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Trial registered on ANZCTR


Registration number
ACTRN12615001262594
Ethics application status
Approved
Date submitted
11/11/2015
Date registered
19/11/2015
Date last updated
12/06/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Duration of Pertussis Immunity in Adults: a study of Healthcare Workers.
Scientific title
A non-randomised cohort study to evaluate immunogenicity and reactogenicity of adult formulation diphtheria-tetanus-pertussis vaccine in healthy adult healthcare workers and researchers working with children: a comparison of those who have previously received a booster and those who are previously unvaccinated
Secondary ID [1] 287874 0
Telethon Kids Institute - VTG 2015P03
Universal Trial Number (UTN)
N/A
Trial acronym
N/A
Linked study record

Health condition
Health condition(s) or problem(s) studied:
A study analysing the duration of Immunity to Pertussis booster vaccine in Health Care workers to establish guidelines when boosters are required. 296755 0
Condition category
Condition code
Infection 296987 296987 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
In this study all participants will receive a combined diphtheria-tetanus-acellular pertussis vaccine, Boostrix 'Trademark' (dTpa) single intramuscular injection.

Each dose (0.5 ml) of dTpa contains greater than or equal to 2 IU diphtheria toxoid, greater than or equal to 20 IU tetanus toxoid, 8g pertussis toxin (PT), 8g filamentous haemagglutinin (FHA) and 2.5g pertactin (PRN), adsorbed on 0.5mg aluminium and suspended in isotonic sodium chloride. It also contains formaldehyde, polysorbate 80 and glycine in residual amounts.
Intervention code [1] 293240 0
Prevention
Comparator / control treatment
Every participant in the study will receive a booster vaccine of Boostrix 'Trademark'. These participants will be allocated to 2 groups, Health care workers who have previously received a booster Boostrix 'Trademark' vaccine compared to Health care workers and Researchers who work with children who have not received a booster Boostrix 'Trademark' vaccine to compare duration of immunity immunogenicity and reactogenicity to booster immunisation. No subjects will be given a placebo.
Control group
Active

Outcomes
Primary outcome [1] 296591 0
Pertussis toxin IgG antibody response as measured by multiplex fluorescent bead assay.
Timepoint [1] 296591 0
Pre vaccine, 1 and 12 months post-dTap booster.

Primary outcome [2] 296615 0
Filamentous haemagglutinin IgG antibody response as measured by multiplex fluorescent bead assay.
Timepoint [2] 296615 0
Pre vaccine, 1 and 12 months post-dTap booster.

Primary outcome [3] 296616 0
Pertactin IgG antibody response as measured by multiplex fluorescent bead assay.

Timepoint [3] 296616 0
Pre vaccine, 1 and 12 months post-dTap booster.

Secondary outcome [1] 318822 0
Pertussis-specific T-cell memory response as measured using cytokine and qRT PCR.


Timepoint [1] 318822 0
Pre vaccine, 1 week and 1 month post-dTap booster.
Secondary outcome [2] 318823 0
Pertussis specific B-cell memory response as measured using ELISpot.
Timepoint [2] 318823 0
Pre vaccine, 1 week and 1 month post-dTap booster
Secondary outcome [3] 318931 0
Frequency of injection site redness or swelling > 50mm as measured by analysis of clinical data. Subjects will complete a 7-day diary documenting solicited local reactions and systemic symptoms and provided with ruler and thermometer.

Timepoint [3] 318931 0
1-7 days post vaccination

Eligibility
Key inclusion criteria
Inclusion criteria:
1. Healthy adults 23 - 64 years of age employed in the Child and Adolescent Health
Service, North and South Metro Health Service, University of WA School of Paediatrics
and Child Health and/or Telethon Kids Institute, in general good health, available for
the duration of the study.
2. Participants will have either received a dTPa vaccine 7-10 years previously or have not
received a pertussis containing vaccine since childhood (<15 years of age).

