Back to resultsA Study of Tamiflu (Oseltamivir) for Treatment of Influenza With a Focus on (H1N1) 2009 Flu Strain
Primary Purpose
Influenza
Status
Terminated
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Oseltamivir
Oseltamivir
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Influenza
Eligibility Criteria
Inclusion Criteria:
- Pediatric, adolescent and adult patients >/=1 year of age
- Fever >/=37.8 degrees C or at least one respiratory symptom (cough, coryza, sore throat, or rhinitis)
- Positive rapid diagnostic test for pandemic (H1N1) 2009 virus or influenza A in the 24 hours prior to the first dose of study drug
- </=96 hours between onset of influenza-like illness and first dose of oseltamivir
Exclusion Criteria:
- Currently receiving any form of renal replacement therapy including hemodialysis, peritoneal dialysis, or hemofiltration
- History of chronic renal failure or clinical suspicion of renal failure at baseline
- Clinical evidence of hepatic compensation at the time of randomization
- Known HIV infection
- Vaccination with live attenuated influenza vaccine (LAIV) in the two weeks prior to first dose of study medication
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Oseltamivir standard dose 5 days
Oseltamivir standard dose 10 days
Oseltamivir high dose 5 days
Oseltamivir high dose 10 days
Arm Description
Adults and children 13 years and older received 75 mg oseltamivir and a placebo capsule twice daily for 5 days. Children aged 1 - 12 years received a weight-based dose (from 30 to 75 mg) oseltamivir suspension and placebo suspension orally twice daily for 5 days. Participants received matching placebo for the second 5 days of treatment.
Adults and children 13 years and older received 75 mg oseltamivir and a placebo capsule twice daily for 10 days. Children aged 1 - 12 years received a weight-based dose (from 30 to 75 mg) oseltamivir suspension and placebo suspension orally twice daily for 10 days.
Adults and children 13 years and older received 150 mg (2 x 75 mg) oseltamivir capsules twice daily for 5 days. Children aged 1 - 12 years received a weight-based dose (from 60 to 150 mg) oseltamivir suspension orally twice daily for 5 days. Participants received matching placebo for the second 5 days of treatment.
Adults and children 13 years and older received 150 mg (2 x 75 mg) oseltamivir capsules twice daily for 10 days. Children aged 1- 12 years received a weight-based dose (from 60 to 150 mg) oseltamivir suspension orally twice daily for 10 days.
Outcomes
Primary Outcome Measures
Time to Cessation of Viral Shedding
The time to cessation of viral shedding was measured by viral culture and defined as the time from treatment initiation to the time of the first negative culture with no subsequent positive cultures. Any patient with a positive culture at the last sample time was censored at that time point. Median time to cessation was estimated from the Kaplan-Meier curve.
Secondary Outcome Measures
Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Viral Culture
Viral shedding was measured by viral culture from samples obtained from nasal and throat swabs and performed by the central laboratory.
Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Reverse Transcriptase Polymerase Chain Reaction
Viral shedding was measured by reverse transcriptase polymerase chain reaction (RT-PCR) from samples obtained from nasal and throat swabs and performed by the central laboratory.
Change From Baseline in Influenza Titer Measured by Viral Culture
Influenza virus titer measured by viral culture and expressed on a Log10 scale of the 50% Tissue Culture Infective Dose (TCID50; amount of virus required to kill 50% of inoculated tissue culture cells).
Number of Participants With Development of Oseltamivir-Resistant Influenza Virus
The last positive viral isolate from each patient was tested for reduced sensitivity to oseltamivir. Phenotypic assay was performed to determine the susceptibility of the last positive viral isolate from each patient. If required, a genotypic assay to determine the contribution of both the neuraminidase (NA) and hemagglutinin (HA) genes to decreased susceptibility was also performed.
Time to Resolution of Fever
Temperature was recorded by the patient in a diary twice daily for 10 days and once daily thereafter. Fever was defined as a body temperature greater than or including 37.8 degrees Celsius (or ≥ 100.04 Fahrenheit). Time to resolution of fever was defined as the total number of hours from the first dose of study medication to the first time at which temperature is ≤ 37.2 degrees Celsius and lasts at least 21.5 hours. Patients who were still febrile at the end of the study period were censored at that time.
