Safe Administration of Flu Vaccine to Egg Allergic Children

NCT01264601 | Completed Results DMC

• 1 other identifier: HUM 00038826
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 5

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.

Conditions

Egg Allergy

Keywords

Anaphylaxis to Egg; Severe Egg Allergy

Outcome Measures

Primary Outcomes (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.

  48 hours

Secondary Outcomes (1)

• Influence of Atopic Co-morbidities on Severe Reactivity to Vaccine as it Was Administered

  6 months

Study Arms (2)

Single Dose

EXPERIMENTAL

This 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.

Biological: Trivalent Influenza Vaccine

Graded Challenge

EXPERIMENTAL

Subjects 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.

Biological: Trivalent Influenza Vaccine

Interventions

Trivalent Influenza Vaccine BIOLOGICAL

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

Graded Challenge; Single Dose

Eligibility Criteria

• Age: 6 Months - 24 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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).
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Michigan: lead
• American College of Allergy, Asthma and Immunology: collaborator

Study Sites (5)

Scripps Clinic

San Diego, California, 92130, United States

Location

University of Michigan Health Systems

Ann Arbor, Michigan, 48106, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

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

Pittsburgh, Pennsylvania, 15224, United States

Location

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

Dallas, Texas, 75235, United States

Location

Related Publications (13)

• 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.

  BACKGROUND

• 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.

  BACKGROUND

• 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.

  PMID: 21055666 BACKGROUND

• 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.

  PMID: 20579720 BACKGROUND

• 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.

  PMID: 16461139 BACKGROUND

• 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.

  PMID: 20368312 BACKGROUND

• 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.

  PMID: 20451987 BACKGROUND

• 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.

  PMID: 20060576 BACKGROUND

• 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.

  PMID: 9821418 BACKGROUND

• 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.

  PMID: 12464947 BACKGROUND

• 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.

  PMID: 20226505 BACKGROUND

• 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.

  PMID: 21195939 BACKGROUND

• 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.

  PMID: 21459425 BACKGROUND

MeSH Terms

Conditions

Egg Hypersensitivity

Interventions

Influenza Vaccines

Condition Hierarchy (Ancestors)

Food Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Matthew Greenhawt, MD, MBA
• Organization: University of Michigan

mgreenha@umich.edu

734/936-5634

Study Officials

• Matthew Greenhawt, MD, MBA

  University of Michigan

  PRINCIPAL INVESTIGATOR

• Georgiana Sanders, MD, MS

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: December 21, 2010
• First Posted: December 22, 2010
• Study Start: October 1, 2010
• Primary Completion: May 1, 2012
• Study Completion: August 1, 2012
• Last Updated: October 26, 2017
• Results First Posted: October 26, 2017

Record last verified: 2017-09

Locations

US (5)