Influenza
Conditions
Keywords
Influenza, Respiratory Tract Infections, Influenza-like illness, Elderly, Fluzone®, Efficacy
Brief summary
The aim of this study is to determine the efficacy of Fluzone High Dose vaccine and that of Fluzone® vaccine in the elderly. Primary objective: To measure the efficacy of the vaccine, defined as the prevention of laboratory-confirmed influenza caused by viral types/subtypes that are antigenically similar to those contained in the respective annual vaccine formulations. Secondary objectives: * To compare the clinical efficacy of Fluzone High Dose vaccine with that of Fluzone® vaccine in elderly adults, with respect to laboratory-confirmed influenza illness caused by any type or subtype of influenza virus. * To compare the clinical efficacy of Fluzone High Dose vaccine with that of Fluzone® vaccine in elderly adults, in preventing culture-confirmed influenza illness caused by viral types/subtypes antigenically similar to those contained in the respective annual vaccine formulations.
Detailed description
The occurrence of influenza-like illness (ILI) will be determined in elderly participants vaccinated with either Fluzone High Dose or Fluzone® vaccine. The presence of influenza virus in the respiratory tract of vaccinated individuals with ILI will be confirmed by two methods.
Interventions
BIOLOGICALTrivalent inactivated influenza vaccine High Dose
0.5 mL, Intramuscular
BIOLOGICALTrivalent inactivated influenza vaccine
0.5 mL, Intramuscular
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
Yes
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 in another interventional clinical trial investigating a vaccine, drug, medical device, herbal supplement, or a medical procedure in the 4 weeks preceding the trial vaccination or planned participation in another clinical trial investigating a vaccine, drug, medical device, herbal supplement, or a medical procedure during each year of participation in the study trial. * 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 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, bleeding disorder, or anticoagulation therapy contraindicating intramuscular (IM) vaccination. * Known or suspected human immunodeficiency virus (HIV), Hepatitis B surface antigen (HBsAg), or Hepatitis C seropositivity. * Alcohol abuse or drug addiction that could interfere with the subject's ability to comply with trial procedures. * Subject deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized without his/her consent. * Bedridden subjects.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of Fluzone High Dose Relative to Fluzone in the Prevention of Laboratory Confirmed Influenza Caused by Viral Types and Subtypes That Are Antigenically Similar to Those Contained in the Respective Annual Vaccine Formulations. | Day 0 (pre-vaccination) up to Year 1 post-vaccination | The presence (and specific identification) of influenza virus in the respiratory tract of vaccinated individuals with influenza like illness (ILI) was confirmed by tissue culture (for infectious virus) and molecular techniques (polymerase chain reaction based assays), with results reported for cases cause by any viral type or subtype. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Reporting Events Associated With All Cases of Protocol Defined Influenza-Like Illness (ILI) | Day 0 (pre-vaccination) up to the end of the influenza season | Events associated with Protocol defined influenza-like Illnesses (ILI) were defined as pneumonia, new onset or exacerbation of pre-existing cardio respiratory conditions, health care visits, and medication use (including nonsteroidal anti-inflammatory drugs, NSAIDs). |
| Number of Participants Reporting Events Associated With All Cases of CDC Defined Influenza-Like Illness (ILI) | Day 14 (post-vaccination) up to 12 Months post-vaccination | Events associated with CDC defined influenza-like Illnesses (ILI) were defined as pneumonia, new onset or exacerbation of pre existing cardio respiratory conditions, health care visits, and medication use (including nonsteroidal anti-inflammatory drugs, NSAIDs). |
| Number of Participants Reporting Adverse Events of Special Interest (AESIs) and Serious Adverse Events Post-vaccination With Either Fluzone High-Dose and Fluzone | Day 0 before vaccination to Day 180 after vaccination | Adverse events of special interest: new onset of Guillain Barre Syndrome (GBS), Bell's Palsy, encephalitis or myelitis, optic neuritis, Stevens Johnson Syndrome, and toxic epidermal necrolysis |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
Participants were enrolled in the study from 22 September 2009 to 07 November 2009 at 99 clinical centers in the US.
Pre-assignment details
A total of 9158 of the 9172 participants that were randomized were vaccinated, evaluated, and reported in this report.
