A Study of Fluzone® High-Dose Vaccine Compared With Fluzone® Vaccine In Elderly Adults

Efficacy Study of Fluzone® High-Dose Vaccine Compared With Fluzone® Vaccine In Elderly Adults

The aim of this study is to determine the efficacy of Fluzone High-Dose compared to standard dose Fluzone for laboratory-confirmed or culture-confirmed influenza caused by influenza types/subtypes that are similar (for laboratory-confirmed) or antigenically similar (for culture-confirmed) to those contained in the respective annual vaccine formulations.

Primary Objective:

• To compare the clinical efficacy of Fluzone High-Dose to that of Fluzone in elderly adults, with respect to laboratory-confirmed influenza caused by any influenza viral types/subtypes, associated with the occurrence of a protocol-defined influenza-like-illnesses (ILI).

Secondary Objectives:

• To compare the clinical efficacy of Fluzone High-Dose to that of Fluzone in elderly adults, with respect to laboratory-confirmed influenza, caused by any influenza viral types/subtypes, associated with the occurrence of a protocol-defined ILI.
• To compare the clinical efficacy of Fluzone High-Dose to that of Fluzone in elderly adults, with respect to culture-confirmed influenza, caused by any influenza viral types/subtypes, associated with the occurrence of a protocol-defined ILI.
• To compare the clinical efficacy of Fluzone High-Dose to that of Fluzone in elderly adults, with respect to culture-confirmed influenza caused by viral types/subtypes antigenically similar to those contained in the respective annual vaccine formulations, associated with the occurrence of a modified Centers for Disease Control and Prevention (CDC)-defined ILI.
• To compare the clinical efficacy of Fluzone High-Dose to that of Fluzone in elderly adults, with respect to culture-confirmed influenza caused by any influenza viral types/subtypes, associated with the occurrence of a modified CDC-defined ILI.
• To compare the clinical efficacy of Fluzone High-Dose to that of Fluzone in elderly adults, with respect to culture-confirmed influenza caused by viral types/subtypes antigenically similar to those contained in the respective annual vaccine formulations, associated with the occurrence of a respiratory illness.
• To compare the clinical efficacy of Fluzone High-Dose to that of Fluzone in elderly adults, with respect to culture-confirmed influenza caused by any influenza viral types/subtypes, associated with the occurrence of a respiratory illness.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: High Dose Trivalent Inactivated Influenza Vaccine; Biological: Trivalent Inactivated Influenza Vaccine

Detailed Description

The trial will span 2 influenza seasons. Each study year, participants will be randomized to receive one dose of either Fluzone® High-Dose or Fluzone® vaccine prior to the start of the influenza season and will be followed until the end of each season.

The duration of each participant's participation in the respective study year will be 6 to 8 months, depending on the time of enrollment.

