Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000418673
Ethics application status
Approved
Date submitted
8/03/2023
Date registered
27/04/2023
Date last updated
27/04/2023
Date data sharing statement initially provided
27/04/2023
Date results provided
27/04/2023
Type of registration
Retrospectively registered

Titles & IDs
Public title
Persistence of immunity and response to a booster dose of DTPa or dTpa vaccine at 18 months old following acellular pertussis vaccine given at birth in healthy infants
Scientific title
A follow up study of Neonatal pertussis vaccination in infants. Response to a booster dose of DTPa or dTap at 18 months old and persistence of immunity following neonatal acellular pertussis vaccination
Secondary ID [1] 307993 0
Nil known
Universal Trial Number (UTN)
Nil known
Trial acronym
Linked study record
This study is a follow up of the infants enrolled on study with registration record ACTRN12609000905268

Health condition
Health condition(s) or problem(s) studied:
Vaccine 327656 0
Pertussis 327657 0
Immunity persistence 327658 0
Condition category
Condition code
Inflammatory and Immune System 324743 324743 0 0
Other inflammatory or immune system disorders
Infection 324744 324744 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All participants in this study will have participated in the neonatal pertussis vaccine trial (ACTRN12609000905268).
Participants on this initial study (ACTRN12609000905268) were randomised to two intervention groups at birth. One group received acellular pertussis vaccine and hepatitis B vaccine before 5 days old and the other group received only hepatitis B vaccine at birth.

In this follow on study participants from the original trial, both those who received acellular pertussis and hepatitis B vaccine at birth and those who received only hepatitis B vaccine at birth, were invited to receive either DTPa vaccine or a low dose dTpa vaccine at 18 months old.

One intervention subgroup received a booster dose of Infanrix (Registered trademark) (DTPa) at 18 months of age.
Each 0.5 mL monodose vial or pre-filled syringe of Infanrix contains:
greater than or equal to 30 IU diphtheria toxoid
greater than or equal to 40 IU tetanus toxoid
equals 25 µg pertussis toxoid
equals 25 µg filamentous haemagglutinin
equals 8 µg pertactin
Adsorbed onto 0.5 mg aluminium as aluminium hydroxide.

The other intervention subgroup received a booster dose of Boostrix (Registered trademark) (dTpa) at 18 months old. Boostrix contains a lower amount of each of diphtheria, tetanus and pertussis antigens.
Each 0.5 mL monodose vial or pre-filled syringe of Boostrix contains:
greater than or equal to 2 IU diphtheria toxoid
greater than or equal to 20 IU tetanus toxoid
equals 8 µg pertussis toxoid
equals 8 µg filamentous haemagglutinin
equals 2.5 µg pertactin
Adsorbed onto 0.5 mg aluminium as aluminium hydroxide and aluminium phosphate

In this follow on study the aim was to compare surrogate measures of protection (IgG antibody) against pertussis prior to and following a DTPa or low dose dTap booster vaccine at 18 months old in children previously recruited in the primary birth pertussis vaccine study

No additional booster vaccines were given in this study. Children enrolled on the study were given the routine immunization program at 12 months of age prior to enrolment in this study
Intervention code [1] 324447 0
Prevention
Comparator / control treatment
Participants form the original study ACTRN12609000905268 were followed up to 18-36 months of age and immunogenicity measured pre and post a DTaP (Infanrix) vaccine
Control group
Active

Outcomes
Primary outcome [1] 332563 0
To compare surrogate measures of protection (IgG antibody) against pertussis antigens prior to and following a DTPa or dTap booster vaccine at 18 months old in children previously recruited to a study of a birth dose pertussis vaccine study.

The IgG antibodies to pertussis antigens will be measured on blood sera samples collected from participants in the trial
Timepoint [1] 332563 0
Serology will be measured at 18 months old - prior to receipt of the DTaP or dTpa booster vaccine and at 1 month after of DTPa or dTpa vaccine
Secondary outcome [1] 413933 0
In children previously recruited to the birth dose pertussis vaccine schedule evaluate adverse reactions following the 18 month old DTPa or dTpa booster vaccination.
Adverse events will be measured by the use of diary cards (routinely used in vaccine trials) that collect solicited information on local and systemic adverse events.
Local adverse events include pain, redness and swelling at the injection site. Systemic adverse events includes, headache, fever and myalgia. Serious adverse events will also be collected during the study.
Timepoint [1] 413933 0
Local and systemic adverse events will be assessed daily for 7 days and serious adverse events assessed for 30 days post receipt of DTPa or dTpa booster vaccine (at age 18 months).
Secondary outcome [2] 413935 0
In children previously recruited to the birth dose pertussis vaccine study:
Evaluate diphtheria antibodies following the 18 month old DTPa or dTpa booster vaccination.

IgG antibodies to diphtheria will be measured on serology/blood samples collected prior to receipt of the 18 month old DTaP or dTp vaccine and 1 month after receipt of DTPa or dTpa vaccine.
Timepoint [2] 413935 0
18 months - prior to receipt of the DTPa or dTpa vaccine and 1 month after receipt of DTPa od dTpa vaccine
Secondary outcome [3] 420418 0
In children previously recruited to the birth dose pertussis vaccine study:
Evaluate tetanus antibodies following the 18 month old DTPa or dTpa booster vaccination.