Participants by arm
| Arm | Count |
|---|---|
| Fluzone® High Dose All participants received a single dose of Fluzone High Dose vaccine on Day 0. | 6,108 |
| Fluzone® All subjects received a single dose of Fluzone vaccine on Day 0. | 3,050 |
| Total | 9,158 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
| Overall Study | Lost to Follow-up | 208 | 103 |
| Overall Study | Protocol Violation | 60 | 27 |
| Overall Study | Serious Adverse Event | 36 | 17 |
| Overall Study | Withdrawal by Subject | 107 | 66 |
Baseline characteristics
| Characteristic | Fluzone® | Fluzone® High Dose | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3050 Participants | 6108 Participants | 9158 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age Continuous | 72.8 Years STANDARD_DEVIATION 5.9 | 72.8 Years STANDARD_DEVIATION 6 | 72.8 Years STANDARD_DEVIATION 6 |
| Region of Enrollment United States | 3050 Participants | 6108 Participants | 9158 Participants |
| Sex: Female, Male Female | 1647 Participants | 3268 Participants | 4915 Participants |
| Sex: Female, Male Male | 1403 Participants | 2840 Participants | 4243 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 6,108 | 0 / 3,050 |
| serious Total, serious adverse events | 493 / 6,108 | 236 / 3,050 |
Outcome results
Primary
Efficacy of Fluzone High Dose Relative to Fluzone in the Prevention of Laboratory Confirmed Influenza Caused by Viral Types and Subtypes That Are Antigenically Similar to Those Contained in the Respective Annual Vaccine Formulations.
The presence (and specific identification) of influenza virus in the respiratory tract of vaccinated individuals with influenza like illness (ILI) was confirmed by tissue culture (for infectious virus) and molecular techniques (polymerase chain reaction based assays), with results reported for cases cause by any viral type or subtype.
Time frame: Day 0 (pre-vaccination) up to Year 1 post-vaccination
Population: Efficacy was assessed in all participants who met all study inclusion criteria and none of the exclusion criteria, received the vaccine to which they were randomized, and had no protocol violations that might have interfered with evaluation of primary endpoints (Per Protocol Analysis Set).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fluzone® High Dose | Efficacy of Fluzone High Dose Relative to Fluzone in the Prevention of Laboratory Confirmed Influenza Caused by Viral Types and Subtypes That Are Antigenically Similar to Those Contained in the Respective Annual Vaccine Formulations. | Culture Confirmed Cases of ILI | 13 Participants |
| Fluzone® High Dose | Efficacy of Fluzone High Dose Relative to Fluzone in the Prevention of Laboratory Confirmed Influenza Caused by Viral Types and Subtypes That Are Antigenically Similar to Those Contained in the Respective Annual Vaccine Formulations. | Laboratory Confirmed Cases of ILI | 14 Participants |
| Fluzone® High Dose | Efficacy of Fluzone High Dose Relative to Fluzone in the Prevention of Laboratory Confirmed Influenza Caused by Viral Types and Subtypes That Are Antigenically Similar to Those Contained in the Respective Annual Vaccine Formulations. | PCR Confirmed Cases of ILI | 14 Participants |
| Fluzone® | Efficacy of Fluzone High Dose Relative to Fluzone in the Prevention of Laboratory Confirmed Influenza Caused by Viral Types and Subtypes That Are Antigenically Similar to Those Contained in the Respective Annual Vaccine Formulations. | Laboratory Confirmed Cases of ILI | 8 Participants |
| Fluzone® | Efficacy of Fluzone High Dose Relative to Fluzone in the Prevention of Laboratory Confirmed Influenza Caused by Viral Types and Subtypes That Are Antigenically Similar to Those Contained in the Respective Annual Vaccine Formulations. | Culture Confirmed Cases of ILI | 7 Participants |
| Fluzone® | Efficacy of Fluzone High Dose Relative to Fluzone in the Prevention of Laboratory Confirmed Influenza Caused by Viral Types and Subtypes That Are Antigenically Similar to Those Contained in the Respective Annual Vaccine Formulations. | PCR Confirmed Cases of ILI | 8 Participants |
Other Pre-specified
Number of Participants Reporting Adverse Events of Special Interest (AESIs) and Serious Adverse Events Post-vaccination With Either Fluzone High-Dose and Fluzone
Adverse events of special interest: new onset of Guillain Barre Syndrome (GBS), Bell's Palsy, encephalitis or myelitis, optic neuritis, Stevens Johnson Syndrome, and toxic epidermal necrolysis
Time frame: Day 0 before vaccination to Day 180 after vaccination
Population: Adverse events of special interest were assessed in all participants who received study vaccine (Full Analysis Set).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fluzone® High Dose | Number of Participants Reporting Adverse Events of Special Interest (AESIs) and Serious Adverse Events Post-vaccination With Either Fluzone High-Dose and Fluzone | Stevens Johnson Syndrome | 0 Participants |
