Comparison of 4 Influenza Vaccines in Seniors - Full Text View

Purpose

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.

Condition	Intervention	Phase
Influenza Vaccine	Biological: Agriflu Biological: Fluad Biological: Intanza Biological: Vaxigrip	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Prevention
Official Title:	Controlled Comparison in Canadian Seniors of Seasonal Influenza Vaccines for 2011-2012

Resource links provided by NLM:

MedlinePlus related topics: Flu

Drug Information available for: Influenza Vaccines

U.S. FDA Resources

Further study details as provided by University of British Columbia:

Primary Outcome Measures:

HAI response [ Time Frame: Day 0; Day 21; Day 180 ] [ Designated as safety issue: No ]
The primary outcome measures will be the 3-week post-vaccination immune (HAI) responses to the 3 vaccine strains present in each product, assessed by the EMEA/CHMP criteria for evaluation of immune responses to influenza vaccines in persons >60 years of age.

Secondary Outcome Measures:

Seroprotection rates using microneutralization titres and cytokine testing [ Time Frame: Day 0; Day 21; and Day 70 ] [ Designated as safety issue: No ]
As secondary immunologic outcomes seroprotection rates will be compared between the products using a higher titer (≥160) as threshold. Microneutralization titers will be compared among products at the 3 sampling points, using sera from 100 subjects per group. Cross-protection afforded by each vaccine against drift variants of H3N2, H1N1 and B viruses will be assessed using serum panels selected from 50 subjects in each group. Cellular immune responses elicited will be compared in subgroups of 30 subjects per vaccine in the CMI subjset.
Safety and Acceptability [ Time Frame: Days 0-6; Day 21; Day 70; and Day 180 ] [ Designated as safety issue: Yes ]
Safety and acceptability of the vaccines will also be examined and compared as the safety outcomes. The primary outcome measurements will be the rates of local adverse events (pain, redness, swelling, itchiness) as rates of general adverse events are not expected to differ substantially among the products.

Estimated Enrollment:	930
Study Start Date:	July 2011
Estimated Study Completion Date:	April 2012
Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Trivalent Influenza vaccine subunit The seasonal vaccine (Agriflu, Novartis) contains egg-derived, inactivated and detergent split versions of the 3 influenza strains (tri-valent). It is given into the muscle of the upper arm at a dose of 0.5 mL.	Biological: Agriflu 0.5mL dose IM vaccination
Active Comparator: Adjuvanted Tri-valent Influenza Vaccine The adjuvanted vaccine (Fluad, Novartis) is made with an immune-stimulator (MF59) that contains squalene oil microdroplets and two surfactants, Tween 80 and Span 65. It is given into the muscle of the upper arm at a dose of 0.5 mL.	Biological: Fluad 0.5mL dose of vaccine given IM
Active Comparator: Intradermal Tri-valent Influenza vaccine (Intanza 15ug, Sanofi Pasteur) is an inactivated, split-virion influenza vaccine. Strains are grown in fertilized hen's eggs, inactivated with formalin and split using Triton X-100 detergent, as for TIV. The syringe is attached to a micro-needle injection system (Beckton Dickinson) that limits the depth of injection to just under the skin. It is given into the skin over the upper arm at a dose of 0.1 mL.	Biological: Intanza 0.5mL dose vaccine given IM
Active Comparator: Trivalent Split-virion Influenza vaccine Vaxigrip, Sanofi Pasteur is an inactivated, split-virion Influenza vaccine. The 3 influenza strains are grown on fertilized eggs, concentrated, purified in a sugar-like solution, detergent split, and inactivated by formaldehyde, then diluted in phosphate buffered salt solution. A dose of 0.5 mL is given into the muscle of the arm.	Biological: Vaxigrip 0.5mL dose vaccine given IM

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

Ages Eligible for Study:	65 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01368796

Locations

Canada, British Columbia
University of British Columbia, VITALiTY Research Center
Vancouver, British Columbia, Canada
Canada, Manitoba
University of Manitoba, Department of Medicine
Winnipeg, Manitoba, Canada
Canada, Nova Scotia
Canadian Centre for Vaccinology Dalhousie University
Halifax, Nova Scotia, Canada
Canada, Ontario
McMaster University
Hamilton, Ontario, Canada
The Ottawa Hospital Research Institute, University of Ottawa
Ottawa, Ontario, Canada
University of Toronto, Mt Sinai Hospital
Toronto, Ontario, Canada
Canada, Quebec
McGill University Health Center - Vaccine Study Center
Montreal, Quebec, Canada
Unité de Recherche en Santé Publique (CHUQ),
Quebec City, Quebec, Canada

Sponsors and Collaborators

University of British Columbia

PHAC/CIHR Influenza Research Network

Investigators

Principal Investigator:

David W Scheifele, MD

University of Britich Columbia

More Information

No publications provided by University of British Columbia

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Responsible Party:	University of British Columbia
ClinicalTrials.gov Identifier:	NCT01368796 History of Changes
Other Study ID Numbers:	H11-01457, PCIRN RT09
Study First Received:	June 6, 2011
Last Updated:	March 9, 2012
Health Authority:	Canada: Health Canada

Keywords provided by University of British Columbia:

Vaccine
Influenza vaccine
Adjuvanted Influenza vaccine

Intradermal Influenza vaccine
Seniors
Acceptability of vaccines

Additional relevant MeSH terms:

Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections

Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on June 18, 2013

Comparison of 4 Influenza Vaccines in Seniors (RT09)