Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02490007




Registration number
NCT02490007
Ethics application status
Date submitted
30/06/2015
Date registered
3/07/2015
Date last updated
10/08/2020

Titles & IDs
Public title
Pertussis Immunisation and Food Allergy
Scientific title
Case-control Study of the Association Between Pertussis Vaccination in Infancy and the Risk of IgE-mediated Food Allergy
Secondary ID [1] 0 0
CVID/2015-02
Universal Trial Number (UTN)
Trial acronym
PIFA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Food Allergy 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Inflammatory and Immune System 0 0 0 0
Allergies

Intervention/exposure
Study type
Observational
Patient registry
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Allergy Cases - All participants appear on the Australian Childhood Immunisation Register (ACIR) and have received their first pertussis vaccination before the age of 16 weeks. They will have been born during the period of change over from whole cell pertussis vaccine to acellular pertussis vaccine (1997-1999). Allergy case participants have all attended allergy clinics associated with tertiary teaching hospitals. They have confirmed IgE-mediated food allergy as defined by the case description and as ascertained by their medical records.

Controls - All participants appear on the Australian Childhood Immunisation Register (ACIR) and have received their first pertussis vaccination before the age of 16 weeks. They will have been born during the period of change over from whole cell pertussis vaccine to acellular pertussis vaccine (1997-1999).
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Diagnosis of IgE-mediated food allergy
Timepoint [1] 0 0
birth-15 years
Secondary outcome [1] 0 0
Diagnosis of IgE-mediated food allergy
Timepoint [1] 0 0
birth-15 years
Secondary outcome [2] 0 0
Diagnosis of IgE-mediated food allergy
Timepoint [2] 0 0
birth-15 years

Eligibility
Key inclusion criteria
Eligibility Criteria

1. All cases and controls must be registered on ACIR as having had a first dose of any
pertussis containing vaccine before age 16 weeks and during the period of time in which the
transition between aP and wP vaccine occurred; birth dates within 1st Janurary 1997 and
31st December 1999 depending on the jurisdiction.

Case Inclusion Criteria- Cases will be considered to have IgE-mediated food allergy on the
basis of

1. a documented history of consistent clinical symptoms following ingestion of an
implicated food, and

2. evidence of sensitisation to that food via either positive skin-prick test or elevated
specific IgE to the implicated food, with onset after the first pertussis-containing
vaccine but before age 15 years.

IgE-mediated food allergy is defined as BOTH:

1. The clinical notes or clinical letter arising from the allergy consult must explicitly
document the presence of one or more of the following features. Onset of at least one
these features must be within 1 hour of ingestion of suspected food where this can
reasonably inferred from statements such as "immediate", "within x mins" where x is
<60:

- urticaria

- angioedema

- emesis

- vocal hoarseness

- persistent cough

- wheeze

- stridor

- collapse

- hypotension

AND

2. Documented evidence of allergic sensitisation to the implicated food through EITHER:

- specific IgE positive (serum specific IgE >0.35KU/l) to suspected food ), OR

- positive skin prick test (wheal diameter >3mm) against suspected food (SPT)
Evidence of sensitisation must be at the time of consultation or the 6 months
after the clinical encounter for the case to meet definition.
Minimum age
14 Years
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion Criteria- none

Study design
Purpose
Duration
Selection
Timing
Retrospective
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/10/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/12/2018
Sample size
Target
Accrual to date
Final
508
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Princess Margaret Childrens Hospital - Subiaco
Recruitment postcode(s) [1] 0 0
6009 - Subiaco

Funding & Sponsors
Primary sponsor type
Other
Name
Telethon Kids Institute
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Princess Margaret Hospital for Children
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Royal Children's Hospital
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Women's and Children's Hospital, Australia
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Sydney Children's Hospitals Network
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
National Health and Medical Research Council, Australia
Address [5] 0 0
Country [5] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Aim To assess the possible food allergy-preventive benefit of using whole cell pertussis(wP)
vaccination compared with acelluar pertussis vaccine(aP) for whooping cough vaccination in
childhood.

Background Whooping cough, caused by the bacteria, Bordetella pertussis, represents a
significant public health burden in Australia and around the world. Acellular pertussis
vaccination (aP) replaced whole cell vaccination against pertussis (wP) in the late 1990s.
This replacement coincides temporally in an observed rapid rise in the occurrence of severe
food allergy responses. Previous research has suggested that acellular pertussis vaccination
results in the development of immunity that may predispose children to allergic responses. A
retrospective case-controlled trial design, targeting cases of previously diagnosed allergy,
and comparing case vaccination history to that of the whole population, is a powerful means
of assessing the association between immunisation and allergy.