• Study Type: Interventional
• Enrollment (Actual): 31989
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Coquitlam, British Columbia, Canada, V3K3P4
  • Newfoundland and Labrador
    • Mount Pearl, Newfoundland and Labrador, Canada, A1N1W7
  • Nova Scotia
    • Truro, Nova Scotia, Canada, B2N1L2
  • Ontario
    • Sudbury, Ontario, Canada, P3E1H5
    • Toronto, Ontario, Canada, M9W4L6
  • Quebec
    • Sherbrooke, Quebec, Canada, J1H4J6
• Puerto Rico
  • Bayamon, Puerto Rico, 00961
  • San Juan, Puerto Rico, 00909
• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
  • Arizona
    • Chandler, Arizona, United States, 85224
    • Glendale, Arizona, United States, 85308
    • Glendale, Arizona, United States, 85306
    • Mesa, Arizona, United States, 85213
    • Mesa, Arizona, United States, 85203
    • Phoenix, Arizona, United States, 85020
    • Phoenix, Arizona, United States, 85050
    • Phoenix, Arizona, United States, 85028
    • Scottsdale, Arizona, United States, 85251
    • Tempe, Arizona, United States, 85283
  • Arkansas
    • Harrisburg, Arkansas, United States, 72432
  • California
    • Anaheim, California, United States, 92801
    • La Mesa, California, United States, 91942
    • Oceanside, California, United States, 92056
    • Redding, California, United States, 96001
    • San Diego, California, United States, 92103
    • Santa Rosa, California, United States, 95405
  • Colorado
    • Aurora, Colorado, United States, 80045
    • Colorado Springs, Colorado, United States, 80907
    • Colorado Springs, Colorado, United States, 80922
  • Connecticut
    • Milford, Connecticut, United States, 06460
    • Milford, Connecticut, United States, 01757
  • Florida
    • Brooksville, Florida, United States, 34601
    • Clearwater, Florida, United States, 33756
    • Clearwater, Florida, United States, 33761
    • Coral Gables, Florida, United States, 33134
    • Crystal River, Florida, United States, 34429
    • DeLand, Florida, United States, 32720
    • Jacksonville, Florida, United States, 32216
    • Melbourne, Florida, United States, 32935
    • Pembroke Pine, Florida, United States, 33026
    • Pinellas Park, Florida, United States, 33781
    • Sarasota, Florida, United States, 34231
  • Georgia
    • Stockbridge, Georgia, United States, 30281
  • Idaho
    • Boise, Idaho, United States, 83642
  • Illinois
    • Chicago, Illinois, United States, 60654
    • Peoria, Illinois, United States, 61602
  • Indiana
    • Mishawaka, Indiana, United States, 46545
  • Kansas
    • Lenexa, Kansas, United States, 66219
    • Newton, Kansas, United States, 67114
    • Overland Park, Kansas, United States, 66212
    • Prairie Village, Kansas, United States, 66206
    • Wichita, Kansas, United States, 67207
    • Wichita, Kansas, United States, 67205
  • Kentucky
    • Bardstown, Kentucky, United States, 40004
    • Lexington, Kentucky, United States, 40504
  • Maryland
    • Columbia, Maryland, United States, 21045
    • Elkridge, Maryland, United States, 21075
    • Rockville, Maryland, United States, 20850
  • Massachusetts
    • Brockton, Massachusetts, United States, 02301
    • Haverhill, Massachusetts, United States, 01830
  • Minnesota
    • Edina, Minnesota, United States, 55435
  • Missouri
    • Kansas City, Missouri, United States, 64114
    • St. Louis, Missouri, United States, 63141
  • Montana
    • Missoula, Montana, United States, 59808
  • Nebraska
    • Bellevue, Nebraska, United States, 68005
    • Omaha, Nebraska, United States, 68114
  • Nevada
    • Las Vega, Nevada, United States, 89104
  • New Hampshire
    • Newington, New Hampshire, United States, 03801
  • New Jersey
    • Edison, New Jersey, United States, 08817
  • New Mexico
    • Albuquerque, New Mexico, United States, 87018
  • New York
    • Binghamton, New York, United States, 13901
    • Endwell, New York, United States, 13760
    • Rochester, New York, United States, 14642
    • Rochester, New York, United States, 14609
  • North Carolina
    • Cary, North Carolina, United States, 27518
    • Charlotte, North Carolina, United States, 28209
    • Hickory, North Carolina, United States, 28602
    • Raleigh, North Carolina, United States, 27609
    • Raleigh, North Carolina, United States, 27612
    • Salisbury, North Carolina, United States, 28144
    • Wilmington, North Carolina, United States, 28401
    • Winston Salem, North Carolina, United States, 27103
  • North Dakota
    • Fargo, North Dakota, United States, 58104
    • Idaho Falls, North Dakota, United States, 83404
  • Ohio
    • Akron, Ohio, United States, 44311
    • Cincinnati, Ohio, United States, 45227
    • Cincinnati, Ohio, United States, 45259
    • Cleveland, Ohio, United States, 44122
    • Columbus, Ohio, United States, 43213
  • Oklahoma
    • Norman, Oklahoma, United States, 73069
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16506
    • Pittsburgh, Pennsylvania, United States, 15241
    • Scranton, Pennsylvania, United States, 18510
  • Rhode Island
    • Warwick, Rhode Island, United States, 02886
  • South Carolina
    • Anderson, South Carolina, United States, 29621
    • Clinton, South Carolina, United States, 29325
    • Greer, South Carolina, United States, 29650
    • Mt. Pleasant, South Carolina, United States, 29464
    • Spartanburg, South Carolina, United States, 29303
  • Tennessee
    • Bristol, Tennessee, United States, 37620
    • Nashville, Tennessee, United States, 37212
    • Nashville, Tennessee, United States, 37203
  • Texas
    • Fort Worth, Texas, United States, 76107
    • San Antonio, Texas, United States, 78229
    • Tomball, Texas, United States, 77375
  • Utah
    • Salt Lake City, Utah, United States, 84121
    • Salt Lake City, Utah, United States, 84109
    • Salt Lake City, Utah, United States, 84124
    • South Jordan, Utah, United States, 84095
    • West Jordan, Utah, United States, 84088
  • Virginia
    • Norfolk, Virginia, United States, 23507
    • Williamsburg, Virginia, United States, 23185
    • Winchester, Virginia, United States, 22601