Minimum age
23 Years
Maximum age
64 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion criteria:
1. History of pertussis, tetanus or diphtheria vaccination or confirmed pertussis in the
previous 5 years;
2. Immunosuppressive therapy or known immunodeficiency;
3. Immunoglobulins and blood products within 3 months prior to or during the trial;
4. Acute febrile illness at the time of enrolment; or previous record, following of serious
adverse reaction to diphtheria-tetanus-pertussis vaccination or component antigens.
5. Females will be excluded if they are pregnant/ or nursing.
6. Contraindications to vaccination as listed in the current NHMRC Australian
Immunisation Handbook 10th Edition or as listed in the Boostrix 'Trademark' Product
Information. dTpa vaccine will not be administered to individuals known to be
hypersensitive to any component of the vaccine or residues carried over from
manufacture (such as formaldehyde and glutaraldehyde).
7. History of serious chronic illness or condition which in the judgement of the clinical
investigator would preclude study participation.
8. History of neurologic disease or seizure (excluding simple febrile seizure).


Study design
Purpose of the study
Prevention
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
N/A
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
N/A
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Every participant in the study will receive a booster vaccine of Boostrix 'Trademark'. These participants will be allocated to 2 groups, Health care workers who have previously received a booster Boostrix 'Trademark' vaccine compared to Health care workers and Researchers who work with children who have not received a booster Boostrix 'Trademark' vaccine to compare duration of immunity immunogenicity and reactogenicity to booster immunisation. No subjects will be given a placebo.
Phase
Phase 4
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Sample Size
A sample size of 72 subjects in each group will provide 80% power to achieve the primary objective, assuming a seroprotection rate of at least 86% for pertussis antigens in the previously vaccinated cohort and 70% seroprotection rate in the unvaccinated adults based on previous studies in Australian adults. This sample size will also allow us to detect an increase in injection site reactions from 1% to 15% in adults being revaccinated. Therefore 75 adults will be recruited to each group.
Statistical Analysis
Analysis will be calculated with 95% CI.
The primary analysis of immunogenicity will be performed on the according to protocol cohort.
Serologic analyses: Analaysis will be determined with a 95% CI. The percentage of subjects who have a seroresponse to the vaccine with titres above the assay cut-off for each antigen, prior to vaccination and 1 month after vaccination will be compared using a two-sided Fisher Exact test. Geometric mean antibody concentrations (GMCs) will be calculated from the anti-log of the mean of log-transformed values and will be compared between groups by unpaired Student’s t-tests or Wilcoxon test (if conditions were non-parametric). Antibody concentrations below the assay cut-off will be given an arbitrary value of half the cut-off for the purpose of GMC calculation.
Cell mediated immune response analyses: Univariate analysis will be used determine significant differences between vaccination groups (Mann-Whitney U test for unpaired responses) and for analysis of responses before- and after-vaccination for each individual (Wilcoxon matched-pair signed-rank test). Correlations between continuous variables will be assessed using Spearman rank correlational categorical coefficient. Stepwise logistical regression modelling will be used to further examine associations between local reactions and immunological indices.
Reactogenicity and safety analyses of the total vaccinated cohort: The incidence and intensity of solicited local and general adverse events reported during the 7-day follow-up period, and unsolicited events reported for 30 days after vaccination. SAEs and large injection site swelling reactions will be described.



Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 4608 0
Princess Margaret Hospital - Subiaco
Recruitment postcode(s) [1] 12210 0
6008 - Subiaco

