A Study of Oseltamivir (Tamiflu) for the Seasonal Prophylaxis of Influenza in Immunocompromised Participants

A Double-blind, Randomized, Placebo Controlled, Multi-center Trial of Oseltamivir for the Seasonal Prophylaxis of Influenza in Immunocompromised Patients

This 2 arm study will evaluate the efficacy and safety of oseltamivir in the seasonal prophylaxis of influenza in immunocompromised participants (as represented by transplant recipients). Transplant recipients enrolled when influenza is circulating in the community will be randomized to receive oseltamivir syrup or capsules 30 milligrams (mg) to 75 mg daily (depending on body weight) or placebo for 12 weeks. Influenza symptoms and safety data will be recorded throughout the study.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Drug: Oseltamivir; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 477
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Aalst, Belgium, 9300
  • Bruxelles, Belgium, 1200
  • Bruxelles, Belgium, 1090
  • Edegem, Belgium, 2650
  • Leuven, Belgium, 3000
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
  • British Columbia
    • Coquitlam, British Columbia, Canada, V3K 3P4
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 3P4
  • Ontario
    • London, Ontario, Canada, N6A 5A5
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7M 0Z9
• Czech Republic
  • Brno, Czech Republic, 639 00
• Estonia
  • Tallinn, Estonia, 10617
  • Tartu, Estonia, 51014
• France
  • Paris, France, 75743
  • Paris, France, 75475
  • Paris, France, 75019
  • Toulouse, France, 31054
  • Tours, France, 37044
• Germany
  • Aachen, Germany, 52057
  • Berlin, Germany, 10098
  • Hamburg, Germany, 20251
  • Heidelberg, Germany, 69120
  • München, Germany, 80336
  • München, Germany, 81675
• Hungary
  • Budapest, Hungary, 1097
  • Pecs, Hungary, 7624
  • Szeged, Hungary, 6720
• Israel
  • Jerusalem, Israel, 91120
  • Petach Tikva, Israel, 49100
  • Ramat Gan, Israel, 52621
• Italy
  • Padova, Italy, 35128
  • Pavia, Italy, 27100
  • Roma, Italy, 00168
• Lithuania
  • Kaunas, Lithuania, 50009
  • Vilnius, Lithuania, 08661
• Poland
  • Bialystok, Poland, 15-540
  • Lodz, Poland, 90-153
  • Szczecin, Poland, 70-111
  • Warszawa, Poland, 02-006
  • Warszawa, Poland, 04-730
• Spain
  • Madrid, Spain, 28006
  • Madrid, Spain, 28040
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
  • Edinburgh, United Kingdom, EH16 4SA
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
  • California
    • Stanford, California, United States, 94305
  • Colorado
    • Denver, Colorado, United States, 80262
  • Connecticut
    • Hartford, Connecticut, United States, 06106-3316
  • Delaware
    • Newark, Delaware, United States, 19718
  • Florida
    • St Petersburg, Florida, United States, 33701
  • Georgia
    • Atlanta, Georgia, United States, 30309
    • Augusta, Georgia, United States, 30912
  • Illinois
    • Chicago, Illinois, United States, 60611
    • Chicago, Illinois, United States, 60612
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
  • Michigan
    • Detroit, Michigan, United States, 48201
    • Detroit, Michigan, United States, 48202-2689
  • Minnesota
    • Brooklyn Center, Minnesota, United States, 55430
  • Montana
    • Missoula, Montana, United States, 59802
  • New Jersey
    • Camden, New Jersey, United States, 08103
    • Hackensack, New Jersey, United States, 07601
    • Livingston, New Jersey, United States, 07039
    • Newark, New Jersey, United States, 07112
  • New York
    • Buffalo, New York, United States, 14263
    • New York, New York, United States, 10032
    • New York, New York, United States, 10023
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7211
    • Charlotte, North Carolina, United States, 28207
    • Durham, North Carolina, United States, 27705
  • Ohio
    • Cincinnati, Ohio, United States, 45267
    • Cleveland, Ohio, United States, 44195
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112-44A1
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
    • Philadelphia, Pennsylvania, United States, 19104
    • Pittsburgh, Pennsylvania, United States, 15213
  • Texas
    • Dallas, Texas, United States, 75203
    • Houston, Texas, United States, 77030

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Negative rapid diagnostic test for influenza at baseline;
• Immunocompromised participant (liver and/or kidney recipient or allogenic hematopoietic stem cell transplant).

