Clinical Trial: Safe Administration of Flu Vaccine to Egg Allergic Children

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Multi-Centered, Randomized, Placebo-Controlled Trial of the Safety of Influenza Vaccine in Egg Allergic Children With a History of Anaphylaxis or Severe Allergy to Egg

Brief 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 Summary:

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 stud
Sponsor: University of Michigan

Current Primary Outcome: Demonstrate that egg allergic individuals with a history of anaphylaxis or severe reaction to egg can safely receive a single dose of TIV (Trivalent Influenza Vaccine) [ Time Frame: 6-24 months ]

After randomization, group 1 will receive a 10%/90% (or 20%/80% for 0.25ml) graded challenge of the age appropriate TIV dose, separated by 30 minutes for observation. Group 2 will receive a first dose consisting of normal saline at a volume equal to 10% of their age appropriate dose, and the second dose will consist of their full age appropriate dose as the "90%" equivalent, also separated by 30 minutes of observation. For children receiving a 0.25ml dose, a 20%/80% split will be used for ease of administration in drawing up the dose.


Original Primary Outcome: Demonstate that egg allergic individuals with a history of anaphylaxis or severe reaction to egg can safely receive a single dose of TIV (Trivalent Influenza Vaccine) [ Time Frame: 6 months ]

Subjects will be randomized at the time of enrollment to receive their vaccine as a 2-step process. 1 group will receive a 10%/90% graded challenge of the age appropriate TIV dose, separated by 30 minutes for observation. The second group will receive 2 doses as well, but the first dose will consist of normal saline at a volume equal to 10% of their age appropriate dose, and the second dose will consist of their full age appropriate dose as the "90%" equivalent. All doses will be separated by 30 minutes of observation for symptom development by an individual blinded to the study arm.


Current Secondary Outcome:

  • Egg allergic individuals with a history of anaphylaxis or severe allergic reactivity to egg will tolerate the influenza vaccine without a greater risk of serious reactions than the general public. [ Time Frame: 6 months ]
    Rates of reaction will be compared to rates reported in the VAERS system for severe reactions
  • Severity of atopic co-morbidities is not a significant factor in the development of local or systemic allergic reactions in receiving TIV. [ Time Frame: 6 months ]
    Rates of co-morbid allergic disease, size and magnitude of egg skin and ImmunoCAP tests, presence of other food allergy, and tolerance of "baked egg" will be assessed through a screening questionnaire and chart review, and compared between the groups to assess for any significant differences that may predict TIV tolerance.


Original Secondary Outcome:

  • Egg allergic individuals with a history of anaphylaxis or severe allergic reactivity to egg will tolerate the influenza vaccine without a greater risk of serious reactions than the general public. [ Time Frame: 6 months ]
    Rates of reaction will be compared to rates reported in the VAERS system for severe reactions
  • Vaccine ovalbumin content is not a factor in the development of significant allergic reactions in egg allergic children. [ Time Frame: 6 months ]
    TIV lots used in this study will be analyzed for ovalbumin content by a ELISA based assay. These levels per lot will then be compared to rates of reactions reported to specific vaccine lots.
  • Severity of atopic co-morbidities is not a significant factor in the development of local or systemic allergic reactions in receiving TIV. [ Time Frame: 6 months ]
    Rates of co-morbid allergic disease, size and magnitude of egg skin and ImmunoCAP tests, presence of other food allergy, and tolerance of "baked egg" will be assessed through a screening questionnaire and chart review, and compared between the groups to assess for any significant differences that may predict TIV tolerance.


Information By: University of Michigan

Dates:
Date Received: December 21, 2010
Date Started: October 2010
Date Completion:
Last Updated: June 6, 2013
Last Verified: June 2013