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged ≥ 65 years on the day of vaccination
• Informed consent form signed and dated
• Able to attend all scheduled visits and to comply with all trial procedures.

Exclusion Criteria:

• Participation at the time of study enrollment (or in the 4 weeks preceding the trial vaccination), or planned participation during each year of the trial period, in another clinical trial investigating a vaccine, drug, medical device, or medical procedure (Note: Concomitant participation in an observational trial is acceptable)
• Vaccination against influenza in the 6 months preceding the trial vaccination
• Systemic hypersensitivity to eggs, chicken proteins, or any of the vaccine components, or a history of a life-threatening reaction to Fluzone High-Dose or Fluzone vaccine or to a vaccine containing any of the same substances
• Personal history of Guillain-Barré Syndrome
• Dementia or any other cognitive condition at a stage that could interfere with following the trial procedures
• Thrombocytopenia contraindicating intramuscular (IM) vaccination, as judged by the investigator
• Bleeding disorder or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination, as judged by the investigator
• Current alcohol abuse or drug addiction
• Subject deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily
• Identified as an Investigator or employee of the Investigator or study center with direct involvement in the proposed study, or identified as an immediate family member (i.e., parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study
• Moderate or severe acute illness with or without fever (oral temperature > 99.0ºF [> 37.2ºC]). If this contraindication exists, vaccination will be deferred until the individual has been medically stable and/or afebrile (temperature ≤ 99.0 ºF [≤ 37.2ºC]) for at least 24 hours
• Signs and symptoms of an acute infectious respiratory illness. If this exists, vaccination will be deferred until the symptoms resolve.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High Dose Trivalent Inactivated Influenza Vaccine; Participants will receive an injection of High Dose Trivalent Inactivated Influenza Vaccine	Biological: High Dose Trivalent Inactivated Influenza Vaccine; 0.5 mL Intramuscular; Other Names: Fluzone® High Dose
Active Comparator: Trivalent Inactivated Influenza Vaccine; Participants will receive an injection of the Trivalent Inactivated Influenza vaccine	Biological: Trivalent Inactivated Influenza Vaccine; 0.5 mL, Intramuscular; Other Names: Fluzone®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrences of Culture- or Polymerase Chain Reaction (PCR)-Confirmed Influenza Caused by Any Influenza Viral Types/Subtypes, in Association With a Protocol-defined Influenza-like Illness (ILI).	Influenza positive cultures were confirmed using direct immunofluorescence techniques with influenza type-specific antibodies. 3 culture methods were utilized for each NP sample (Classic Flu A and B culture using Madin Darby Canine Kidney cells, Classic Flu A and B culture using Rhesus Monkey Kidney cells, and R Mix Flu A and B culture). The initial molecular test (PCR) was the validated ProFlu+™ assay by Prodesse, Inc., Waukesha, WI, which had been approved by the Food and Drug Administration through a 510K evaluation for specific detection of Influenza A, B or Respiratory Syncytial Virus. A protocol-defined influenza-like illness was determined by the occurrence of at least 1 of the following respiratory symptoms: sore throat, cough, sputum production, wheezing, or difficulty breathing; concurrently with at least one of the following systemic symptoms: fever (defined as temperature > 99.0°F [> 37.2°C]), chills (shivering), tiredness (fatigue), headache, or myalgia (muscle aches).	≥14 days post-vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrences of Culture-confirmed Influenza Caused by Influenza Viral Types/Subtypes That Are Antigenically Similar to Those Contained in the Vaccine Formulations, in Association With a Protocol-defined Influenza-like Illness (ILI)	Influenza positive cultures were confirmed by using direct immunofluorescence techniques with influenza type-specific (i.e., for Influenza A and Influenza B) antibodies. For culture confirmation of influenza, 3 different culture methods were utilized for each NP sample (Classic Flu A and B culture using Madin Darby Canine Kidney [MDCK] cells, Classic Flu A and B culture using Rhesus Monkey Kidney [RhMK] cells, and R Mix Flu A and B culture. For antigenic similarity determinations, a standard hemagglutination inhibition test using a panel of ferret antisera (ferret antigenicity testing) was used.	≥14 days post-vaccination
