenza virus may develop respiratory illnesses, such as pneumonia, or other life-threatening complications. Currently, there are four antiviral medications that are used to treat influenza. This study will examine one of these medications, oseltamivir, to examine how it affects the shedding of influenza virus in infected people.
Detailed Description
Seasonal influenza is responsible for excess hospitalizations and, despite effective antivirals, causes significant morbidity and mortality (about 24,000 deaths each year in the United States alone). The influenza virus that emerged in 2009 (A/California/07/2009 H1N1) caused fewer deaths (12,000 flu-related deaths in the U.S.) but in contrast to seasonal flu, nearly 90% of the deaths with the 2009 H1N1 occurred among people younger than 65 years of age. Although there are four currently licensed anti-influenza medications (amantadine and rimantadine, oseltamivir, and zanamivir), previous studies have not demonstrated conclusively to what extent these medications affect influenza viral shedding. This study will evaluate whether oseltamivir modifies the viral shedding during the treatment of uncomplicated influenza in an adult population and also assess methods to detect viral replication in the upper respiratory tract.
Subjects who presented with an influenza-like illness without any risk factors for severe disease were screened for the study. Those with a confirmatory test for influenza (rapid antigen or polymerase chain reaction [PCR]) were randomized in a 1:1 manner to receive a blinded study treatment consisting of either the oseltamivir or placebo for 5 days. Clinical, virologic, and laboratory assessments on Days 1, 3, 7, and 28 were used for both safety and efficacy analysis.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 64 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Written informed consent prior to initiation of any study procedures
- •History of an influenza-like illness defined as:
- •One or more respiratory symptom (cough, sore throat, or nasal symptoms)
- •Onset of illness no more than 48 hours before screening, defined as when the participant experienced at least one respiratory symptom
- •Willing to have samples stored
- •Positive test for influenza (either rapid antigen or polymerase chain reaction \[PCR\]); randomization could proceed in cases of discrepant results (one positive and one negative)
Exclusion Criteria
- •Hospitalization at the time of screening
- •Presence of a medical condition(s) that had been associated with increased risk of complications from influenza
- •Aged 65 years of age or older
- •Neurological and neuro-developmental conditions (including disorders of the brain, spinal cord, peripheral nerve, and muscle, such as cerebral palsy, epilepsy \[seizure disorders\], stroke, moderate to severe developmental delay, muscular dystrophy, or spinal cord injury)
- •Chronic lung disease (such as chronic obstructive pulmonary disease \[COPD\] or cystic fibrosis)
- •Heart disease (such as congenital heart disease, congestive heart failure, or coronary artery disease)
- •Blood disorders
- •Endocrine disorders (such as diabetes mellitus)
- •Kidney disorders
- •Liver disorders
Arms & Interventions
Oseltamivir
Intervention: Oseltamivir (Drug)
Placebo
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Percentage of Participants With Virus Detectable by Quantitative PCR (qPCR) in Nasopharyngeal (NP) Swabs at Day 3 -- Team Collected Samples
Time Frame: At Day 3
The central laboratory performed a qualitative PCR test on the NP sample from Day 0 team collected swap 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 Outcomes
- 28-day Mortality(From treatment initiation to Day 28)
- Number of Participants by Virus Detection Status--Team Collected Samples(At Day 0, 3 and 7)
- Time to Resolution of All Symptoms AND Fever(From treatment initiation to Day 28)
- qPCR Viral Shedding -- Team Collected Samples(At Day 0, 3 and 7)
- Number Of Participants Shedding Virus -- Team Collected Samples(At day 3 and 7.)
- Time to Return of Physical Function to Pre-illness Level(From treatment initiation to Day 28)
- Time to Alleviation of Influenza Clinical Symptoms(From treatment initiation to Day 28)
- Time to Absence of Fever(From treatment initiation to Day 28)
- Time to Return to Pre-influenza Function(From treatment initiation to Day 28)
- Number of Participants With Treatment Compliance Status(From treatment initiation to Day 5)
- Percentage of Participants Who Develop Bronchitis, Pneumonia, or Other Complications Requiring An Antibiotic Use, After Day 0.(From treatment initiation to Day 28)
- Percentage of Participants With Virus Detectable by Quantitative PCR (qPCR) in Nasopharyngeal (NP) Swabs --Self Collected Samples(At Day 3)
- Time to Feeling as Good as Before the Onset of the Influenza Illness(From treatment initiation to Day 28)
- Number of Participants by Virus Detection Status --Self Collected Samples(At Day 0, Day 0 evening, Day 1, Day 1 evening, Day 2, Day 2 evening and Day 3)
- Percentage of Participants Who Required Hospitalization.(From treatment initiation to Day 28)
- qPCR Viral Shedding -- Self Collected Samples(At Day 0, Day 0 evening, Day 1, Day 1 evening, Day 2, Day 2 evening and Day 3)
- Area Under The Curve (AUC) Of Viral Shedding For Self Collected Samples(From Day 0 to Day 3)