Influenza
Conditions
Keywords
Influenza, Live attenuated influenza vaccine, Inactivated influenza vaccine, Vaccine Efficacy
Brief summary
The purpose of this study is to evaluate the absolute (versus placebo) and relative (one vaccine compared to the other) efficacies of the live attenuated and inactivated influenza vaccines in preventing laboratory confirmed symptomatic influenza caused by circulating strains whether similar or dissimilar to strains included in the vaccines.
Interventions
BIOLOGICALFluzone
single dose licensed trivalent inactivated influenza vaccine (2007-08)
BIOLOGICALFlumist
single dose licensed live-attenuated influenza vaccine Flumist (2007-08)
OTHERPhysiologic saline
single dose placebo administered as an intranasal spray or intramuscular injection
Sponsors
Sanofi Pasteur, a Sanofi Company
University of Michigan
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 49 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy adult men and women * Age 18-49 years * Who reside geographically close to one of the four study sites in Michigan
Exclusion criteria
* Persons with any of the health conditions for which the inactivated vaccine is recommended * Persons for whom either vaccine is contraindicated
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Laboratory-confirmed (Culture and/or PCR) Symptomatic Influenza | one influenza season - 2007-2008 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Measure Immune Response Induced by the Vaccines and Identify Serologic Correlates of Immune Protection | Time between prevaccination visit and postvaccination visit; typically about 30 days. | Measure immune response induced by the vaccines. Response was defined as greater than or equal to 4 fold rise in antibody titers measured by hemagglutination inhibition (HAI), microneutralization (MN), or neuraminidase inhibition (NAI) assays between sera collected at the prevaccination visit and those collected at the postvaccination visit. |
| Immune Response to Vaccination and Infection | Postvaccination to postseason visit; typically about 3 months. | Response was defined as greater than or equal to 4 fold rise in antibody titers measured by hemagglutination inhibition (HAI), microneutralization (MN), or neuraminidase inhibition (NAI) assays between sera collected at the postvaccination visit and those collected at the postseason visit. |
| Identify Serologic Correlates of Immune Protection. Suggest Changing to: Number of Participants Demonstrating Postvaccination Seroconversion. | Time between prevaccination and postvaccination, typically about 30 days. | Identify serologic correlates of immune protection. Seroconversion is defined as either prevaccination titer of less than 8 and postvaccination titer of greater than or equal to 32 or prevaccination titer of greater than or equal to 8 and greater than or equal to 4 fold rise in strain specific hemagglutination-inhibition (HAI) antibody titer between prevaccination and postvaccination sera. Data is shown separately for cases (subjects with symptomatic influenza A laboratory confirmed by isolation in cell culture or identification in real-time polymerase chain reaction (PCR) assay) and non-cases (subjects without cell culture, real time PCR or serologic evidence of influenza infection). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fluzone - Trivalent Inactivated Influenza Vaccine the trivalent inactivated influenza vaccine - Fluzone, manufactured by Sanofi-Pasteur | 814 |
| Flumist - Live-attenuated Influenza Vaccine live-attenuated influenza vaccine Flumist, manufactured by MedImmune | 813 |
| Placebo Physiologic saline administered as a nasal spray or intramuscular injection | 325 |
| Total | 1,952 |
Baseline characteristics
| Characteristic | Flumist - Live-attenuated Influenza Vaccine | Placebo | Fluzone - Trivalent Inactivated Influenza Vaccine | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 813 Participants | 325 Participants | 814 Participants | 1952 Participants |
| Age, Continuous | 23.5 years STANDARD_DEVIATION 7.7 | 22.9 years STANDARD_DEVIATION 6.7 | 23.2 years STANDARD_DEVIATION 7.4 | 23.3 years STANDARD_DEVIATION 7.4 |
| Region of Enrollment United States | 813 participants | 325 participants | 814 participants | 1952 participants |
| Sex: Female, Male Female | 519 Participants | 201 Participants | 494 Participants | 1214 Participants |
| Sex: Female, Male Male | 294 Participants | 124 Participants | 320 Participants | 738 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 814 | 0 / 813 | 0 / 325 |
| serious Total, serious adverse events | 8 / 814 | 4 / 813 | 3 / 325 |
Outcome results
Primary
Laboratory-confirmed (Culture and/or PCR) Symptomatic Influenza
Time frame: one influenza season - 2007-2008
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fluzone - Trivalent Inactivated Influenza Vaccine | Laboratory-confirmed (Culture and/or PCR) Symptomatic Influenza | 28 participants |
| Flumist - Live-attenuated Influenza Vaccine | Laboratory-confirmed (Culture and/or PCR) Symptomatic Influenza | 56 participants |
| Placebo | Laboratory-confirmed (Culture and/or PCR) Symptomatic Influenza | 35 participants |
Secondary
Identify Serologic Correlates of Immune Protection. Suggest Changing to: Number of Participants Demonstrating Postvaccination Seroconversion.
Identify serologic correlates of immune protection. Seroconversion is defined as either prevaccination titer of less than 8 and postvaccination titer of greater than or equal to 32 or prevaccination titer of greater than or equal to 8 and greater than or equal to 4 fold rise in strain specific hemagglutination-inhibition (HAI) antibody titer between prevaccination and postvaccination sera. Data is shown separately for cases (subjects with symptomatic influenza A laboratory confirmed by isolation in cell culture or identification in real-time polymerase chain reaction (PCR) assay) and non-cases (subjects without cell culture, real time PCR or serologic evidence of influenza infection).
Time frame: Time between prevaccination and postvaccination, typically about 30 days.