Time to Alleviation of All Clinical Symptoms - Children
Daily influenza-like symptoms (such as poor appetite, irritability, low energy, nasal congestion, runny nose etc) were recorded in a diary on a scale from 0 (no problem) to 3 (major problem). A patient is considered free of all clinical influenza symptoms if all symptoms were checked as 'no problem' or 'minor problem' (i.e., symptom score ≤1). Time to alleviation of all clinical symptoms was defined as the number of hours from the first dose to the first time the patient had alleviation of all symptoms. Patients without alleviation of symptoms were censored at the last available assessment.
Time to Alleviation of All Clinical Symptoms - Adults
Daily influenza-like symptoms (such as nasal congestion, sore throat, cough, aches and pains, fatigue, headache, chills) were recorded in a diary on a scale from 0 (absent) to 3 (severe). A patient is considered free of all clinical influenza symptoms if all symptoms were checked as 'absent' or 'mild' (i.e., symptom score ≤1). Time to alleviation of all clinical symptoms was defined as the number of hours from the first dose to the first time the patient had alleviation of all symptoms. Patients without alleviation of symptoms were censored at the last available assessment.
Number of Participants Who Developed Secondary Illnesses During the Study
The number of participants who developed secondary illnesses due to influenza, including four pre-defined adverse events: otitis media, bronchitis, pneumonia, or sinusitis at any time during the study.
Number of Participants Who Developed Secondary Illnesses That Were Treated With Antibiotics
The number of participants who developed secondary illnesses due to influenza, including otitis media, bronchitis, pneumonia, or sinusitis at any time during the study which were treated with antibiotics.
Full Information
NCT ID
NCT01032837
First Posted
December 10, 2009
Last Updated
September 18, 2012
Sponsor
Hoffmann-La Roche
1. Study Identification
Unique Protocol Identification Number
NCT01032837
Brief Title
A Study of Tamiflu (Oseltamivir) for Treatment of Influenza With a Focus on (H1N1) 2009 Flu Strain
Official Title
A Randomized, Multicenter Trial of Oseltamivir [Tamiflu] Doses of 75 mg for 5 or 10 Days Versus 150 mg for 5 or 10 Days to Evaluate the Effect on the Duration of Viral Shedding in Influenza Patients With Pandemic (H1N1) 2009
Study Type
Interventional
2. Study Status
Record Verification Date
September 2012
Overall Recruitment Status
Terminated
Why Stopped
Study closed prematurely due to the end of the influenza (H1N1) 2009 pandemic
Study Start Date
November 2009 (undefined)
Primary Completion Date
October 2010 (Actual)
Study Completion Date
October 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
5. Study Description
Brief Summary
This randomized, double-blind, multi-center study of Tamiflu (Oseltamivir) will evaluate the efficacy against viral activity, the effectiveness in resolving the disease symptoms, and the safety and tolerability in patients with influenza. Patients with (H1N1) 2009 influenza strain or influenza A are eligible for this study. Patients will be randomized to one of four treatment regimens. Patients will receive oral doses of either 75 mg (adults) or 150 mg (adults) of study drug twice daily for 5 or 10 consecutive days. The dose will be body weight-adjusted for pediatric patients.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Influenza
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
102 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Oseltamivir standard dose 5 days
Arm Type
Experimental
Arm Description
Adults and children 13 years and older received 75 mg oseltamivir and a placebo capsule twice daily for 5 days. Children aged 1 - 12 years received a weight-based dose (from 30 to 75 mg) oseltamivir suspension and placebo suspension orally twice daily for 5 days. Participants received matching placebo for the second 5 days of treatment.
Arm Title
Oseltamivir standard dose 10 days
Arm Type
Experimental
Arm Description
Adults and children 13 years and older received 75 mg oseltamivir and a placebo capsule twice daily for 10 days. Children aged 1 - 12 years received a weight-based dose (from 30 to 75 mg) oseltamivir suspension and placebo suspension orally twice daily for 10 days.
Arm Title
Oseltamivir high dose 5 days
Arm Type
Experimental
Arm Description
Adults and children 13 years and older received 150 mg (2 x 75 mg) oseltamivir capsules twice daily for 5 days. Children aged 1 - 12 years received a weight-based dose (from 60 to 150 mg) oseltamivir suspension orally twice daily for 5 days. Participants received matching placebo for the second 5 days of treatment.
Arm Title
Oseltamivir high dose 10 days
Arm Type
Experimental
Arm Description
Adults and children 13 years and older received 150 mg (2 x 75 mg) oseltamivir capsules twice daily for 10 days. Children aged 1- 12 years received a weight-based dose (from 60 to 150 mg) oseltamivir suspension orally twice daily for 10 days.