| Fluzone® High Dose | Number of Participants Reporting Adverse Events of Special Interest (AESIs) and Serious Adverse Events Post-vaccination With Either Fluzone High-Dose and Fluzone | Toxic Epidermal Necrolysis | 0 Participants |
| Fluzone® High Dose | Number of Participants Reporting Adverse Events of Special Interest (AESIs) and Serious Adverse Events Post-vaccination With Either Fluzone High-Dose and Fluzone | Serious Adverse Events (SAE) | 493 Participants |
| Fluzone® High Dose | Number of Participants Reporting Adverse Events of Special Interest (AESIs) and Serious Adverse Events Post-vaccination With Either Fluzone High-Dose and Fluzone | Death | 31 Participants |
| Fluzone® High Dose | Number of Participants Reporting Adverse Events of Special Interest (AESIs) and Serious Adverse Events Post-vaccination With Either Fluzone High-Dose and Fluzone | Guillain Barre Syndrome | 0 Participants |
| Fluzone® High Dose | Number of Participants Reporting Adverse Events of Special Interest (AESIs) and Serious Adverse Events Post-vaccination With Either Fluzone High-Dose and Fluzone | Bell's Palsy | 3 Participants |
| Fluzone® High Dose | Number of Participants Reporting Adverse Events of Special Interest (AESIs) and Serious Adverse Events Post-vaccination With Either Fluzone High-Dose and Fluzone | Encephalitis or Myelitis | 1 Participants |
| Fluzone® High Dose | Number of Participants Reporting Adverse Events of Special Interest (AESIs) and Serious Adverse Events Post-vaccination With Either Fluzone High-Dose and Fluzone | Optic Neuritis | 0 Participants |
| Fluzone® High Dose | Number of Participants Reporting Adverse Events of Special Interest (AESIs) and Serious Adverse Events Post-vaccination With Either Fluzone High-Dose and Fluzone | SAE Leading to Study Discontinuation | 36 Participants |
| Fluzone® High Dose | Number of Participants Reporting Adverse Events of Special Interest (AESIs) and Serious Adverse Events Post-vaccination With Either Fluzone High-Dose and Fluzone | Related SAE | 2 Participants |
| Fluzone® High Dose | Number of Participants Reporting Adverse Events of Special Interest (AESIs) and Serious Adverse Events Post-vaccination With Either Fluzone High-Dose and Fluzone | Related SAE Leading to Study Discontinuation | 0 Participants |
| Fluzone® | Number of Participants Reporting Adverse Events of Special Interest (AESIs) and Serious Adverse Events Post-vaccination With Either Fluzone High-Dose and Fluzone | SAE Leading to Study Discontinuation | 17 Participants |
| Fluzone® | Number of Participants Reporting Adverse Events of Special Interest (AESIs) and Serious Adverse Events Post-vaccination With Either Fluzone High-Dose and Fluzone | Stevens Johnson Syndrome | 0 Participants |
| Fluzone® | Number of Participants Reporting Adverse Events of Special Interest (AESIs) and Serious Adverse Events Post-vaccination With Either Fluzone High-Dose and Fluzone | Encephalitis or Myelitis | 0 Participants |
| Fluzone® | Number of Participants Reporting Adverse Events of Special Interest (AESIs) and Serious Adverse Events Post-vaccination With Either Fluzone High-Dose and Fluzone | Related SAE Leading to Study Discontinuation | 0 Participants |
| Fluzone® | Number of Participants Reporting Adverse Events of Special Interest (AESIs) and Serious Adverse Events Post-vaccination With Either Fluzone High-Dose and Fluzone | Serious Adverse Events (SAE) | 236 Participants |
| Fluzone® | Number of Participants Reporting Adverse Events of Special Interest (AESIs) and Serious Adverse Events Post-vaccination With Either Fluzone High-Dose and Fluzone | Optic Neuritis | 0 Participants |
| Fluzone® | Number of Participants Reporting Adverse Events of Special Interest (AESIs) and Serious Adverse Events Post-vaccination With Either Fluzone High-Dose and Fluzone | Death | 12 Participants |
| Fluzone® | Number of Participants Reporting Adverse Events of Special Interest (AESIs) and Serious Adverse Events Post-vaccination With Either Fluzone High-Dose and Fluzone | Toxic Epidermal Necrolysis | 0 Participants |
| Fluzone® | Number of Participants Reporting Adverse Events of Special Interest (AESIs) and Serious Adverse Events Post-vaccination With Either Fluzone High-Dose and Fluzone | Guillain Barre Syndrome | 0 Participants |
| Fluzone® | Number of Participants Reporting Adverse Events of Special Interest (AESIs) and Serious Adverse Events Post-vaccination With Either Fluzone High-Dose and Fluzone | Related SAE | 2 Participants |
| Fluzone® | Number of Participants Reporting Adverse Events of Special Interest (AESIs) and Serious Adverse Events Post-vaccination With Either Fluzone High-Dose and Fluzone | Bell's Palsy | 2 Participants |
Other Pre-specified
Number of Participants Reporting Events Associated With All Cases of CDC Defined Influenza-Like Illness (ILI)
Events associated with CDC defined influenza-like Illnesses (ILI) were defined as pneumonia, new onset or exacerbation of pre existing cardio respiratory conditions, health care visits, and medication use (including nonsteroidal anti-inflammatory drugs, NSAIDs).
