Clinical trial NCT01368796: Comparison of 4 Influenza Vaccines in Seniors
Official title: Controlled Comparison in Canadian Seniors of Seasonal Influenza Vaccines for 2011-2012
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Influenza Vaccine
Keywords: Vaccine
Influenza vaccine
Adjuvanted Influenza vaccine
Intradermal Influenza vaccine
Seniors
Acceptability of vaccines
Influenza
Lead sponsor: University of British Columbia
Sponsor class: OTHER
Collaborators: name: PHAC/CIHR Influenza Research Network
First posted: 2011-06-08
Enrollment: 953
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Based on information from several years of looking at Influenza vaccination doctors know that:

* Older adults suffer the worst illness and most deaths caused by Influenza illness of all age groups.
* Older adults do not seem to get as good a level of protection as younger adults after getting the usual seasonal Influenza vaccine.

Because of this information doctors wonder if one of the new seasonal Influenza vaccines is more effective or more acceptable.

This study has been designed to answer some of these questions. On this study doctors will compare 2 new vaccines against the usual seasonal influenza vaccine for protectiveness using several different testing methods (including the usual tests) and for acceptability.

Detailed description: This study is prospective, multicenter, randomized, evaluator-blinded, controlled, parallel group study of 3 licensed seasonal influenza vaccine products conducted in seniors, with a 4th vaccine included in a substudy of cellular immune responses.

Ambulatory adults 65+ years of age, in good health or with stable health conditions, given TIV within the past 2 years, will be recruited in multiple Canadian centres. Subjects can be dwelling in the community or in centers providing minimal assisted living support. A total of 930 subjects will be enrolled.

Subjects will be centrally (electronically) randomized to receive either TIV, IDV or AIV on Day 0. Three blood samples will be collected (1 pre and 2 post vaccination) to measure HAI antibody responses to each virus strain (H1N1, H3N2 and B) in each vaccine, using standardized assays. Randomly selected subsets of sera from each study group will also be tested for neutralizing antibody and for cross-protection against drift variants of H3N2, H1N1 and B viruses. In a subset of subjects in Vancouver, randomization assignments will include TIV2 and extra blood samples will be obtained 0, 21 and 72 days post vaccination for CMI testing. Safety assessments will be conducted on Day 7, Day 21 and Day 180 following vaccination. Acceptability of each product, reflecting the frequency, severity and tolerability of adverse effects, will be assessed.

Eligibility criteria: Inclusion Criteria:

* Written informed consent provided by the subject, who can be male or female
* Subjects who the investigator believes can and will comply with the requirements of the protocol (i.e. return for follow-up visits, record safety observations and able to converse with study personnel including by personal telephone)
* Age 65 years or older at Visit 1
* Generally good health (stable chronic conditions acceptable), living independently or with minimal assistance (Clinical Frailty score 1-5) (33) and able to attend clinic appointments
* Receipt of at least one dose of TIV within the previous 2 influenza seasons, documented by written record or attested by a confident personal recollection. This refers to the trivalent seasonal vaccine, not the H1N12009 pandemic vaccine.

Exclusion Criteria:

* receipt of non-study influenza vaccine for 2011-12
* receipt of any live vaccine within 4 weeks or inactivated vaccine within one week of Visit 1 or planned administration of any non-study vaccines between Visits 1 and 2
* systemic hypersensitivity to influenza vaccine, hen's eggs or other vaccine constituent (eg neomycin sulphate, kanamycin, formalin)
* severe reaction to any previous influenza vaccine or vaccine component
* bleeding disorder, including anticoagulant therapy or thrombocytopenia, that contraindicates IM injection or blood collection (does not include daily low-dose ASA).
* incapacity to provide fully informed consent or be attentive to follow-up observations, resulting from cognitive impairment, abuse of alcohol, drug addiction
* lack of telephone access, inadequate fluency in English (or French in applicable jurisdictions), uncertain availability during the 3 week study participation period or for the 6 month follow-up visit
* immune compromise resulting from disease or immunosuppressive systemic medication use within 3 months of V1
* receipt of blood or blood product within 3 months of V1
* unstable medical condition, as indicated by a requirement for hospitalization or a substantial medication change to stabilize said condition within previous 3 months
* Clinical Frailty score of 6-7 (moderately frail or severely frail)
* history of Guillain-Barré syndrome

Primary outcomes:
measure: HAI response
timeFrame: Day 0; Day 21; Day 180
Secondary outcomes:
measure: Seroprotection rates using microneutralization titres and cytokine testing
timeFrame: Day 0; Day 21; and Day 70
measure: Safety and Acceptability
timeFrame: Days 0-6; Day 21; Day 70; and Day 180
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: University of British Columbia, VITALiTY Research Center
state: British Columbia
city: Winnipeg
country: Canada
facility: University of Manitoba, Department of Medicine
state: Manitoba
city: Halifax
country: Canada
facility: Canadian Centre for Vaccinology Dalhousie University
state: Nova Scotia
city: Hamilton
country: Canada
facility: McMaster University
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital Research Institute, University of Ottawa
state: Ontario
city: Toronto
country: Canada
facility: University of Toronto, Mt Sinai Hospital
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Center - Vaccine Study Center
state: Quebec
city: Quebec City
country: Canada
facility: Unité de Recherche en Santé Publique (CHUQ),
state: Quebec
Study officials:
affiliation: University of Britich Columbia
name: David W Scheifele, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Skowronski DM, Janjua NZ, De Serres G, Purych D, Gilca V, Scheifele DW, Dionne M, Sabaiduc S, Gardy JL, Li G, Bastien N, Petric M, Boivin G, Li Y. Cross-reactive and vaccine-induced antibody to an emerging swine-origin variant of influenza A virus subtype H3N2 (H3N2v). J Infect Dis. 2012 Dec 15;206(12):1852-61. doi: 10.1093/infdis/jis500. Epub 2012 Aug 7.