Intervention Type
Drug
Intervention Name(s)
Oseltamivir
Other Intervention Name(s)
Tamiflu
Intervention Description
Oseltamivir capsules for participants ≥ 13 years.
Intervention Type
Drug
Intervention Name(s)
Oseltamivir
Other Intervention Name(s)
Tamiflu
Intervention Description
Pediatric suspension for participants aged ≤ 12 years.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo provided as capsules and as a suspension.
Primary Outcome Measure Information:
Title
Time to Cessation of Viral Shedding
Description
The time to cessation of viral shedding was measured by viral culture and defined as the time from treatment initiation to the time of the first negative culture with no subsequent positive cultures. Any patient with a positive culture at the last sample time was censored at that time point. Median time to cessation was estimated from the Kaplan-Meier curve.
Time Frame
Day 1 to Day 40
Secondary Outcome Measure Information:
Title
Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Viral Culture
Description
Viral shedding was measured by viral culture from samples obtained from nasal and throat swabs and performed by the central laboratory.
Time Frame
Baseline and Days 3, 6, 8, 11, 15 and 40
Title
Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Reverse Transcriptase Polymerase Chain Reaction
Description
Viral shedding was measured by reverse transcriptase polymerase chain reaction (RT-PCR) from samples obtained from nasal and throat swabs and performed by the central laboratory.
Time Frame
Baseline and Days 3, 6, 8, 11, 15 and 40
Title
Change From Baseline in Influenza Titer Measured by Viral Culture
Description
Influenza virus titer measured by viral culture and expressed on a Log10 scale of the 50% Tissue Culture Infective Dose (TCID50; amount of virus required to kill 50% of inoculated tissue culture cells).
Time Frame
Baseline, Days 2 through 15
Title
Number of Participants With Development of Oseltamivir-Resistant Influenza Virus
Description
The last positive viral isolate from each patient was tested for reduced sensitivity to oseltamivir. Phenotypic assay was performed to determine the susceptibility of the last positive viral isolate from each patient. If required, a genotypic assay to determine the contribution of both the neuraminidase (NA) and hemagglutinin (HA) genes to decreased susceptibility was also performed.
Time Frame
40 days
Title
Time to Resolution of Fever
Description
Temperature was recorded by the patient in a diary twice daily for 10 days and once daily thereafter. Fever was defined as a body temperature greater than or including 37.8 degrees Celsius (or ≥ 100.04 Fahrenheit). Time to resolution of fever was defined as the total number of hours from the first dose of study medication to the first time at which temperature is ≤ 37.2 degrees Celsius and lasts at least 21.5 hours. Patients who were still febrile at the end of the study period were censored at that time.
Time Frame
Day 1 through Day 40
Title
Time to Alleviation of All Clinical Symptoms - Children
Description
Daily influenza-like symptoms (such as poor appetite, irritability, low energy, nasal congestion, runny nose etc) were recorded in a diary on a scale from 0 (no problem) to 3 (major problem). A patient is considered free of all clinical influenza symptoms if all symptoms were checked as 'no problem' or 'minor problem' (i.e., symptom score ≤1). Time to alleviation of all clinical symptoms was defined as the number of hours from the first dose to the first time the patient had alleviation of all symptoms. Patients without alleviation of symptoms were censored at the last available assessment.
Time Frame
Day 1 to Day 40
Title
Time to Alleviation of All Clinical Symptoms - Adults
Description
Daily influenza-like symptoms (such as nasal congestion, sore throat, cough, aches and pains, fatigue, headache, chills) were recorded in a diary on a scale from 0 (absent) to 3 (severe). A patient is considered free of all clinical influenza symptoms if all symptoms were checked as 'absent' or 'mild' (i.e., symptom score ≤1). Time to alleviation of all clinical symptoms was defined as the number of hours from the first dose to the first time the patient had alleviation of all symptoms. Patients without alleviation of symptoms were censored at the last available assessment.
Time Frame
Day 1 to Day 40
Title
Number of Participants Who Developed Secondary Illnesses During the Study
Description
The number of participants who developed secondary illnesses due to influenza, including four pre-defined adverse events: otitis media, bronchitis, pneumonia, or sinusitis at any time during the study.
Time Frame
Day 1 through Day 40
Title
Number of Participants Who Developed Secondary Illnesses That Were Treated With Antibiotics
Description
The number of participants who developed secondary illnesses due to influenza, including otitis media, bronchitis, pneumonia, or sinusitis at any time during the study which were treated with antibiotics.