Occurrences of Culture-confirmed Influenza Caused by Any Influenza Viral Types/Subtypes, in Association With a Protocol-defined Influenza-like Illness	For culture confirmation of influenza, 3 different culture methods were utilized for each NP sample (Classic Flu A and B culture using Madin Darby Canine Kidney [MDCK] cells, Classic Flu A and B culture using Rhesus Monkey Kidney [RhMK] cells, and R Mix Flu A and B culture). A protocol-defined influenza-like illness (ILI) was determined by the occurrence of at least one of the following respiratory symptoms: sore throat, cough, sputum production, wheezing, or difficulty breathing; concurrently with at least one of the following systemic symptoms: fever (defined as temperature > 99.0°F [> 37.2°C]), chills (shivering), tiredness (fatigue), headache, or myalgia (muscle aches).	≥14 days post-vaccination
Occurrences of Culture-confirmed Influenza Caused by Influenza Viral Types/Subtypes That Are Antigenically Similar to Those Contained in the Vaccine Formulations, in Association With a Modified CDC-defined Influenza-like Illness.	Influenza positive cultures were confirmed by using direct immunofluorescence techniques with influenza type-specific antibodies. For culture confirmation of influenza, 3 different culture methods were utilized for each NP sample (Classic Flu A and B culture using Madin Darby Canine Kidney cells, Classic Flu A and B culture using Rhesus Monkey Kidney cells, and R Mix Flu A and B culture). For antigenic similarity determinations, a standard hemagglutination inhibition test using a panel of ferret antisera (ferret antigenicity testing) was used. The modified Centers for Disease Control and Prevention-defined influenza-like illness is the occurrence of fever (defined as temperature > 99.0°F [> 37.2°C]) with cough or sore throat.	≥14 days post-vaccination
Occurrences of Culture-confirmed Influenza Caused by Any Influenza Viral Types/Subtypes, in Association With a Modified CDC-defined Influenza-like Illness	Influenza positive cultures were confirmed by using direct immunofluorescence techniques with influenza type-specific antibodies. For culture confirmation of influenza, 3 different culture methods were utilized for each NP sample (Classic Flu A and B culture using Madin Darby Canine Kidney cells, Classic Flu A and B culture using Rhesus Monkey Kidney cells, and R Mix Flu A and B culture). For antigenic similarity determinations, a standard hemagglutination inhibition test using a panel of ferret antisera (ferret antigenicity testing) was used. The modified Centers for Disease Control and Prevention-defined influenza-like illness is the occurrence of fever (defined as temperature > 99.0°F [> 37.2°C]) with cough or sore throat.	≥14 days post-vaccination
Occurrences of Culture-confirmed Influenza Caused by Influenza Viral Types/Subtypes That Are Antigenically Similar to Those Contained in the Vaccine Formulations, in Association With a Respiratory Illness	Influenza positive cultures were confirmed by using direct immunofluorescence techniques with influenza type-specific antibodies. For culture confirmation of influenza, 3 different culture methods were utilized for each NP sample (Classic Flu A and B culture using Madin Darby Canine Kidney cells, Classic Flu A and B culture using Rhesus Monkey Kidney cells, and R Mix Flu A and B culture). For antigenic similarity determinations, a standard hemagglutination inhibition test using a panel of ferret antisera (ferret antigenicity testing) was used. Respiratory illness was defined as the occurrence of a new onset (or exacerbation of a pre-existing condition/symptom) of one or more of the following symptoms (that persist for or reoccur after a period of at least 12 hours): sneezing, stuffy or runny nose (nasal congestion), sore throat, cough, sputum production, wheezing, or difficulty breathing.	≥14 days post-vaccination
Occurrences of Culture-confirmed Influenza Caused by Any Influenza Viral Types/Subtypes, in Association With a Respiratory Illness	Influenza positive cultures were confirmed by using direct immunofluorescence techniques with influenza type-specific (i.e., for Influenza A and Influenza B) antibodies. For culture confirmation of influenza, 3 different culture methods were utilized for each NP sample (Classic Flu A and B culture using Madin Darby Canine Kidney cells, Classic Flu A and B culture using Rhesus Monkey Kidney cells, and R Mix Flu A and B culture). Respiratory illness is defined as the occurrence of a new onset (or exacerbation of a pre-existing condition/symptom) of one or more of the following symptoms (that persist for or reoccur after a period of at least 12 hours): sneezing, stuffy or runny nose (nasal congestion), sore throat, cough, sputum production, wheezing, or difficulty breathing.	≥14 days post-vaccination