IgG antibodies to tetanus will be measured on serology/blood samples collected prior to receipt of the 18 month old DTaP or dTp vaccine and 1 month after receipt of DTPa or dTpa vaccine.
Timepoint [3] 420418 0
30 days post receipt of DTPa or dTpa booster vaccine

Eligibility
Key inclusion criteria
Children who are between 18 to 36 months old and were subjects previously enrolled in the
First Phase study (ACTRN12609000905268) are eligible to participate in this study.
Eligible children must meet inclusion and exclusion criteria at the time of first planned visit and parents/guardians must give written informed consent.
Minimum age
18 Months
Maximum age
36 Months
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Contraindications to vaccination as listed in the NHMRC Australian
Immunisation Handbook or as listed in the Infanrix Product
Information. DTPa or 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).

Administration of immunoglobulins and any blood products within the 3 month
period prior to the first visit or planned administration during the study period; in
which case, a delay in enrolment will be considered in the absence of other excluding
criteria.

Any confirmed or suspected immunosuppressive or immunodeficient condition.

History of serious chronic illness or condition which in the judgement of the clinical
investigator would preclude study participation.

History of neurologic disease or seizure

Must not have had a DTPa or dTpa booster vaccine in the second year of life (prior to study
enrolment)

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by computer at the NHMRC Clinical trial centre
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using an interactive voice response system created by computer software at the NHMRC clinical trial centre.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Other
Other design features
Follow up of participants who participated in the 2+1 primary vaccine study ACTRN12609000905268 will be randomised to receive DTPa or dTpa at 18-36 months of age.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Immunogenicity: Continuous (geometric mean antibody concentration) and categorical
(presumptive threshold) measures of antibodies to pertussis and other contemporaneously
administered antigens will be examined. All serum antibody concentrations will be log
transformed for statistical analysis as geometric mean concentrations (GMC) with 95%
confidence limits.

Where protective thresholds are well-established, the proportions with
95% confidence limits at or above the assay cut off will be calculated – anti-diphtheria (0.1
IU/ml)*, anti-tetanus (0.1 IU/ml). Antibody to polio serotypes 1, 2 and 3 will be measured by
microneutralisation assay and the lowest dilution tested at 1:8.

Statistical analysis will include both comparisons of GMC (with 95% confidence intervals) as a continuous variable. (Student’s t-test) and categorical analysis of relevant antibody thresholds (Chi square). The frequency of seroresponses defined as a 4-fold increase from pre-vaccination antibody level will be compared between our study group and the NHMRC Birth Pertussis Study (historical control) cohort by the Chi square test statistic.

Note: * this threshold is significantly above the known protective level of 0.01 IU/ml but is
the lower limit of assay detection.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
13/05/2016
Date of last participant enrolment
Anticipated
Actual
14/03/2017
Date of last data collection
Anticipated
Actual
22/05/2019
Sample size
Target
60
Accrual to date
Final
47
Recruitment in Australia
Recruitment state(s)
NSW,SA,WA
Recruitment hospital [1] 23168 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [2] 24217 0
Womens and Childrens Hospital - North Adelaide
Recruitment hospital [3] 24218 0
Perth Children's Hospital - Nedlands
Recruitment postcode(s) [1] 38532 0
2145 - Westmead
Recruitment postcode(s) [2] 39750 0
5006 - North Adelaide
Recruitment postcode(s) [3] 39751 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 312256 0
Hospital
Name [1] 312256 0
The Sydney Children's Hospital Network
Country [1] 312256 0
Australia
Funding source category [2] 312257 0
Commercial sector/Industry
Name [2] 312257 0
GlaxoSmithKline
Country [2] 312257 0
Australia
Primary sponsor type
Hospital
Name
The Sydney Children's Hospital Network
Address
The Children's Hospital at Westmead
Locked Bag 4001
Westmead NSW 2145
Country
Australia
Secondary sponsor category [1] 313798 0
None
Name [1] 313798 0
Address [1] 313798 0
Country [1] 313798 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311632 0
The Sydney Children's Hospital Network
Ethics committee address [1] 311632 0
Ethics committee country [1] 311632 0
Australia
Date submitted for ethics approval [1] 311632 0
Approval date [1] 311632 0
16/09/2015
Ethics approval number [1] 311632 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 121786 0
Dr Nicholas Wood
Address 121786 0
Locked Bag 4001
National Centre for Immunisation Research and Surveillance
Cnr Hainsworth St and Hawkesbury Rd
The Children’s Hospital at Westmead
Westmead NSW 2145
Country 121786 0
Australia
Phone 121786 0
+61 2 9845 1433
Fax 121786 0
Email 121786 0
[email protected]
Contact person for public queries
Name 121787 0
Nicholas Wood
Address 121787 0
Locked Bag 4001
National Centre for Immunisation Research and Surveillance
Cnr Hainsworth St and Hawkesbury Rd
The Children’s Hospital at Westmead
Westmead NSW 2145
Country 121787 0
Australia
Phone 121787 0
+61 2 9845 1433
Fax 121787 0
Email 121787 0
[email protected]
Contact person for scientific queries
Name 121788 0
Nicholas Wood
Address 121788 0
Locked Bag 4001
National Centre for Immunisation Research and Surveillance
Cnr Hainsworth St and Hawkesbury Rd
The Children’s Hospital at Westmead
Westmead NSW 21455
Country 121788 0
Australia
Phone 121788 0
+61 2 9845 1433
Fax 121788 0
Email 121788 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No ethics approval to do so.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.