Influenza
Conditions
Keywords
antiviral drugs, influenza vaccines
Brief summary
This unblinded pilot study is intended to assess the feasibility of a larger double-blind, randomized control trial. For the larger trial the investigators are interested in understanding the relative benefits of vaccine and antiviral prophylaxis, the risk factors for influenza infection in healthy adults, and in assessing the safety and tolerability of seasonal antiviral prophylaxis in healthcare workers. The pilot study will be assessing the rate of infection with influenza and the rate of adherence to long-term zanamivir in 60 healthy volunteers.
Detailed description
Several studies have demonstrated that zanamivir and oseltamivir are effective in preventing influenza infection and illness when used either as prophylaxis after exposure to a household contact with influenza or when taken for several weeks at the height of influenza activity in the general community. However, the longest duration of prophylaxis with neuraminidase inhibitors in two clinical trials, to date, has been six weeks. Antiviral medication will likely have an important role in the response to the next influenza pandemic. Additionally, there may be indications for use during seasons when the major infecting strain of influenza in not one whose antigen is well covered by the vaccine.
Interventions
Sponsors
GlaxoSmithKline
Mount Sinai Hospital, Canada
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 69 Years
Healthy volunteers
Yes
Inclusion criteria
* 18-69 years old as of 01/Nov/2008 * have an understanding of the study, agree to its provisions, and give written informed consent prior to study entry * available for follow-up during the study period * if a women of child-bearing years, must meet criteria to prevent pregnancy
Exclusion criteria
* allergy to any component of influenza vaccine or zanamivir * previous serious adverse event associated with influenza vaccination * receipt of influenza vaccine between 01/Mar/2008 and start of study * previous adverse event associated with the use of antiviral medications * expecting to be unable to take zanamivir for more than 72 hours during study period * planning to spend more than 2 consecutive weeks outside Canada or more than 100 km from the study site during study period * pregnant, or planning to become pregnant, during study period * breastfeeding, or planning to breastfeed, a child under 12 months of age during study period * receipt of immunoglobulin within six months of study entry * immunocompromising condition or therapy that would be expected to reduce the efficacy of vaccination * plans to receive cytotoxic or radiation therapy during study period * history of cardiovascular or pulmonary disease that has required hospital admission within the past year * history of asthma or other chronic respiratory disease * participating in a trial that will result in the receipt of an investigational medication during the period that zanamivir may be taken (15/Nov/2008 to 30/Apr/2009)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Laboratory Confirmed Influenza Infections | 6 months | Four-fold increase in antibody titer 2 weeks post injection and end of study or positive laboratory test for influenza during study (polymerase chain reaction \[PCR\] or culture) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Adhering to Long-term Zanamivir Prophylaxis | 5 months | Number of subjects taking 80% or more doses per week of zanamivir (10 mg once daily), as influenza prophylaxis, for 13 weeks or longer (as measured by weekly diary and dose counts at study visits). |
Countries
Canada
Participant flow
Recruitment details
Recruitment period: November 5th to November 19th, 2008 in Toronto, Ontario Canada. Most subjects were healthcare workers employed at a 470-bed acute care facility.
Participants by arm
| Arm | Count |
|---|---|
| Influenza Vaccine Influenza vaccine, using Fluviral trivalent split virus vaccine | 22 |
| Antiviral Prophylaxis Zanamivir, 10mg once daily during period of influenza activity, as prophylaxis | 42 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | Antiviral Prophylaxis | Influenza Vaccine | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 42 Participants | 22 Participants | 64 Participants |
| Age, Continuous | 40 years STANDARD_DEVIATION 10 | 40 years STANDARD_DEVIATION 10 | 40 years STANDARD_DEVIATION 10 |
| Region of Enrollment Canada | 42 participants | 22 participants | 64 participants |
| Sex: Female, Male Female | 27 Participants | 17 Participants | 44 Participants |
| Sex: Female, Male Male | 15 Participants | 5 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 22 | 0 / 40 |
| serious Total, serious adverse events | 2 / 20 | 1 / 40 |
Outcome results
Primary
Number of Laboratory Confirmed Influenza Infections
Four-fold increase in antibody titer 2 weeks post injection and end of study or positive laboratory test for influenza during study (polymerase chain reaction \[PCR\] or culture)
Time frame: 6 months
Population: intention to treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Influenza Vaccine | Number of Laboratory Confirmed Influenza Infections | 2 infections |
| Antiviral Prophylaxis | Number of Laboratory Confirmed Influenza Infections | 1 infections |
Comparison: That in a year with mismatch between influenza vaccine antigen and infecting H3N2 strain, seasonal (10-13 weeks) antiviral prophylaxis in adults will provide better protection from symptomatic influenza infection than trivalent inactivated split virus influenza vaccine.p-value: 0.2595% CI: [0.01, 4.8]Fisher Exact
Secondary
Number of Subjects Adhering to Long-term Zanamivir Prophylaxis
Number of subjects taking 80% or more doses per week of zanamivir (10 mg once daily), as influenza prophylaxis, for 13 weeks or longer (as measured by weekly diary and dose counts at study visits).
Time frame: 5 months
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Antiviral Prophylaxis | Number of Subjects Adhering to Long-term Zanamivir Prophylaxis | 34 participants |