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

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Influenza, Human	Drug: Oseltamivir; Drug: Oseltamivir Placebo	Not Applicable

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 present with an influenza-like illness without any risk factors for severe disease will be screened for the study. Those with a confirmatory test for influenza (rapid antigen or polymerase chain reaction [PCR]) will be 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 will be used for both safety and efficacy analysis.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	800 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Investigator)
Primary Purpose:	Treatment
Official Title:	A Randomized Double-Blind Study Comparing Oseltamivir Versus Placebo for the Treatment of Influenza in Low Risk Adults
Study Start Date :	April 2011
Estimated Primary Completion Date :	June 2019

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Oseltamivir; Participants will receive oseltamivir twice a day for 5 days.	Drug: Oseltamivir; One capsule twice daily of 75 mg oseltamivir; total dose: 150 mg/day for 5 days
Placebo Comparator: Oseltamivir Placebo; Participants will receive oseltamivir placebo twice a day for 5 days.	Drug: Oseltamivir Placebo; One capsule twice daily of oseltamivir placebo; total dose: 2 placebo capsules/day for 5 days

Outcome Measures

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Primary Outcome Measures :

1. Primary Endpoint is the percentage of subjects shedding virus by PCR in NP swab at day 3. [ Time Frame: Measured at Day 3 ]

Secondary Outcome Measures :

1. Time to alleviation of influenza clinical symptoms [ Time Frame: Measured at Day 28 ]
2. Time to absence of fever [ Time Frame: Measured at Day 28 ]
3. Time to resumption of normal activity [ Time Frame: Measured at Day 28 ]
4. Number of premature study treatment discontinuations [ Time Frame: Measured at Day 28 ]
5. Proportion of participants who develop bronchitis, pneumonia, or other complications of influenza [ Time Frame: Measured at Day 28 ]
6. Proportion of participants who require hospitalization [ Time Frame: Measured at Day 28 ]
7. 28-day mortality [ Time Frame: Measured at Day 28 ]
8. Duration of viral shedding [ Time Frame: Measured at Day 28 ]
9. Change in viral shedding as a function of time [ Time Frame: Measured at Day 28 ]
10. Area under the curve (AUC) of viral shedding [ Time Frame: Measured at Day 28 ]
11. Frequency of emergence of antiviral resistance [ Time Frame: Measured at Day 28 ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 64 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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 may 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 has been associated with increased risk of complications from influenza

  1. Age 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 is longer) prior to study entry
• Participation in other research protocols that require more than 100mL of blood to be drawn in a 4-week period that overlaps with this study.

Contacts and Locations

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Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Study Chair:	John Beigel, MD	Leidos Biomedical Research, Inc. in support of Clinical Research Section, LIR, NIAID, National Institutes of Health
Study Chair:	Michael Ison, MD, MS	Division of Infectious Disease, Feinberg School of Medicine, Northwestern University

More Information

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Publications:

Thompson WW, Shay DK, Weintraub E, Brammer L, Cox N, Anderson LJ, Fukuda K. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA. 2003 Jan 8;289(2):179-86.

Monto AS. Vaccines and antiviral drugs in pandemic preparedness. Emerg Infect Dis. 2006 Jan;12(1):55-60.

Responsible Party:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT01314911 History of Changes
Other Study ID Numbers:	IRC 004; 11-I-0031; IRC004
First Posted:	March 15, 2011
Last Update Posted:	November 20, 2017
Last Verified:	November 2017

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

H1N1; Complications; PCR; Seasonal Influenza; Viral Shedding

Additional relevant MeSH terms:

Influenza, Human; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases	Oseltamivir; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action