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Trial registered on ANZCTR


Trial ID
ACTRN12614000374662
Ethics application status
Approved
Date submitted
31/03/2014
Date registered
8/04/2014
Date last updated
8/04/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
Optimising Protection for Pregnant Women with Influenza Vaccination
Scientific title
Optimising Protection for Pregnant Women with Influenza Vaccination
Secondary ID [1] 284353 0
Nil
Universal Trial Number (UTN)
Trial acronym
OptiMum
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Influenza vaccination in obese and non-obese pregnant women 291508 0
Condition category
Condition code
Public Health 291878 291878 0 0
Other public health
Diet and Nutrition 291900 291900 0 0
Obesity
Infection 291950 291950 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Approximately 300 pregnant women will be enrolled in this study at the Women’s and Children’s Hospital over two influenza seasons. Whilst recruitment will not be targeting any specific BMI of potential participants, we expect that approximately 150 obese and non-obese participants will be enrolled in 2014 and 2015. This is a prospective cohort study including obese and non-obese pregnant women to assess difference in seroprotective status after a seasonal influenza vaccination given according to standard practice. All pregnant women will be administered 1 (0.5ml) dose of the licensed influenza vaccine into the upper deltoid muscle of the arm.

Group 1: Participants with a BMI >=30kg/m2
Group 2: Participants with a BMI <30kg/m2

All participants will have a follow-up 28 days after vaccination to assess antibody responses.
Intervention code [1] 289079 0
Treatment: Drugs
Comparator / control treatment
Obese and non obese pregnant women will be compared. All participants will received a standard licensed influenza vaccine (as recommended). Immunogenicity following vaccination will be compared to determine the impact of obesity on immune response.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 291798 0
Paired sera will be collected pre- and post-vaccination for the assessment of vaccine immunogenicity, using haemagglutination inhibition (HI) against vaccine-related viruses. Samples will be batched, collected and sent frozen to the WHO Collaborating Centre for Reference and Research on Influenza.

HI titres >=40 are accepted as a correlate of protective efficacy for influenza vaccines. The primary outcome will be the proportion with seroprotective HI titres >=40 and differences betwen obese and non obese groups assessed using chi square tests and logistic regression.
Timepoint [1] 291798 0
end of 2014 and end of 2015
Primary outcome [2] 291799 0
geometric mean anti-influenza virus antibody concentrations will be assessed and reported on paired sera ( pre and post vaccination) via assays conducted by the WHO Collaborating Centre for Reference and Research on Influenza. The proportion achieving a four-fold rise in titres post influenza vaccination between obese and non obese groups will be assessed statistically for differences .
Timepoint [2] 291799 0
end of 2014 and 2015
Primary outcome [3] 291800 0
Geometric mean anti-influenza virus antibody concentrations will be assessed and reported on paired sera ( pre and post vaccination) via assays conducted by the WHO Collaborating Centre for Reference and Research on Influenza. Geometric mean titres and the mean geometric increase will be assessed statistically using appropriate descriptive and inferential statistics (ie. to compare obese vs non obese groups)
Timepoint [3] 291800 0
end of 2014 and 2015
Secondary outcome [1] 307575 0
The proportion of women with altered cytokines (elevated or reduced).
Serum cytokines will be measure using a standardised commercial human cytokine assay kit. Proportions with altered cytokines will be reported for obese and non-obese groups with differences assessed using chi square tests.
Timepoint [1] 307575 0
end of 2014 and 2015
Secondary outcome [2] 307576 0
The average cytokine levels will be reported for :
a) Obese vs non obese women
b) Women achieving haemagglutination inhibition (HI) assay titres >=40 vs women not achieving >=40

Serum cytokines will be measure using a standardised commercial human cytokine assay kit and reported using descriptive statistics
Timepoint [2] 307576 0
end of 2014 and 2015

Eligibility
Key inclusion criteria
*Pregnant women aged 18 to 40 years (inclusive) at the time of the vaccination.
*Written informed consent obtained from the participant.
*Ability to understand the information sheet and provide informed consent
*Participants who in the opinion of the study staff can and will comply with the requirements of the protocol (eg return for follow-up visits, blood collection)
Minimum age
18 Years
Maximum age
40 Years
Gender
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
*Any major illness that, in the investigator’s judgment, will substantially increase the risk associated with the subject’s participation in the study, or interfere with the evaluation of the study objectives.
*History of serious medical conditions (eg cardiac, respiratory, renal, hepatic disorders, diabetes mellitus requiring treatment with insulin).
*History of seasonal influenza vaccination within the last six months prior to enrolment.
*History of any immunosuppressive condition (eg HIV infection) or on immunosuppressing medication.
*Any contraindication to influenza immunisation according to the Australian Immunisation Handbook.
*Anaphylaxis following a previous dose of any influenza vaccine
*Anaphylaxis following any vaccine component.
*History of egg allergy.
*History of Gullain Barre syndrome.
*Bleeding diathesis or condition associated with prolonged bleeding that may contraindicate intramuscular injection or blood draw, including participants taking anticoagulant medications or antiplatelet therapy (except for low dose daily aspirin therapy) within 30 days before enrolment.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Type of endpoint(s)
Statistical methods / analysis

