An interventional study of Trivalent Influenza Vaccine in Egg Allergy, sponsored by University of Michigan. Completed at 5 sites in United States. Open to participants aged 6 Months to 24 Years. Per ClinicalTrials.gov, last updated 2017-10-26.
Sponsored by University of Michigan · Not applicable, Interventional, and Treatment
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.
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
38 studies on the registry are indexed under Egg Hypersensitivity; 9 are open to participants now.
This study's enrollment of 31 is below the median of 73 across 27 interventional studies indexed under Egg Hypersensitivity.
Browse Egg Hypersensitivity studies →University of Michigan is the lead sponsor of 1,506 studies on the registry; 192 are open to participants now.
Of its 169 completed or terminated interventional studies of FDA-regulated products, 133 (79%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
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).
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.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
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
Age appropriate dose of seasonal Trivalent Influenza Vaccine (TIV), either 0.25mL under age 3 or 0.5mL over the age of 3.
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.
Time frame: 48 hours
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.
Time frame: 6 months
This study was conducted from October 2010 through March 2012 at the University of Michigan.
| Milestone | Single Dose | Graded Challenge |
|---|---|---|
| Started | 17 | 14 |
| Completed | 17 | 14 |
| Not completed | 0 | 0 |
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.
| Participants | Single Dose | Graded Challenge |
|---|---|---|
| No systemic reactivity | 17 | 14 |
| Mild, transient, induration at injection site | 3 | 4 |
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.
No measurements were reported for this outcome.
Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Single Dose | — | 0/17 (0%) | 1/17 (5.9%) |
| Graded Challenge | — | 0/14 (0%) | 2/14 (14.3%) |
| Event | Single Dose | Graded Challenge |
|---|---|---|
| VomitingGastrointestinal disorders | 0/17 | 1/14 |
| TachycardiaCardiac disorders | 0/17 | 1/14 |
| AnaphylaxisSkin and subcutaneous tissue disorders | 1/17 | 0/14 |
| Age, Categorical(Participants) | Single Dose | Graded Challenge | Total |
|---|---|---|---|
| <=18 years | 17 | 14 | 31 |
| Between 18 and 65 years | 0 | 0 | 0 |
| >=65 years | 0 | 0 | 0 |
| Age, Continuous(years) | Single Dose | Graded Challenge | Total |
|---|---|---|---|
| Mean | 5.6 ± 3.4 | 6.3 ± 5.1 | 6.2 ± 4.3 |
| Sex: Female, Male(Participants) | Single Dose | Graded Challenge | Total |
|---|---|---|---|
| Female | 7 | 8 | 15 |
| Male | 10 | 6 | 16 |
| Region of Enrollment(Participants) | Single Dose | Graded Challenge | Total |
|---|---|---|---|
| United States | 17 | 14 | 31 |
| Egg skin test wheal, median, mm(mm) | Single Dose | Graded Challenge | Total |
|---|---|---|---|
| Median | 9 ± 3.4 | 6 ± 4.2 | 7 ± 3.5 |
| Prior TIV(Participants) | Single Dose | Graded Challenge | Total |
|---|---|---|---|
| Count of participants | 12 | 11 | 23 |
| Prior H1N1 Vaccine(Participants) | Single Dose | Graded Challenge | Total |
|---|---|---|---|
| Count of participants | 10 | 6 | 16 |
| History of Anaphylaxis to Egg(Participants) | Single Dose | Graded Challenge | Total |
|---|---|---|---|
| Count of participants | 8 | 6 | 14 |
21 further baseline measures are reported on the registry.
The record gives a start of Oct 2010, a primary completion of May 2012 and a completion of Aug 2012. It does not say whether these dates are actual or estimated.
Results were first posted in Oct 2017, 5 years 5 months after primary completion.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Sep 2017. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.