Funding & Sponsors
Funding source category [1] 292370 0
Commercial sector/Industry
Name [1] 292370 0
GlaxoSmithKline
Address [1] 292370 0
GlaxoSmithKline Australia Pty Limited
PO BOX 309
AUBURN NSW 1835
Country [1] 292370 0
Australia
Primary sponsor type
Other
Name
Telethon Kids Institute
Address
100 Roberts Road
Subiaco WA 6008
Country
Australia
Secondary sponsor category [1] 291057 0
None
Name [1] 291057 0
Address [1] 291057 0
Country [1] 291057 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293844 0
Sir Charles Gairdner Group (SCGG) Human Research Ethic Committee
Ethics committee address [1] 293844 0
Level 2 A Block Hospital Ave
NEDLANDS WA 6009
Ethics committee country [1] 293844 0
Australia
Date submitted for ethics approval [1] 293844 0
15/07/2015
Approval date [1] 293844 0
14/09/2015
Ethics approval number [1] 293844 0
HREC 2015-099

Summary
Brief summary
The aim of this study is to assess antibody persistence and cell-mediated immunity post administration of combined diphtheria-tetanus-acellular pertussis vaccine, Boostrix 'Trademark' (dTpa) in healthy adults who have received adult formulation diphtheria-tetanus-pertussis boosters 5-10 previously, compared to those that have not received a pertussis containing vaccine since childhood (<15 years of age).

Health care workers (HCWs) in paediatric hospitals have been recommended to receive pertussis booster immunisations (Australian Immunisation Handbook 2013) as they are both at increased exposure to pertussis in the hospital and can cause nosocomial transmission to their patients. A booster dTpa immunisation (Boostrix™) is approved for use in Australia by the Therapeutic Goods Administration (TGA). It is now almost 10 years since Boostrix™ was introduced into Western Australia (2004) with high uptake by employees at Princess Margaret Hospital for Children in Perth and health care workers are being offered revaccination. Little is known about the duration of pertussis immunity in adults. No studies have yet provided an in-depth analysis of the immune responses induced by acellular pertussis vaccines and how fast these may wane over time.

This study is a non-randomised cohort study. We propose to recruit a total of 150 healthy adults aged 23-64 years employed in the Child and Adolescent Health Service, University of WA School of Paediatrics and/or Telethon Kids Institute.

Participants will be asked to attend 4 clinic visits over a 12 month period. These visits will take place at the Clinical Child Research Facility at Princess Margaret Hospital. Participants will be allocated to one of 2 groups depending upon whether or not they have previously received a booster for pertussis.

During the first visit participants will be asked about their medical history, demographic data and previous reactions to vaccinations. Immunisation histories will be confirmed (if required) through hospital and GP records. In addition a brief medical directed medical examination may be conducted and vital signs will be taken. Females of child bearing potential will need to do a urine pregnancy test prior to vaccination. A blood sample of 25-30mls will be taken by trained staff before participants are vaccinated with Boostrix™. Following this, a 7 day diary documenting local reactions and adverse events will need to be completed.

Further blood tests of 25-30mls will be taken 1 week, 4 weeks and 1 year post-vaccination. Safety data will be collected at each of these visits.
Trial website
N/A
Trial related presentations / publications
N/A
Public notes
N/A

Contacts
Principal investigator
Name 61170 0
Prof Peter Richmond
Address 61170 0
Director
Vaccine Trials Group
Telethon Kids Institute
100 Roberts Road
SUBIACO WA 6008
Country 61170 0
Australia
Phone 61170 0
+61 8 9340 7037
Fax 61170 0
+61 8 9340 8402
Email 61170 0
peter.richmond@uwa.edu.au
Contact person for public queries
Name 61171 0
Ms Jennifer Kent
Address 61171 0
Vaccine Trials Group
Telethon Kids Institute
100 Roberts Road
SUBIACO WA 6008
Country 61171 0
Australia
Phone 61171 0
+61 8 9340 8883
Fax 61171 0
+61 8 9340 8402
Email 61171 0
jennifer.kent@telethonkids.org.au
Contact person for scientific queries
Name 61172 0
Prof Peter Richmond
Address 61172 0
Director
Telethon Kids Institute
100 Roberts Road
SUBIACO WA 6008
Country 61172 0
Australia
Phone 61172 0
+61 8 9340 7037
Fax 61172 0
+61 8 9340 8402
Email 61172 0
peter.richmond@uwa.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary