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Egg AllergySAFENCT01264601

Safe Administration of Flu Vaccine to Egg Allergic Children

A study testing Trivalent Influenza Vaccine in people with Egg Allergy, run by University of Michigan at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 6 months to 24 years
Conditions the study is for
Egg Allergy
What is being tested?
Trivalent Influenza Vaccine
Type of treatment
Vaccines
Could I receive a placebo?
No, everyone receives an active treatment
How many people
31 participants
Where
5 sitesUnited States
Study dates
Oct 2010to Aug 2012
Phase
Interventional
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 6 months to 24 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Ages 6 months-24 years, seen in the UMHS Allergy Clinics (and similar academic Allergy clinics of collaborating sites) in the last 24 months with a discharge diagnosis code of v15.03 indicating an of egg allergy, AND with correlated history including the following:
  • Egg allergy as defined by:
  • Positive egg challenge; OR strong history suggestive of clinical allergy within 4 hours of ingestion AND egg-specific IgE above 0.70 kUA/L OR wheal 3mm > control (or 2+ score if wheal size not available).
  • Anaphylaxis after egg ingestion, defined by:
  • Patients with a verified history (by chart review) of their single most severe reaction to egg resulting in the following, per NIAID/FAAN 2006 criteria:5 i) Acute onset of an illness with involvement of the skin/mucosal tissue (e.g., generalized hives, pruritus or flushing, swollen lips-tongue-uvula) AND EITHER respiratory compromise (e.g., dyspnea, wheezing/bronchospasm, stridor, reduced peek expiratory flow) OR reduced blood pressure or associated symptoms (eg, hypotonia or syncope); OR ii) Two or more of the following after exposure to an allergen: involvement of the skin/mucosal tissue (e.g., urticaria, itching/flushing, swollen lips/tongue/uvula); respiratory compromise (e.g., dyspnea, wheezing/bronchospasm, stridor, reduced peak expiratory flow); reduced blood pressure or associated symptoms (e.g., hypotonia or syncope); or persistent gastrointestinal symptoms (e.g., crampy abdominal pain or vomiting); OR iii) Hypotension after exposure to known allergen for that patient c) A severe allergic reaction will be defined by a history of development of severe hives, angioedema, or allergic asthma attributable to egg allergy.
  • Subject must fulfill criteria for both egg allergy and for either anaphylaxis or a severe allergic reaction (both attributable to egg) to be included in the study, i.e. both (a) and either (b) or (c).
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  • Ability to remain off antihistamines for at least 5 days prior to the study visit, for skin testing.
  • For children, the ability to remain in the exam room for the duration of the testing visit.
  • Previous history of TIV of H1N1 vaccination is neither inclusive nor exclusive for the study.

Who cannot join

  • Does not fulfill requirements for both egg allergy AND anaphylaxis or severe allergic reaction.
  • Prolonged use of immunosuppressive medication, including high dose corticosteroids > 6 months, as well as other immunosuppressive agents.
  • Prior history of egg allergy, now outgrown and tolerating egg ingestion.
  • Eosinophilic esophagitis.
  • Cardiac disease.
  • Known malignancy under treatment.
  • Pregnant women.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites
  • University of Michigan Health Systems

    Ann Arbor, Michigan, 48106

  • Children's Medical Center Dallas, University of Texas-Southwestern Medical Center

    Dallas, Texas, 75235

  • Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center

    Pittsburgh, Pennsylvania, 15224

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Scripps Clinic

    San Diego, California, 92130

Other trials in United States

About this study

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

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.

Read the 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

Conditions
Egg Allergy
Being tested
Trivalent Influenza Vaccine
Keywords
Anaphylaxis to Egg, Severe Egg Allergy
Medical subject headings
Egg Hypersensitivity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Trivalent Influenza VaccineBiological

    Age appropriate dose of seasonal Trivalent Influenza Vaccine (TIV), either 0.25mL under age 3 or 0.5mL over the age of 3.

Study groups in NCT01264601
Study groupRoleWhat they receive
Single DoseExperimentalThis arm will receive TIV as 2 doses, the first of which will be normal saline administered at approximately 10% of the total age appropriate dose volume, followed 30 minutes later by the full age appropriate dose. For children receiving a 0.25ml dose, a 20%/80% split will be used for ease of administration in drawing up the dose.
Receives: Biological: Trivalent Influenza Vaccine
Graded ChallengeExperimentalSubjects in this arm will receive TIV by standard 10%/90% 2-step graded challenge split of the age appropriate dose, separated by 30 minutes. For children receiving a 0.25ml dose, a 20%/80% split will be used for ease of administration in drawing up the dose.
Receives: Biological: Trivalent Influenza Vaccine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Categorical Reactivity to Vaccine as it Was Administered

    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. All parties will report any adverse reactions occurring in the next 48 hours after vaccination that were not observed at the time of in office observation.

    Measured: 48 hours

Secondary outcomes (1)
  1. Influence of Atopic Co-morbidities on Severe Reactivity to Vaccine as it Was Administered

    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.