Population: Protocol only required that a subset of all specimens be run in order to get statistically significant outcomes; because the MN assay is labor intensive a subset of sera was processed in that assay for the Flumist-live attenuated influenza vaccine group to maintain comparable tested sample sizes among the three arms.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Fluzone - Trivalent Inactivated Influenza Vaccine | Identify Serologic Correlates of Immune Protection. Suggest Changing to: Number of Participants Demonstrating Postvaccination Seroconversion. | Cases | 20 Participants |
| Fluzone - Trivalent Inactivated Influenza Vaccine | Identify Serologic Correlates of Immune Protection. Suggest Changing to: Number of Participants Demonstrating Postvaccination Seroconversion. | Noncases | 178 Participants |
| Flumist - Live-attenuated Influenza Vaccine | Identify Serologic Correlates of Immune Protection. Suggest Changing to: Number of Participants Demonstrating Postvaccination Seroconversion. | Cases | 13 Participants |
| Flumist - Live-attenuated Influenza Vaccine | Identify Serologic Correlates of Immune Protection. Suggest Changing to: Number of Participants Demonstrating Postvaccination Seroconversion. | Noncases | 48 Participants |
| Placebo | Identify Serologic Correlates of Immune Protection. Suggest Changing to: Number of Participants Demonstrating Postvaccination Seroconversion. | Noncases | 3 Participants |
| Placebo | Identify Serologic Correlates of Immune Protection. Suggest Changing to: Number of Participants Demonstrating Postvaccination Seroconversion. | Cases | 0 Participants |
Secondary
Immune Response to Vaccination and Infection
Response was defined as greater than or equal to 4 fold rise in antibody titers measured by hemagglutination inhibition (HAI), microneutralization (MN), or neuraminidase inhibition (NAI) assays between sera collected at the postvaccination visit and those collected at the postseason visit.
Time frame: Postvaccination to postseason visit; typically about 3 months.
Population: Protocol only required that a subset of all specimens be run in order to get statistically significant outcomes; because the MN assay is labor intensive a subset of sera was processed in that assay for the Flumist-live attenuated influenza vaccine group to maintain comparable tested sample sizes among the three arms.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Fluzone - Trivalent Inactivated Influenza Vaccine | Immune Response to Vaccination and Infection | NAI assay | 9 Participants |
| Fluzone - Trivalent Inactivated Influenza Vaccine | Immune Response to Vaccination and Infection | HAI assay | 4 Participants |
| Fluzone - Trivalent Inactivated Influenza Vaccine | Immune Response to Vaccination and Infection | MN assay | 6 Participants |
| Flumist - Live-attenuated Influenza Vaccine | Immune Response to Vaccination and Infection | NAI assay | 33 Participants |
| Flumist - Live-attenuated Influenza Vaccine | Immune Response to Vaccination and Infection | HAI assay | 40 Participants |
| Flumist - Live-attenuated Influenza Vaccine | Immune Response to Vaccination and Infection | MN assay | 20 Participants |
| Placebo | Immune Response to Vaccination and Infection | HAI assay | 28 Participants |
| Placebo | Immune Response to Vaccination and Infection | MN assay | 26 Participants |
| Placebo | Immune Response to Vaccination and Infection | NAI assay | 22 Participants |
Secondary
Measure Immune Response Induced by the Vaccines and Identify Serologic Correlates of Immune Protection
Measure immune response induced by the vaccines. Response was defined as greater than or equal to 4 fold rise in antibody titers measured by hemagglutination inhibition (HAI), microneutralization (MN), or neuraminidase inhibition (NAI) assays between sera collected at the prevaccination visit and those collected at the postvaccination visit.
Time frame: Time between prevaccination visit and postvaccination visit; typically about 30 days.
Population: Protocol only required that a subset of all specimens be run in order to get statistically significant outcomes; because the MN assay is labor intensive a subset of sera was processed in that assay for the Flumist-live attenuated influenza vaccine group to maintain comparable tested sample sizes among the three arms.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Fluzone - Trivalent Inactivated Influenza Vaccine | Measure Immune Response Induced by the Vaccines and Identify Serologic Correlates of Immune Protection | NAI assay | 65 Participants |
| Fluzone - Trivalent Inactivated Influenza Vaccine | Measure Immune Response Induced by the Vaccines and Identify Serologic Correlates of Immune Protection | HAI assay | 137 Participants |
| Fluzone - Trivalent Inactivated Influenza Vaccine | Measure Immune Response Induced by the Vaccines and Identify Serologic Correlates of Immune Protection | MN assay | 35 Participants |
| Flumist - Live-attenuated Influenza Vaccine | Measure Immune Response Induced by the Vaccines and Identify Serologic Correlates of Immune Protection | NAI assay | 14 Participants |
| Flumist - Live-attenuated Influenza Vaccine | Measure Immune Response Induced by the Vaccines and Identify Serologic Correlates of Immune Protection | HAI assay | 48 Participants |
| Flumist - Live-attenuated Influenza Vaccine | Measure Immune Response Induced by the Vaccines and Identify Serologic Correlates of Immune Protection | MN assay | 10 Participants |
| Placebo | Measure Immune Response Induced by the Vaccines and Identify Serologic Correlates of Immune Protection | HAI assay | 92 Participants |
| Placebo | Measure Immune Response Induced by the Vaccines and Identify Serologic Correlates of Immune Protection | MN assay | 2 Participants |
| Placebo | Measure Immune Response Induced by the Vaccines and Identify Serologic Correlates of Immune Protection | NAI assay | 5 Participants |