Participant Groups 1000 allergy cases, 10,000 controls

Project Design This is a retrospective individually-matched case-control study of Australian
children born during the period of transition from use of wP vaccines to aP vaccines (year of
birth 1997-1999 inclusive) and who are registered on the Australian Children Immunisation
Register. Cases will be drawn from allergy clinics associated with tertiary teaching
hospitals around Australia.

Methods Cases: will be retrospectively identified from patient lists from allergy clinics
around Australia, born during the period of pertussis vaccine changeover, and be confirmed to
have IgE-mediated food allergy on the basis of 1) a documented history of consistent clinical
symptoms following ingestion of an implicated food, and 2) evidence of sensitisation to that
food via laboratory testing.

Controls: Controls will be sampled from a de-identified database of children born during the
transition from wP to aP vaccination appearing on the ACIR. Cases and controls will be
matched by date of birth (+/-7 days), jurisdiction and socioeconomic decile.

Expected outcomes: Following the study, investigators will be able determine if there is an
association between the type of vaccination received and development of IgE mediated food
allergy. If whole cell vaccination is found to have a protective association against the
development of allergy, this will have profound impact on health policy in Australia and
around the world.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02490007
Trial related presentations / publications
Mullins RJ. Paediatric food allergy trends in a community-based specialist allergy practice, 1995-2006. Med J Aust. 2007 Jun 18;186(12):618-21. doi: 10.5694/j.1326-5377.2007.tb01077.x.
Torvaldsen S, Hull BP, McIntyre PB. Using the Australian Childhood Immunisation Register to track the transition from whole-cell to acellular pertussis vaccines. Commun Dis Intell Q Rep. 2002;26(4):581-3.
Mills KH, Ryan M, Mcguirk P, Griffin F, Murphy G, Mahon B. The immunology of bordetella pertussis infection. Biologicals. 1999 Jun;27(2):77. doi: 10.1006/biol.1999.0183. No abstract available.
Barlow WE, Davis RL, Glasser JW, Rhodes PH, Thompson RS, Mullooly JP, Black SB, Shinefield HR, Ward JI, Marcy SM, DeStefano F, Chen RT, Immanuel V, Pearson JA, Vadheim CM, Rebolledo V, Christakis D, Benson PJ, Lewis N; Centers for Disease Control and Prevention Vaccine Safety Datalink Working Group. The risk of seizures after receipt of whole-cell pertussis or measles, mumps, and rubella vaccine. N Engl J Med. 2001 Aug 30;345(9):656-61. doi: 10.1056/NEJMoa003077.
Feunou PF, Bertout J, Locht C. T- and B-cell-mediated protection induced by novel, live attenuated pertussis vaccine in mice. Cross protection against parapertussis. PLoS One. 2010 Apr 15;5(4):e10178. doi: 10.1371/journal.pone.0010178.
Mills KH, Ryan M, Ryan E, Mahon BP. A murine model in which protection correlates with pertussis vaccine efficacy in children reveals complementary roles for humoral and cell-mediated immunity in protection against Bordetella pertussis. Infect Immun. 1998 Feb;66(2):594-602. doi: 10.1128/IAI.66.2.594-602.1998.
Dannemann A, van Ree R, Kulig M, Bergmann RL, Bauer P, Forster J, Guggenmoos-Holzmann I, Aalberse RC, Wahn U. Specific IgE and IgG4 immune responses to tetanus and diphtheria toxoid in atopic and nonatopic children during the first two years of life. Int Arch Allergy Immunol. 1996 Nov;111(3):262-7. doi: 10.1159/000237376.
Rowe J, Macaubas C, Monger T, Holt BJ, Harvey J, Poolman JT, Loh R, Sly PD, Holt PG. Heterogeneity in diphtheria-tetanus-acellular pertussis vaccine-specific cellular immunity during infancy: relationship to variations in the kinetics of postnatal maturation of systemic th1 function. J Infect Dis. 2001 Jul 1;184(1):80-8. doi: 10.1086/320996. Epub 2001 May 29.
Rowe J, Yerkovich ST, Richmond P, Suriyaarachchi D, Fisher E, Feddema L, Loh R, Sly PD, Holt PG. Th2-associated local reactions to the acellular diphtheria-tetanus-pertussis vaccine in 4- to 6-year-old children. Infect Immun. 2005 Dec;73(12):8130-5. doi: 10.1128/IAI.73.12.8130-8135.2005.
Gruber C, Lau S, Dannemann A, Sommerfeld C, Wahn U, Aalberse RC. Down-regulation of IgE and IgG4 antibodies to tetanus toxoid and diphtheria toxoid by covaccination with cellular Bordetella pertussis vaccine. J Immunol. 2001 Aug 15;167(4):2411-7. doi: 10.4049/jimmunol.167.4.2411.
Public notes

Contacts
Principal investigator
Name 0 0
Thomas Snelling, BMBS PhD
Address 0 0
Telethon Kids Institute
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02490007