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Trial registered on ANZCTR


Trial ID
ACTRN12613001045707
Ethics application status
Not yet submitted
Date submitted
16/09/2013
Date registered
19/09/2013
Date last updated
19/09/2013
Type of registration
Prospectively registered

Titles & IDs
Public title
Pertussis in Pregnancy Safety (PIPS) Study - Evaluating health outcomes in infants of mothers vaccinated with the tetanus, diphtheria, and pertussis (Tdap) vaccine during pregnancy and to describe the adverse events in pregnant women who received the Tdap vaccine
Scientific title
Pertussis in Pregnancy Safety Study to evaluate health outcomes in infants of mothers vaccinated with tetanus, diphtheria, and pertussis (Tdap)vaccine during pregnancy and to describe adverse events in pregnant women who received Tdap vaccine.
Secondary ID [1] 283220 0
Nil
Universal Trial Number (UTN)
U1111-1148-0718
Trial acronym
Pertussis in Pregnancy Safety (PIPS) Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
health outcomes in infants of mothers vaccinated with Tdap during pregnancy 290092 0
adverse events in pregnant women who received Tdap vaccine 290093 0
Condition category
Condition code
Public Health 290468 290468 0 0
Epidemiology

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
This is a two-component observational study that will collect data both retrospectively and prospectively. Data for all pregnant women and their infants in NZ between 2009 and 2013 will be obtained and pertussis vaccine exposure during pregnancy verified (Study One). A sub-study will actively follow mothers who received Tdap during pregnancy with one also following their infants for upto one year after birth (Study Two ).
Intervention code [1] 287949 0
Not applicable
Comparator / control treatment
All pregnant women who between 2009 and 2013 who did not receive pertussis vaccine exposure
Control group
Active

Outcomes
Primary outcome [1] 290532 0
Primary Outcome 1 : To establish background rated for key endpoints in pregnant women and their infants (Study One).
Timepoint [1] 290532 0
Primary Outcome 1 Timepoint: Data on all women in NZ who were pregnant between 2009 and 2013 will be retrieved from four datasets: National Minimum Dataset for Hospitalisation Data, The National Immunisation Register for Infant Immunisation Data, Notification Data from the ESR, Pregnancy Immunisation records from the HealthPAC claims database. Data will be analysed once collected.
Primary outcome [2] 290533 0
Primary Outcome 2 : To evaluate health outcomes in infants of mothers vaccinated with Tdap during pregnancy (Study Two). The pregnancy safety data will be descriptive in nature, including percentages and 95% confidence intervals. The rates of AEs and SAEs following pertussis vaccine will be discussed in context with the rates previously described pertussis. The expected background rates of MAEs and SAEs for Tdap given during pregnancy are unknown, but as a guide the rates of MAEs for pregnant women receiving influenza vaccine previously reported ranged from 1.1 to 3.8% while the rate of SAEs ranged from 0.4 to 1.5%. Women who have complicated pregnancies will be excluded from the final analyses and described separately. The temporal relationship between onset of events and vaccination will be presented including distribution where appropriate). This is an observational study and in this small study sample we anticipant events to be primary restricted to local injection site reactions such as redness, swelling or induration. There may be reports of systemic events such as malise, fever or headache. This is not an intervention so there is no change in usual practice.
Timepoint [2] 290533 0
Primary Outcome 2 Timepoint: Mothers will be contact by phone as soon as possible after identification to capture any solicited events within the first 48 hours and the first 7 days of receiving vaccine(s). Four weeks post-vaccine administration to pregnant woman (prospective).
Secondary outcome [1] 304631 0
Any difference in hospital-related outcomes of those women vaccinated or not with Tdap during pregnancy will be examined (Study One).
Any difference in birth outcomes and hospital-related outcomes of infants born to mothers vaccinated or not with Tdap during pregnancy will be examined (Study One).
Timepoint [1] 304631 0
Study one- This study is over a five-year period with approximately 325,000 births. The maternal vaccinated is anticipated to increase over the time as the funded vaccine is promoted approximately 30% of mothers are expected to have received vaccination during pregnancy between 2009 and 2013. This data forms part of a population datalink study drawing together four datasets being National Minimum Dataset for hospitalisation data, The National Immunisation Register for infant immunisation data, Notification data from the, ESR, Pregnancy Immunisation records from the HealthPAC claims database. Data will be analysis once collected.


Secondary outcome [2] 304754 0
To describe adverse events in pregnant women who received Tdap vaccine (Study Two). The pregnancy safety data will be descriptive in nature, including percentages and 95% confidence intervals. The rates of AEs and SAEs following pertussis vaccine will be discussed in context with the rates previously described pertussis. The expected background rates of MAEs and SAEs for Tdap given during pregnancy are unknown, but as a guide the rates of MAEs for pregnant women receiving influenza vaccine previously reported ranged from 1.1 to 3.8% while the rate of SAEs ranged from 0.4 to 1.5%.

Women who have complicated pregnancies will be excluded from the final analyses and described separately.

The temporal relationship between onset of events and vaccination will be presented including distribution where appropriate.).
Timepoint [2] 304754 0
Study two will envolve the Practice staff identifying potential participants and providing them with an information sheet summary The first contact with mother by phone (standard script) as soon as possible after identification to capture any solicited events within first 48 hours and first 7 days of receiving vaccine(s). Four weeks post-vaccine administration to pregnant woman (prospective). Phone/written questionnaire will be administered to capture any solicited events in mother up to four weeks after receipt of vaccine

Eligibility
Key inclusion criteria
Study one-NZ women who are pregnant during the study period 2009-2013.
Study two- Pregnant women who have received the Tdap vaccine during pregnancy between 28 and 38 weeks of gestation. Compliant with routine antenatal care, including at least one ultrasound early in pregnancy. Have associated information on the specific vaccines given, including batch number
Minimum age
No limit
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Study 1 no exclusion
Study 2 If a woman has already had her baby prior to being contacted by the study team she will not be enrolled in the study

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Convenience sample
Timing
Both
Statistical methods / analysis
Study one -Logistic regression will be used to estimate odds ratios for the risk for (specific) adverse events for both mothers and infants in vaccine exposed and unexposed groups. Age, ethnicity and socioeconomic deprivation and season for hospital admission will be included as additional explanatory variables.
As specific diagnoses are not necessarily independent events each person will only be counted once for each hospitalisation, the primary diagnosis and repeat admissions for the same episode will be removed, including transfers from one hospital to another.
For diagnosis where individuals may have multiple admissions for different occurrences and the outcome is a count, Poisson regression will be used with testing and adjustment for overdispersion where required.
The temporal relationship between onset of events and vaccination will be presented including distribution where appropriate,
Serious adverse events will be reported as detailed clinical cases.
To analyse the effect of TdaP on still births we will perform a survival analysis. The time dependent explanatory variable of vaccination status and ‘failure’ of still birth and censored at birth, also including demographics as explanatory variables. The independent explanatory variable will be TdaP vaccination status of the mother (time dependent). Time will commence at the beginning of the inclusion time for an individual— 28(20) weeks gestation. Women will be censored at time of live birth or at the end of the study period, 31 December 2013, whichever occurs first.
Study two- The pregnancy safety data will be descriptive in nature, including percentages and 95% confidence intervals. The rates of AEs and SAEs following pertussis vaccine will be discussed in context with the rates previously described pertussis. The expected background rates of MAEs and SAEs for Tdap given during pregnancy are unknown, but as a guide the rates of MAEs for pregnant women receiving influenza vaccine previously reported ranged from 1.1 to 3.8% while the rate of SAEs ranged from 0.4 to 1.5%.
Women who have complicated pregnancies will be excluded from the final analyses and described separately.
The temporal relationship between onset of events and vaccination will be presented including distribution where appropriate.
Serious adverse events will be reported as detailed clinical cases. Other events will be groups according to Brighton Collaboration Definitions.


Recruitment
Recruitment status
Not yet recruiting
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 outside Australia
Country [1] 5413 0
New Zealand
State/province [1] 5413 0

Funding & Sponsors
Funding source category [1] 287971 0
Commercial sector/Industry
Name [1] 287971 0
GlaxoSmithKline Biologicals SA.
Address [1] 287971 0
89 rue de l’Institut, B-1330 Rixensart, Belgium
Country [1] 287971 0
Belgium
Primary sponsor type
University
Name
Uniservices
Address
The University of Auckland,
Private Bag 92019
Victoria St West
Auckland
1142
Country
New Zealand
Secondary sponsor category [1] 286690 0
None
Name [1] 286690 0
Address [1] 286690 0
Country [1] 286690 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 289895 0
Health and Disability Ethics Committees
Ethics committee address [1] 289895 0
Ministry of Health
No 1 The Terrace
PO Box 5013
Wellington
Ethics committee country [1] 289895 0
New Zealand
Date submitted for ethics approval [1] 289895 0
20/09/2013
Approval date [1] 289895 0
Ethics approval number [1] 289895 0

Summary
Brief summary
The rates and patterns of adverse events following administration of Tdap during pregnancy (including the rates and patterns of any adverse pregnancy outcome, and the outcomes in infants up to one year of age), are similar to those where no vaccination during pregnancy occurred
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 42970 0
Dr Helen Petousis-Harris
Address 42970 0
Immunisation Advisory Centre (IMAC)
The University of Auckland
P O Box 17360
Greenlane
Auckland 1546
Country 42970 0
New Zealand
Phone 42970 0
+64 9 923 2078
Fax 42970 0
+64 9 373 7030
Email 42970 0
h.petousis-harris@auckland.ac.nz
Contact person for public queries
Name 42971 0
Mrs Tracey Poole
Address 42971 0
Immunisation Advisory Centre (IMAC)
The University of Auckland
P O Box 17360
Greenlane
Auckland 1546
Country 42971 0
New Zealand
Phone 42971 0
+64 9 923 3806
Fax 42971 0
+64 9 3737030
Email 42971 0
t.poole@auckland.ac.nz
Contact person for scientific queries
Name 42972 0
Dr Helen Petousis-Harris
Address 42972 0
Immunisation Advisory Centre (IMAC)
The University of Auckland
P O Box 17360
Greenlane
Auckland 1546

Country 42972 0
New Zealand
Phone 42972 0
+64 9 923 2078
Fax 42972 0
+64 9 3737030
Email 42972 0
h.petousis-harris@auckland.ac.nz