Time Frame
Day 1 through Day 40
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Pediatric, adolescent and adult patients >/=1 year of age
Fever >/=37.8 degrees C or at least one respiratory symptom (cough, coryza, sore throat, or rhinitis)
Positive rapid diagnostic test for pandemic (H1N1) 2009 virus or influenza A in the 24 hours prior to the first dose of study drug
</=96 hours between onset of influenza-like illness and first dose of oseltamivir
Exclusion Criteria:
Currently receiving any form of renal replacement therapy including hemodialysis, peritoneal dialysis, or hemofiltration
History of chronic renal failure or clinical suspicion of renal failure at baseline
Clinical evidence of hepatic compensation at the time of randomization
Known HIV infection
Vaccination with live attenuated influenza vaccine (LAIV) in the two weeks prior to first dose of study medication
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
City
Tuscaloosa
State/Province
Alabama
ZIP/Postal Code
35406
Country
United States
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85016
Country
United States
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85050
Country
United States
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85248
Country
United States
City
Jonesboro
State/Province
Arkansas
ZIP/Postal Code
72401
Country
United States
City
Carmichael
State/Province
California
ZIP/Postal Code
95608
Country
United States
City
Downey
State/Province
California
ZIP/Postal Code
90241
Country
United States
City
Fountain Valley
State/Province
California
ZIP/Postal Code
92708
Country
United States
City
Huntington Beach
State/Province
California
ZIP/Postal Code
92647
Country
United States
City
Lomita
State/Province
California
ZIP/Postal Code
90717
Country
United States
City
National City
State/Province
California
ZIP/Postal Code
91950
Country
United States
City
Paramount
State/Province
California
ZIP/Postal Code
90723
Country
United States
City
Sacramento
State/Province
California
ZIP/Postal Code
95823
Country
United States
City
San Diego
State/Province
California
ZIP/Postal Code
92103-6204
Country
United States
City
San Diego
State/Province
California
ZIP/Postal Code
92120
Country
United States
City
Colorado Springs
State/Province
Colorado
ZIP/Postal Code
80909
Country
United States
City
Deland
State/Province
Florida
ZIP/Postal Code
32720
Country
United States
City
Fleming Island
State/Province
Florida
ZIP/Postal Code
32003
Country
United States
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32607
Country
United States
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32205
Country
United States
City
Largo
State/Province
Florida
ZIP/Postal Code
33770
Country
United States
City
Miami
State/Province
Florida
ZIP/Postal Code
33126
Country
United States
City
Miami
State/Province
Florida
ZIP/Postal Code
33135
Country
United States
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
City
Pembroke Pines
State/Province
Florida
ZIP/Postal Code
33026
Country
United States
City
St. Cloud
State/Province
Florida
ZIP/Postal Code
34769
Country
United States
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
City
Idaho Falls
State/Province
Idaho
ZIP/Postal Code
83404
Country
United States
City
Meridian
State/Province
Idaho
ZIP/Postal Code
83642
Country
United States
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60622
Country
United States
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46268
Country
United States
City
Newburgh
State/Province
Indiana
ZIP/Postal Code
47630
Country
United States
City
Dubuque
State/Province
Iowa
ZIP/Postal Code
52002
Country
United States
City
Overland Park
State/Province
Kansas
ZIP/Postal Code
66210
Country
United States
City
Bardstown
State/Province
Kentucky
ZIP/Postal Code
40004
Country
United States
City
Madisonville
State/Province
Kentucky
ZIP/Postal Code
42431
Country
United States
City
Lake Charles
State/Province
Louisiana
ZIP/Postal Code
70601
Country
United States
City
Mandeville
State/Province
Louisiana
ZIP/Postal Code
70471
Country
United States
City
Meltairie
State/Province
Louisiana
ZIP/Postal Code
70006
Country
United States
City
Shreveprt
State/Province
Louisiana
ZIP/Postal Code
71106
Country
United States
City
Brockton
State/Province
Massachusetts
ZIP/Postal Code
02301
Country
United States
City
Stevensville
State/Province
Michigan
ZIP/Postal Code
49127
Country
United States
City
Bridgeton
State/Province
Missouri
ZIP/Postal Code
63044
Country
United States
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63141
Country
United States
City
Bozeman
State/Province
Montana
ZIP/Postal Code
59715
Country
United States
City
Bellevue
State/Province