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Dec 2010 (estimated)
  2. Study startOct 2010
  3. Primary completionMay 2012
  4. Study completionAug 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
31 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01264601
Sponsor's protocol ID
HUM 00038826
Acronym
SAFE
Status last verified
Sep 2017
First submitted
21 Dec 2010
Last updated
26 Oct 2017
Data monitoring committee
Yes

Publications

  • American Academy of Pediatrics. Influenza. In: Pickering LK, ed. Red Book: 2009 Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009:400-412. Available at: http://aapredbook.aappublications.org/cgi/content/full/2009/1/3.64. Accessed June 18, 2010.

  • Howe LE, Chernin A, Sanders GM. Administration of Influenza Vaccine to the Egg Allergic Child Under 36 Months (Abstract). J Allergy Clin Immunol 2010; 125:AB23.

  • Greenhawt MJ, Chernin AS, Howe L, Li JT, Sanders G. The safety of the H1N1 influenza A vaccine in egg allergic individuals. Ann Allergy Asthma Immunol. 2010 Nov;105(5):387-93. doi: 10.1016/j.anai.2010.08.015.

    PubMed 21055666
  • Gagnon R, Primeau MN, Des Roches A, Lemire C, Kagan R, Carr S, Ouakki M, Benoit M, De Serres G; PHAC-CIHR Influenza Research Network. Safe vaccination of patients with egg allergy with an adjuvanted pandemic H1N1 vaccine. J Allergy Clin Immunol. 2010 Aug;126(2):317-23. doi: 10.1016/j.jaci.2010.05.037. Epub 2010 Jun 25.

    PubMed 20579720
  • Sampson HA, Munoz-Furlong A, Campbell RL, Adkinson NF Jr, Bock SA, Branum A, Brown SG, Camargo CA Jr, Cydulka R, Galli SJ, Gidudu J, Gruchalla RS, Harlor AD Jr, Hepner DL, Lewis LM, Lieberman PL, Metcalfe DD, O'Connor R, Muraro A, Rudman A, Schmitt C, Scherrer D, Simons FE, Thomas S, Wood JP, Decker WW. Second symposium on the definition and management of anaphylaxis: summary report--Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J Allergy Clin Immunol. 2006 Feb;117(2):391-7. doi: 10.1016/j.jaci.2005.12.1303.

    PubMed 16461139
  • Chung EY, Huang L, Schneider L. Safety of influenza vaccine administration in egg-allergic patients. Pediatrics. 2010 May;125(5):e1024-30. doi: 10.1542/peds.2009-2512. Epub 2010 Apr 5.

    PubMed 20368312
  • Li JT, Rank MA, Squillace DL, Kita H. Ovalbumin content of influenza vaccines. J Allergy Clin Immunol. 2010 Jun;125(6):1412-3; author reply 1413-4. doi: 10.1016/j.jaci.2010.03.009. Epub 2010 May 7. No abstract available.

    PubMed 20451987
  • Waibel KH, Gomez R. Ovalbumin content in 2009 to 2010 seasonal and H1N1 monovalent influenza vaccines. J Allergy Clin Immunol. 2010 Mar;125(3):749-51, 751.e1. doi: 10.1016/j.jaci.2009.12.015. Epub 2010 Jan 8. No abstract available.

    PubMed 20060576
  • James JM, Zeiger RS, Lester MR, Fasano MB, Gern JE, Mansfield LE, Schwartz HJ, Sampson HA, Windom HH, Machtinger SB, Lensing S. Safe administration of influenza vaccine to patients with egg allergy. J Pediatr. 1998 Nov;133(5):624-8. doi: 10.1016/s0022-3476(98)70101-5.

    PubMed 9821418
  • Zeiger RS. Current issues with influenza vaccination in egg allergy. J Allergy Clin Immunol. 2002 Dec;110(6):834-40. doi: 10.1067/mai.2002.129372.

    PubMed 12464947
  • Kelso JM. Administration of influenza vaccines to patients with egg allergy. J Allergy Clin Immunol. 2010 Apr;125(4):800-2. doi: 10.1016/j.jaci.2010.02.013. Epub 2010 Mar 11. No abstract available.

    PubMed 20226505
  • Greenhawt MJ, Li JT, Bernstein DI, Blessing-Moore J, Cox L, Khan D, Lang DM, Nicklas RA, Oppenheimer J, Portnoy JM, Randolph C, Schuller DE, Spector SL, Tilles SA, Wallace D. Administering influenza vaccine to egg allergic recipients: a focused practice parameter update. Ann Allergy Asthma Immunol. 2011 Jan;106(1):11-6. doi: 10.1016/j.anai.2010.11.015. No abstract available.

    PubMed 21195939
  • Webb L, Petersen M, Boden S, LaBelle V, Bird JA, Howell D, Burks AW, Laubach S. Single-dose influenza vaccination of patients with egg allergy in a multicenter study. J Allergy Clin Immunol. 2011 Jul;128(1):218-9. doi: 10.1016/j.jaci.2011.02.013. Epub 2011 Apr 2. No abstract available.

    PubMed 21459425

Questions about this trial

What is this clinical trial studying?

A study testing Trivalent Influenza Vaccine in people with Egg Allergy, run by University of Michigan at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Oct 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Categorical Reactivity to Vaccine as it Was Administered (time frame: 48 hours). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01264601, which also lists 13 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2017.

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