Exclusion Criteria:

• Symptoms suggestive of influenza-like illness; but not limited to fever, cough, or nasal congestion;
• Influenza vaccination in 6 weeks prior to randomization;
• Positive rapid diagnostic test for influenza;
• Solid organ transplant within 6 months of randomization;
• Antiviral treatment for influenza in 2 weeks prior to randomization.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo matched to oseltamivir capsule or suspension orally once daily for 12 weeks.
Experimental: Oseltamivir	Drug: Oseltamivir; Oseltamivir 30 mg to 75 mg capsule or suspension orally once daily for 12 weeks.; Other Names: Tamiflu

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Laboratory-Confirmed Clinical Influenza, ITT Population	Laboratory-confirmed clinical influenza was defined as a fever (oral or otic temperature greater than [>] 37.2 degrees Celsius [°C]) and a symptom score for cough and/or coryza (nasal congestion on the diary cards, where 0=absent, 1=mild, 2=moderate, and 3=severe) of 1, 2 or 3 on the same day as fever, and laboratory confirmation of influenza either by detection of viral shedding by viral culture from nasopharyngeal swabs within two days of fever and symptoms, and/or by 4-fold or greater increase in serum hemagglutination inhibition (HAI) titers measured from baseline to any point during the study.	From baseline up to 28 days after the last dose of study drug (maximum up to 112 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Laboratory Confirmed Clinical Influenza, Per Protocol (PP) Population	Laboratory-confirmed clinical influenza was defined as a fever (oral or otic temperature greater than 37.2 °C) and a symptom score for cough and/or coryza (nasal congestion on the diary cards, where 0=absent, 1=mild, 2=moderate, and 3=severe) of 1, 2 or 3 on the same day as fever, and laboratory confirmation of influenza either by detection of viral shedding by viral culture from nasopharyngeal swabs within two days of fever and symptoms, and/or by 4-fold or greater increase in serum HAI titers measured from baseline to any point during the study.	From baseline up to 28 days after the last dose of study drug (maximum up to 112 days)
Number of Participants With Laboratory Confirmed Clinical Influenza, Intent-to-treat Virus Negative at Baseline (ITTNAB) Population	Laboratory-confirmed clinical influenza was defined as a fever (oral or otic temperature greater than 37.2 °C) and a symptom score for cough and/or coryza (nasal congestion on the diary cards, where 0=absent, 1=mild, 2=moderate, and 3=severe) of 1, 2 or 3 on the same day as fever, and laboratory confirmation of influenza either by detection of viral shedding by viral culture from nasopharyngeal swabs within two days of fever and symptoms, and/or by 4-fold or greater increase in serum HAI titers measured from baseline to any point during the study.	From baseline up to 28 days after the last dose of study drug (maximum up to 112 days)
Number of Participants With Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) Confirmed Clinical Influenza, ITT Population	RT-PCR confirmed clinical influenza was defined as a confirmation of influenza by positive RT-PCR result within 2 days of symptoms/last dose from baseline to any point during the study.	From baseline up to 28 days after the last dose of study drug (maximum up to 112 days)
Number of Participants With RT-PCR Confirmed Clinical Influenza, ITTNAB Population	RT-PCR confirmed clinical influenza was defined as a confirmation of influenza by positive RT-PCR result within 2 days of symptoms/last dose from baseline to any point during the study.	From baseline up to 28 days after the last dose of study drug (maximum up to 112 days)
Number of Participants With RT-PCR, or Serology/Viral Culture Confirmed Clinical Influenza, ITT Population	RT-PCR, or serology/viral culture confirmed clinical influenza was defined as a confirmation of influenza by positive RT-PCR or culture within 2 days of symptoms/ last dose and/or positive serology result from baseline to any point during the study.	From baseline up to 28 days after the last dose of study drug (maximum up to 112 days)
Number of Participants With RT-PCR, or Serology/Viral Culture Confirmed Clinical Influenza, ITTNAB Population	RT-PCR, or serology/viral culture confirmed clinical influenza was defined as a confirmation of influenza by positive RT-PCR or culture within 2 days of symptoms/ last dose and/or positive serology result from baseline to any point during the study.	From baseline up to 28 days after the last dose of study drug (maximum up to 112 days)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Ison MG, Szakaly P, Shapira MY, Krivan G, Nist A, Dutkowski R. Efficacy and safety of oral oseltamivir for influenza prophylaxis in transplant recipients. Antivir Ther. 2012;17(6):955-64. doi: 10.3851/IMP2192. Epub 2012 Jun 22.

Helpful Links

• Clinical Study Report Synopsis

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): May 1, 2008
• Study Completion (Actual): May 1, 2008

Study Registration Dates

• First Submitted: December 15, 2006
• First Submitted That Met QC Criteria: December 15, 2006
• First Posted (Estimate): December 18, 2006

Study Record Updates

• Last Update Posted (Estimate): June 10, 2016
• Last Update Submitted That Met QC Criteria: May 4, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Oseltamivir
• Other Study ID Numbers: NV20235