Nebraska
ZIP/Postal Code
68005
Country
United States
City
Freemont
State/Province
Nebraska
ZIP/Postal Code
68025
Country
United States
City
Haddon Heights
State/Province
New Jersey
ZIP/Postal Code
08035
Country
United States
City
Sicklerville
State/Province
New Jersey
ZIP/Postal Code
08081
Country
United States
City
Camillus
State/Province
New York
ZIP/Postal Code
13031
Country
United States
City
Endwell
State/Province
New York
ZIP/Postal Code
13780
Country
United States
City
Johnson City
State/Province
New York
ZIP/Postal Code
13790
Country
United States
City
Asheboro
State/Province
North Carolina
ZIP/Postal Code
27203
Country
United States
City
Burlington
State/Province
North Carolina
ZIP/Postal Code
27215
Country
United States
City
Greensboro
State/Province
North Carolina
ZIP/Postal Code
27408
Country
United States
City
Harrisburg
State/Province
North Carolina
ZIP/Postal Code
28075
Country
United States
City
Mooresville
State/Province
North Carolina
ZIP/Postal Code
28117
Country
United States
City
Morganton
State/Province
North Carolina
ZIP/Postal Code
28655
Country
United States
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27612
Country
United States
City
Salisbury
State/Province
North Carolina
ZIP/Postal Code
28144
Country
United States
City
Bismarck
State/Province
North Dakota
ZIP/Postal Code
58501
Country
United States
City
Canal Fulton
State/Province
Ohio
ZIP/Postal Code
44614
Country
United States
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44121
Country
United States
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44122
Country
United States
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73112
Country
United States
City
Ashland
State/Province
Oregon
ZIP/Postal Code
97520
Country
United States
City
Medford
State/Province
Oregon
ZIP/Postal Code
97504
Country
United States
City
Collegeville
State/Province
Pennsylvania
ZIP/Postal Code
19426
Country
United States
City
Erie
State/Province
Pennsylvania
ZIP/Postal Code
16506
Country
United States
City
Jefferson Hills
State/Province
Pennsylvania
ZIP/Postal Code
15025
Country
United States
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15236
Country
United States
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15241
Country
United States
City
Reading
State/Province
Pennsylvania
ZIP/Postal Code
19606
Country
United States
City
Scotland
State/Province
Pennsylvania
ZIP/Postal Code
17254
Country
United States
City
Upland
State/Province
Pennsylvania
ZIP/Postal Code
19013
Country
United States
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29412
Country
United States
City
Mt. Pleasant
State/Province
South Carolina
ZIP/Postal Code
29464
Country
United States
City
Simpsonville
State/Province
South Carolina
ZIP/Postal Code
29681
Country
United States
City
Bristol
State/Province
Tennessee
ZIP/Postal Code
37620
Country
United States
City
Jackson
State/Province
Tennessee
ZIP/Postal Code
38305
Country
United States
City
Johnson City
State/Province
Tennessee
ZIP/Postal Code
37604
Country
United States
City
Kingsport
State/Province
Tennessee
ZIP/Postal Code
37660
Country
United States
City
Bedford
State/Province
Texas
ZIP/Postal Code
76022
Country
United States
City
Corpus Christi
State/Province
Texas
ZIP/Postal Code
78411
Country
United States
City
Dallas
State/Province
Texas
ZIP/Postal Code
75220
Country
United States
City
El Paso
State/Province
Texas
ZIP/Postal Code
79912
Country
United States
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76109
Country
United States
City
New Braunfels
State/Province
Texas
ZIP/Postal Code
78130
Country
United States
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78215
Country
United States
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78238
Country
United States
City
Tomball
State/Province
Texas
ZIP/Postal Code
77375
Country
United States
City
Clinton
State/Province
Utah
ZIP/Postal Code
84015
Country
United States
City
Magna
State/Province
Utah
ZIP/Postal Code
84044
Country
United States
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84107
Country
United States
City
Saratoga Springs
State/Province
Utah
ZIP/Postal Code
84045
Country
United States
City
West Jordan
State/Province
Utah
ZIP/Postal Code
84088
Country
United States
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23219
Country
United States
City
Vienna
State/Province
Virginia
ZIP/Postal Code
22180
Country
United States
City
Spokane
State/Province
Washington
ZIP/Postal Code
99204
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Study of Tamiflu (Oseltamivir) for Treatment of Influenza With a Focus on (H1N1) 2009 Flu Strain
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