Time frame: Day 14 (post-vaccination) up to 12 Months post-vaccination
Population: The occurrence of events associated with CDC defined ILI was assessed in all participants who met all study inclusion and exclusion criteria, received the vaccine to which they were randomized, and had no protocol violations that might have interfered with evaluation of primary endpoints (Per-Protocol Analysis Set).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fluzone® High Dose | Number of Participants Reporting Events Associated With All Cases of CDC Defined Influenza-Like Illness (ILI) | Any Health Care Visit | 145 Participants |
| Fluzone® High Dose | Number of Participants Reporting Events Associated With All Cases of CDC Defined Influenza-Like Illness (ILI) | Non Routine Medical Office Visits | 129 Participants |
| Fluzone® High Dose | Number of Participants Reporting Events Associated With All Cases of CDC Defined Influenza-Like Illness (ILI) | New Onset or Exacerbation of Cardio Respiratory | 3 Participants |
| Fluzone® High Dose | Number of Participants Reporting Events Associated With All Cases of CDC Defined Influenza-Like Illness (ILI) | Any Medication Use (Taken or Prescribed) | 220 Participants |
| Fluzone® High Dose | Number of Participants Reporting Events Associated With All Cases of CDC Defined Influenza-Like Illness (ILI) | Hospitalization | 12 Participants |
| Fluzone® High Dose | Number of Participants Reporting Events Associated With All Cases of CDC Defined Influenza-Like Illness (ILI) | Antipyretics, NSAIDs, Analgesics Use | 153 Participants |
| Fluzone® High Dose | Number of Participants Reporting Events Associated With All Cases of CDC Defined Influenza-Like Illness (ILI) | Pneumonia | 13 Participants |
| Fluzone® High Dose | Number of Participants Reporting Events Associated With All Cases of CDC Defined Influenza-Like Illness (ILI) | Antiviral Use | 17 Participants |
| Fluzone® High Dose | Number of Participants Reporting Events Associated With All Cases of CDC Defined Influenza-Like Illness (ILI) | Emergency Room Visit | 14 Participants |
| Fluzone® High Dose | Number of Participants Reporting Events Associated With All Cases of CDC Defined Influenza-Like Illness (ILI) | Antibiotic Use | 123 Participants |
| Fluzone® | Number of Participants Reporting Events Associated With All Cases of CDC Defined Influenza-Like Illness (ILI) | Antibiotic Use | 67 Participants |
| Fluzone® | Number of Participants Reporting Events Associated With All Cases of CDC Defined Influenza-Like Illness (ILI) | Pneumonia | 7 Participants |
| Fluzone® | Number of Participants Reporting Events Associated With All Cases of CDC Defined Influenza-Like Illness (ILI) | New Onset or Exacerbation of Cardio Respiratory | 1 Participants |
| Fluzone® | Number of Participants Reporting Events Associated With All Cases of CDC Defined Influenza-Like Illness (ILI) | Any Health Care Visit | 82 Participants |
| Fluzone® | Number of Participants Reporting Events Associated With All Cases of CDC Defined Influenza-Like Illness (ILI) | Hospitalization | 6 Participants |
| Fluzone® | Number of Participants Reporting Events Associated With All Cases of CDC Defined Influenza-Like Illness (ILI) | Emergency Room Visit | 9 Participants |
| Fluzone® | Number of Participants Reporting Events Associated With All Cases of CDC Defined Influenza-Like Illness (ILI) | Non Routine Medical Office Visits | 76 Participants |
| Fluzone® | Number of Participants Reporting Events Associated With All Cases of CDC Defined Influenza-Like Illness (ILI) | Any Medication Use (Taken or Prescribed) | 132 Participants |
| Fluzone® | Number of Participants Reporting Events Associated With All Cases of CDC Defined Influenza-Like Illness (ILI) | Antipyretics, NSAIDs, Analgesics Use | 94 Participants |
| Fluzone® | Number of Participants Reporting Events Associated With All Cases of CDC Defined Influenza-Like Illness (ILI) | Antiviral Use | 6 Participants |
Other Pre-specified
Number of Participants Reporting Events Associated With All Cases of Protocol Defined Influenza-Like Illness (ILI)
Events associated with Protocol defined influenza-like Illnesses (ILI) were defined as pneumonia, new onset or exacerbation of pre-existing cardio respiratory conditions, health care visits, and medication use (including nonsteroidal anti-inflammatory drugs, NSAIDs).
