Clinical trial NCT01314911: Evaluating the Use of Oseltamivir for the Treatment of Influenza in Adults
Official title: A Randomized Double-Blind Study Comparing Oseltamivir Versus Placebo for the Treatment of Influenza in Low Risk Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Influenza, Human
Keywords: H1N1
Complications
PCR
Seasonal Influenza
Viral Shedding
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2011-03-15
Enrollment: 716
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Percentage of Participants With Virus Detectable by Quantitative PCR (qPCR) in Nasopharyngeal (NP) Swabs at Day 3 -- Team Collected Samples
timeFrame: At Day 3
Secondary outcomes:
measure: Number of Participants by Virus Detection Status--Team Collected Samples
timeFrame: At Day 0, 3 and 7
measure: qPCR Viral Shedding -- Team Collected Samples
timeFrame: At Day 0, 3 and 7
measure: Number Of Participants Shedding Virus -- Team Collected Samples
timeFrame: At day 3 and 7.
measure: Time to Alleviation of Influenza Clinical Symptoms
timeFrame: From treatment initiation to Day 28
measure: Time to Absence of Fever
timeFrame: From treatment initiation to Day 28
measure: Time to Resolution of All Symptoms AND Fever
timeFrame: From treatment initiation to Day 28
measure: Time to Feeling as Good as Before the Onset of the Influenza Illness
timeFrame: From treatment initiation to Day 28
measure: Time to Return to Pre-influenza Function
timeFrame: From treatment initiation to Day 28
measure: Time to Return of Physical Function to Pre-illness Level
timeFrame: From treatment initiation to Day 28
measure: Number of Participants With Treatment Compliance Status
timeFrame: From treatment initiation to Day 5
measure: Percentage of Participants Who Required Hospitalization.
timeFrame: From treatment initiation to Day 28
measure: Percentage of Participants Who Develop Bronchitis, Pneumonia, or Other Complications Requiring An Antibiotic Use, After Day 0.
timeFrame: From treatment initiation to Day 28
measure: 28-day Mortality
timeFrame: From treatment initiation to Day 28
measure: Percentage of Participants With Virus Detectable by Quantitative PCR (qPCR) in Nasopharyngeal (NP) Swabs --Self Collected Samples
timeFrame: At Day 3
measure: Number of Participants by Virus Detection Status --Self Collected Samples
timeFrame: At Day 0, Day 0 evening, Day 1, Day 1 evening, Day 2, Day 2 evening and Day 3
measure: qPCR Viral Shedding -- Self Collected Samples
timeFrame: At Day 0, Day 0 evening, Day 1, Day 1 evening, Day 2, Day 2 evening and Day 3
measure: Area Under The Curve (AUC) Of Viral Shedding For Self Collected Samples
timeFrame: From Day 0 to Day 3
Other outcomes:
Locations:
city: Chandler
country: United States
facility: East Valley Family Physicians
state: Arizona
city: Costa Mesa
country: United States
facility: WCCT Global, LLC
state: California
city: Garden Grove
country: United States
facility: Paragon Rx Clinical
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: San Diego
country: United States
facility: University of California, San Diego
state: California
city: Thousand Oaks
country: United States
facility: Westlake Medical Research
state: California
city: Westminster
country: United States
facility: Advanced Rx Clinical Research Group
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Hialeah
country: United States
facility: Best Quality Research, Inc.
state: Florida
city: Miami
country: United States
facility: Medical Consulting Center
state: Florida
city: Miami
country: United States
facility: Suncoast Research Group, LLC
state: Florida
city: Pinellas Park
country: United States
facility: DMI Research, Inc.
state: Florida
city: Columbus
country: United States
facility: Columbus Regional Research Institute
state: Georgia
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Owensboro
country: United States
facility: Research Integrity, LLC
state: Kentucky
city: Eunice
country: United States
facility: Horizon Research Group of Opelousas, LLC
state: Louisiana
city: Lake Charles
country: United States
facility: Michael Seep, MD; Centex Studies
state: Louisiana
city: Bethesda
country: United States
facility: National Institutes of Health, Laboratory of Immunoregulation
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Elkhorn
country: United States
facility: Skyline Medical Center
state: Nebraska
city: Fremont
country: United States
facility: Prairie Fields Family Medicine
state: Nebraska
city: Omaha
country: United States
facility: Southwest Family Physicians
state: Nebraska
city: Omaha
country: United States
facility: Clinical Research Advantage, Inc.
state: Nebraska
city: Newark
country: United States
facility: New Jersey Medical School
state: New Jersey
city: New York
country: United States
facility: NYU School of Medicine
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Westfield
country: United States
facility: Great Lakes Medical Research
state: New York
city: Middleburg Heights
country: United States
facility: Clinical Research Solutions
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania, Division of Infectious Disease
state: Pennsylvania
city: Smithfield
country: United States
facility: Frontier Clinical Research, LLC
state: Pennsylvania
city: Rapid City
country: United States
facility: Health Concepts
state: South Dakota
city: Franklin
country: United States
facility: Clinical Research Solutions
state: Tennessee
city: Jackson
country: United States
facility: Clinical Research Solutions
state: Tennessee
city: Nashville
country: United States
facility: Clinical Research Solutions
state: Tennessee
city: Smyrna
country: United States
facility: Clinical Research Solutions
state: Tennessee
city: Amarillo
country: United States
facility: University of Texas Tech Amarillo
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston
state: Texas
city: Houston
country: United States
facility: Centex Studies
state: Texas
city: Lubbock
country: United States
facility: Texas Tech University Health Sciences Center
state: Texas
city: Plano
country: United States
facility: Village Health Partners
state: Texas
city: San Antonio
country: United States
facility: Bandera Family Health Care
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University Medical Center
state: Virginia
city: Buenos Aires
country: Argentina
facility: Hospital General de Agudos J. M. Ramos Mejía
city: Buenos Aires
country: Argentina
facility: Hospital Municipal "Prof. Dr. Bernardo A. Houssay"
city: Cordoba
country: Argentina
facility: Hospital Público Descentralizado Dr. Guillermo Rawson
city: Mueang Nonthaburi
country: Thailand
facility: The Bamrasnaradura Infectious Diseases Institute
state: Nonthaburi
city: Bangkok
country: Thailand
facility: The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)
city: Bangkok
country: Thailand
facility: Siriraj Hospital
city: Khon Kaen
country: Thailand
facility: Khon Kaen University (Department of Medicine)
Study officials:
affiliation: Leidos Biomedical Research, Inc. in support of Clinical Research Section, LIR, NIAID, National Institutes of Health
name: John Beigel, MD
role: STUDY_CHAIR
affiliation: Division of Infectious Disease, Feinberg School of Medicine, Northwestern University
name: Michael Ison, MD, MS
role: STUDY_CHAIR
References:
citation: 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.
citation: Monto AS. Vaccines and antiviral drugs in pandemic preparedness. Emerg Infect Dis. 2006 Jan;12(1):55-60. doi: 10.3201/eid1201.051068.
citation: 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.