Safe Administration of Flu Vaccine to Egg Allergic Children
Condition: Egg Allergy
MeSH terms: Hypersensitivity; Egg Hypersensitivity
Study type: Interventional

Summary: 
      Historically, providing influenza vaccination of egg allergic children and young adults (EAC)
      with a history of anaphylaxis to egg, or other severe symptoms of an allergic reaction to egg
      (e.g., severe hives, swelling, or asthma), has been contra-indicated, though vaccination of
      children with less severe egg allergy has been shown to be safe. Though many children with
      severe egg allergy, including anaphylaxis, have received past influenza vaccination
      anecdotally, very few data exist to show this procedure is safe. The investigators propose a
      double blind, placebo-controlled randomized, prospective multi-centered study to a)
      demonstrate seasonal trivalent influenza vaccine (TIV) can be safely given in a single dose
      (as opposed to through 2-step graded dosing of 10% then 90% of the vaccine dose) to EAC
      despite history of anaphylaxis or previous severe allergic reaction to egg; and b) provide
      further evidence that adverse outcomes are not related to ovalbumin (egg) content in TIV.

      Study participants must have a documented history of a severe egg allergy, substantiated by
      both a history of clinical reactivity AND either a positive skin test or ImmunoCAP/RAST test
      greater than 0.7 kUA/L. Participants will be randomized to receive either a 2-step graded
      challenge or a single dose given after a small placebo dose of saline (to mimic the graded
      challenge). If required, all participants will receive a booster vaccination as a single
      dose.
    

Detailed description: 
      Seasonal Trivalent Influenza Vaccine (TIV) is grown in embryonated chicken eggs, and since it
      contains residual egg protein (ovalbumin), providing TIV to egg allergic children (EAC) could
      potentially provoke allergic reactivity. Because of this possibility, historically caution
      has been advised in providing TIV to these children, and the vaccine has been withheld in
      certain individuals, though for many it has been safely administered after vaccine skin
      testing and stepwise administration. In the 2009 American Academy of Pediatrics Red Book (and
      previous editions), a history of severe allergic reactivity to egg is a contraindication to
      receiving TIV, though it is acknowledged that less severely egg allergic kids have safely
      received TIV if precautions had been taken.

      In the past year, several studies have emerged that demonstrate that most, if not all, EAC
      can safely be vaccinated with both TIV ad the H1N1 vaccine. A recent 5 year review of TIV
      administration in EAC ages 6 mo-36 mo, showed safe administration to 135 EAC after TIV skin
      testing, including 14 subjects with a history of anaphylaxis to egg. Another large,
      retrospective study of non-anaphylactic EAC showed TIV could be successfully administered
      using a 2-step protocol without skin testing to TIV. In a single center H1N1 vaccine study
      last fall, 105 EAC received either a full vaccine dose if skin tests were negative, or a
      2-step graded challenge if the tests were positive, including 25 subjects with a history of
      anaphylaxis. No allergic reactions resulted, regardless of the results of skin testing, the
      method of administration, ovalbumin content of the vaccine, or use of a different booster lot
      without pre-testing. In a sister-study, 68 H1N1 participants prospectively received TIV
      safely without graded challenge, including 13 EAC with a history of egg anaphylaxis. A large
      prospective, Canadian multi-centered study, using an adjuvanted H1N1 preparation containing
      0.03μg/mL of ovalbumin, was safely given to 72 individuals with either a history of severe
      cardiopulmonary reactivity to egg or a history of poorly controlled asthma (this group was
      not further broken down), via 2-step graded challenge. Thus, these studies suggest it is safe
      for EAC with a history of anaphylaxis to receive TIV and H1N1 without pre-testing, suggest
      that use of a 2-step graded challenge may be unnecessary, and show some evidence that past
      egg allergy severity may not be an important factor in vaccine tolerance. Recent guidelines
      published by the AAAAI suggest a flexible approach is reasonable, and that EAC can receive
      TIV without prior skin testing through either a single dose or a 2-step approach.

      This double blind, randomized, placebo-controlled, multi-centered study aims to investigate
      the safety of TIV given to EAC with a history of a severe past reaction or anaphylaxis to
      egg, and aims to show that a single dose route of administration is safe and sufficient.
      Participants with new or established severe egg allergy (see eligibility criteria) will be
      randomized to receive either a 2-step (10%, followed by 30 min. observation, then residual
      90%) graded challenge or a single dose of TIV given 30 minutes after a placebo dose of normal
      saline is administered (to approximate the graded challenge). Vaccine tolerance will be
      analyzed and compared to ovalbumin content of the vaccine lots, as well as to baseline
      characteristics of the participant's egg allergy and allergic history.

      Secondary outcomes originally posted on the www.clinicaltrials.gov website were hypotheses
      which were aims of complex data analysis but were not in and of themselves actual outcome
      measures. Therefore these have been deleted from the record
    

Intervention name(s): Trivalent Influenza Vaccine
Intervention type(s): Biological
Intervention description(s): Age appropriate dose of seasonal Trivalent Influenza Vaccine (TIV), either 0.25mL under age 3 or 0.5mL over the age of 3.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Anaphylaxis to Egg; Severe Egg Allergy