Time frame: Day 0 (pre-vaccination) up to the end of the influenza season
Population: The occurrence of events associated with ILI was assessed in all participants who met all study inclusion and exclusion criteria, received the vaccine to which they were randomized, and had no protocol violations that might have interfered with evaluation of primary endpoints (Per-Protocol Analysis Set).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fluzone® High Dose | Number of Participants Reporting Events Associated With All Cases of Protocol Defined Influenza-Like Illness (ILI) | Pneumonia | 28 Participants |
| Fluzone® High Dose | Number of Participants Reporting Events Associated With All Cases of Protocol Defined Influenza-Like Illness (ILI) | Hospitalization | 31 Participants |
| Fluzone® High Dose | Number of Participants Reporting Events Associated With All Cases of Protocol Defined Influenza-Like Illness (ILI) | Any Medication Use (Taken or Prescribed) | 781 Participants |
| Fluzone® High Dose | Number of Participants Reporting Events Associated With All Cases of Protocol Defined Influenza-Like Illness (ILI) | Emergency Room Visit | 40 Participants |
| Fluzone® High Dose | Number of Participants Reporting Events Associated With All Cases of Protocol Defined Influenza-Like Illness (ILI) | Cardio Respiratory Conditions | 10 Participants |
| Fluzone® High Dose | Number of Participants Reporting Events Associated With All Cases of Protocol Defined Influenza-Like Illness (ILI) | Antipyretics, NSAIDs, Analgesics Use | 552 Participants |
| Fluzone® High Dose | Number of Participants Reporting Events Associated With All Cases of Protocol Defined Influenza-Like Illness (ILI) | Antiviral Use | 37 Participants |
| Fluzone® High Dose | Number of Participants Reporting Events Associated With All Cases of Protocol Defined Influenza-Like Illness (ILI) | Any Health Care Visit | 478 Participants |
| Fluzone® High Dose | Number of Participants Reporting Events Associated With All Cases of Protocol Defined Influenza-Like Illness (ILI) | Antibiotic Use | 374 Participants |
| Fluzone® High Dose | Number of Participants Reporting Events Associated With All Cases of Protocol Defined Influenza-Like Illness (ILI) | Non Routine Medical Office Visits | 439 Participants |
| Fluzone® | Number of Participants Reporting Events Associated With All Cases of Protocol Defined Influenza-Like Illness (ILI) | Antibiotic Use | 194 Participants |
| Fluzone® | Number of Participants Reporting Events Associated With All Cases of Protocol Defined Influenza-Like Illness (ILI) | Non Routine Medical Office Visits | 226 Participants |
| Fluzone® | Number of Participants Reporting Events Associated With All Cases of Protocol Defined Influenza-Like Illness (ILI) | Any Medication Use (Taken or Prescribed) | 402 Participants |
| Fluzone® | Number of Participants Reporting Events Associated With All Cases of Protocol Defined Influenza-Like Illness (ILI) | Pneumonia | 14 Participants |
| Fluzone® | Number of Participants Reporting Events Associated With All Cases of Protocol Defined Influenza-Like Illness (ILI) | Cardio Respiratory Conditions | 6 Participants |
| Fluzone® | Number of Participants Reporting Events Associated With All Cases of Protocol Defined Influenza-Like Illness (ILI) | Any Health Care Visit | 245 Participants |
| Fluzone® | Number of Participants Reporting Events Associated With All Cases of Protocol Defined Influenza-Like Illness (ILI) | Hospitalization | 18 Participants |
| Fluzone® | Number of Participants Reporting Events Associated With All Cases of Protocol Defined Influenza-Like Illness (ILI) | Emergency Room Visit | 19 Participants |
| Fluzone® | Number of Participants Reporting Events Associated With All Cases of Protocol Defined Influenza-Like Illness (ILI) | Antipyretics, NSAIDs, Analgesics Use | 289 Participants |
| Fluzone® | Number of Participants Reporting Events Associated With All Cases of Protocol Defined Influenza-Like Illness (ILI) | Antiviral Use | 12 Participants |