Evaluating the Use of Oseltamivir for the Treatment of Influenza in Adults

National Institute of Allergy and Infectious Diseases (NIAID)

Status

Completed

Conditions

Influenza, Human

Treatments

Drug: Placebo

Drug: Oseltamivir

Study type

Interventional

Funder types

NIH

Identifiers

NCT01314911

IRC004

11-I-0031

IRC 004

Details and patient eligibility

About

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.

Full 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.

Enrollment

716 patients

Sex

All

Ages

18 to 64 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Written informed consent prior to initiation of any study procedures
History of an influenza-like illness defined as:
1. 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
1. Aged 65 years of age or older
2. Asthma
3. 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)
4. Chronic lung disease (such as chronic obstructive pulmonary disease [COPD] or cystic fibrosis)
5. Heart disease (such as congenital heart disease, congestive heart failure, or coronary artery disease)
6. Blood disorders
7. Endocrine disorders (such as diabetes mellitus)
8. Kidney disorders
9. Liver disorders
10. Metabolic disorders (such as inherited metabolic disorders or mitochondrial disorders)
11. Weakened immune system due to disease or medication (such as people with HIV/AIDS or cancer, or use of chronic steroids or other medications causing immune suppression)
12. Pregnant or 4 weeks postpartum
13. Body mass index (BMI) greater than or equal to 40
Breastfeeding
Inability to take oral medication or a history of gastrointestinal malabsorption that would preclude the use of oral medication
Received more than one dose of any antiviral influenza medication since onset of influenza symptoms
Known end stage kidney dysfunction (e.g., creatinine clearance less than 30 mL/min)
Known hypersensitivity to oseltamivir, peramivir, or zanamivir
Received live attenuated influenza virus vaccine within 3 weeks prior to study entry
Use of any investigational drug within 30 days or 5 half-lives (whichever was longer) prior to study entry
Participated in other research protocols that required more than 100mL of blood to be drawn in a 4-week period that overlapped with this study.