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

NCT ID: NCT01314911

Last Updated: 2019-02-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 716 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-04-30
• Study Completion Date: 2017-11-18

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.

Conditions

Influenza, Human

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Oseltamivir

Group Type: EXPERIMENTAL

Oseltamivir

Intervention Type: DRUG

Subjects were prescribed Oseltamivir twice daily for 5 days, and each dose consisted of one capsule of Oseltamivir 75 mg.

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Subjects were prescribed the matching placebo twice daily for 5 days, and each dose consisted of one capsule of placebo.

Interventions

Oseltamivir

Subjects were prescribed Oseltamivir twice daily for 5 days, and each dose consisted of one capsule of Oseltamivir 75 mg.

Intervention Type: DRUG

Placebo

Subjects were prescribed the matching placebo twice daily for 5 days, and each dose consisted of one capsule of placebo.

Intervention Type: DRUG

Eligibility 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 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John Beigel, MD

Role: STUDY_CHAIR

Leidos Biomedical Research, Inc. in support of Clinical Research Section, LIR, NIAID, National Institutes of Health

Michael Ison, MD, MS

Role: STUDY_CHAIR

Division of Infectious Disease, Feinberg School of Medicine, Northwestern University

Locations

East Valley Family Physicians

Chandler, Arizona, United States

WCCT Global, LLC

Costa Mesa, California, United States

Paragon Rx Clinical

Garden Grove, California, United States

University of Southern California

Los Angeles, California, United States

University of California, San Diego

San Diego, California, United States

Westlake Medical Research

Thousand Oaks, California, United States

Advanced Rx Clinical Research Group

Westminster, California, United States

University of Colorado

Aurora, Colorado, United States

University of Florida

Gainesville, Florida, United States

Best Quality Research, Inc.

Hialeah, Florida, United States

Medical Consulting Center

Miami, Florida, United States

Suncoast Research Group, LLC

Miami, Florida, United States

DMI Research, Inc.

Pinellas Park, Florida, United States

Columbus Regional Research Institute

Columbus, Georgia, United States

University of Iowa

Iowa City, Iowa, United States

Research Integrity, LLC

Owensboro, Kentucky, United States

Horizon Research Group of Opelousas, LLC

Eunice, Louisiana, United States

Michael Seep, MD; Centex Studies

Lake Charles, Louisiana, United States

National Institutes of Health, Laboratory of Immunoregulation

Bethesda, Maryland, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

Skyline Medical Center

Elkhorn, Nebraska, United States

Prairie Fields Family Medicine

Fremont, Nebraska, United States

Southwest Family Physicians

Omaha, Nebraska, United States

Clinical Research Advantage, Inc.

Omaha, Nebraska, United States

New Jersey Medical School

Newark, New Jersey, United States

NYU School of Medicine

New York, New York, United States

Mount Sinai Medical Center

New York, New York, United States

University of Rochester Medical Center

Rochester, New York, United States

Great Lakes Medical Research

Westfield, New York, United States

Clinical Research Solutions

Middleburg Heights, Ohio, United States

University of Pennsylvania, Division of Infectious Disease

Philadelphia, Pennsylvania, United States

Frontier Clinical Research, LLC

Smithfield, Pennsylvania, United States

Health Concepts

Rapid City, South Dakota, United States

Clinical Research Solutions

Franklin, Tennessee, United States

Clinical Research Solutions

Jackson, Tennessee, United States

Clinical Research Solutions

Nashville, Tennessee, United States

Clinical Research Solutions

Smyrna, Tennessee, United States

University of Texas Tech Amarillo

Amarillo, Texas, United States

University of Texas Health Science Center at Houston

Houston, Texas, United States

Centex Studies

Houston, Texas, United States

Texas Tech University Health Sciences Center

Lubbock, Texas, United States

Village Health Partners

Plano, Texas, United States

Bandera Family Health Care

San Antonio, Texas, United States

Virginia Commonwealth University Medical Center

Richmond, Virginia, United States

Hospital General de Agudos J. M. Ramos Mejía

Buenos Aires, , Argentina

Hospital Municipal "Prof. Dr. Bernardo A. Houssay"

Buenos Aires, , Argentina

Hospital Público Descentralizado Dr. Guillermo Rawson

Córdoba, , Argentina

The Bamrasnaradura Infectious Diseases Institute

Nonthaburi, Changwat Nonthaburi, Thailand

The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)

Bangkok, , Thailand

Siriraj Hospital

Bangkok, , Thailand

Khon Kaen University (Department of Medicine)

Khon Kaen, , Thailand

Countries

United States; Argentina; Thailand

References

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. doi: 10.1001/jama.289.2.179.

Reference Type: BACKGROUND

PMID: 12517228 (View on PubMed)

Monto AS. Vaccines and antiviral drugs in pandemic preparedness. Emerg Infect Dis. 2006 Jan;12(1):55-60. doi: 10.3201/eid1201.051068.

Reference Type: BACKGROUND

PMID: 16494718 (View on PubMed)

Beigel JH, Manosuthi W, Beeler J, Bao Y, Hoppers M, Ruxrungtham K, Beasley RL, Ison M, Avihingsanon A, Losso MH, Langlois N, Hoopes J, Lane HC, Holley HP, Myers CA, Hughes MD, Davey RT. Effect of Oral Oseltamivir on Virological Outcomes in Low-risk Adults With Influenza: A Randomized Clinical Trial. Clin Infect Dis. 2020 May 23;70(11):2317-2324. doi: 10.1093/cid/ciz634.

Reference Type: DERIVED

PMID: 31541242 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Related Links

https://rsc.niaid.nih.gov/clinical-research-sites/daids-adverse-event-grading-tables

The DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004 (Clarification, August 2009).

Other Identifiers

11-I-0031

Identifier Type: -

Identifier Source: secondary_id

IRC004

Identifier Type: -

Identifier Source: secondary_id

IRC 004

Identifier Type: -

Identifier Source: org_study_id