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Overview After Injection With Either Fluzone High Dose or Fluzone Vaccine Through the End of Surveillance Period	All serious adverse events, including deaths and adverse events (AEs) of special interest (Guillain Barre Syndrome, Bell's Palsy, encephalitis/myelitis, optic neuritis, Stevens Johnson Syndrome, and toxic epidermal necrolysis) were collected.	Day 0 up to Day 240 post-vaccination

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company

Publications and helpful links

General Publications

• DiazGranados CA, Dunning AJ, Kimmel M, Kirby D, Treanor J, Collins A, Pollak R, Christoff J, Earl J, Landolfi V, Martin E, Gurunathan S, Nathan R, Greenberg DP, Tornieporth NG, Decker MD, Talbot HK. Efficacy of high-dose versus standard-dose influenza vaccine in older adults. N Engl J Med. 2014 Aug 14;371(7):635-45. doi: 10.1056/NEJMoa1315727.
• Becker DL, Chit A, DiazGranados CA, Maschio M, Yau E, Drummond M. High-dose inactivated influenza vaccine is associated with cost savings and better outcomes compared to standard-dose inactivated influenza vaccine in Canadian seniors. Hum Vaccin Immunother. 2016 Dec;12(12):3036-3042. doi: 10.1080/21645515.2016.1215395. Epub 2016 Sep 26.
• Dunning AJ, DiazGranados CA, Voloshen T, Hu B, Landolfi VA, Talbot HK. Correlates of Protection against Influenza in the Elderly: Results from an Influenza Vaccine Efficacy Trial. Clin Vaccine Immunol. 2016 Jan 13;23(3):228-35. doi: 10.1128/CVI.00604-15.

Helpful Links

• Related Info
• Related Info

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: August 30, 2011
• First Submitted That Met QC Criteria: August 30, 2011
• First Posted (Estimate): September 1, 2011

Study Record Updates

• Last Update Posted (Estimate): April 20, 2015
• Last Update Submitted That Met QC Criteria: March 30, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Influenza; Trivalent Inactivated Influenza Vaccine; High-Dose Trivalent Inactivated Influenza Vaccine; Fluzone® High-Dose; Influenza vaccines
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: FIM12; U1111-1120-1300 (Other Identifier: WHO)