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 in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 2256 0
Womens and Childrens Hospital - North Adelaide
Recruitment postcode(s) [1] 7923 0
5006 - North Adelaide

Funding & Sponsors
Funding source category [1] 288987 0
Charities/Societies/Foundations
Name [1] 288987 0
Women's and Children's Hospital Foundation
Address [1] 288987 0
55 King William Road
North Adelaide
SA 5006
Country [1] 288987 0
Australia
Primary sponsor type
Hospital
Name
Women's and Children's Hospital
Address
72 King William Road
North Adelaide
South Australia 5006
Country
Australia
Secondary sponsor category [1] 287684 0
None
Name [1] 287684 0
Address [1] 287684 0
Country [1] 287684 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290796 0
Women's and Children's Health Network Human Research Ethics Committee
Ethics committee address [1] 290796 0
72 King William Road
North Adelaide
South Australia 5006
Ethics committee country [1] 290796 0
Australia
Date submitted for ethics approval [1] 290796 0
Approval date [1] 290796 0
25/03/2014
Ethics approval number [1] 290796 0
HREC/14/WCHN/3

Summary
Brief summary
Pregnant women are at greater risk of complications from influenza infection and vaccination provides the best protection against influenza to pregnant women and their infants. Since 2010, the Australian Government has provided free seasonal influenza vaccine to all pregnant women (in any trimester).

Whilst there are numerous data suggesting that influenza vaccination during pregnancy is beneficial to the mother and infant, there is limited data on factors that could potentially reduce the effectiveness of the influenza vaccine response in pregnant women. It is possible factors such as body mass index (BMI), may influence the immune response to influenza vaccine. Studies have shown that obese adults are at increased risk of severe disease from influenza and the immune response to some inactivated vaccines is reduced.

The main objective of this study is to determine whether there is any relationship between BMI and the effectiveness of influenza vaccination in pregnant women. Approximately 300 pregnant women will be enrolled in this study at Women’s and Children’s Hospital over two influenza seasons (2014 and 2015). Approximately 150 obese and 150 non-obese participants will be enrolled. Licensed 2014 or 2015 seasonal influenza vaccines will be provided to all participants, with the vaccine administered during ultrasound imaging for a subset of pregnant women (n=70) to determine exact location of vaccine deposition. Two blood samples will be collected from all participants during the study (at baseline and at approximately 28 days post vaccination) in order to assess antibody responses to the vaccine. We will also measure cytokines (IL6 + TNFa) to determine associations with obesity and immunogenicity.

In addition, for influenza vaccines we don’t know whether the immune response is different for people who receive the influenza vaccine subcutaneously vs intramuscularly. We will investigate whether obesity is associated with a lower likelihood of intramuscular vaccination and the implication of this for immune response. As it is likely that many pregnant women do not receive the influenza vaccine (standard fixed 16mm needle) intramuscularly.

This study will inform vaccine policy and guidelines by providing evidence on the impact of BMI on influenza vaccine response for pregnant women.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 47326 0
A/Prof Helen Marshall
Address 47326 0
Discipline of Paediatrics
Women's and Children's Hospital
72 King William Road
North Adelaide
South Australia 5006
Country 47326 0
Australia
Phone 47326 0
+618 81618115
Fax 47326 0
+618 81617031
Email 47326 0
helen.marshall@adelaide.edu.au
Contact person for public queries
Name 47327 0
A/Prof Helen Marshall
Address 47327 0
Discipline of Paediatrics
Women's and Children's Hospital
72 King William Road
North Adelaide
South Australia 5006
Country 47327 0
Australia
Phone 47327 0
+618 81618115
Fax 47327 0
+618 81617031
Email 47327 0
helen.marshall@adelaide.edu.au
Contact person for scientific queries
Name 47328 0
A/Prof Helen Marshall
Address 47328 0
Discipline of Paediatrics
Women's and Children's Hospital
72 King William Road
North Adelaide
South Australia 5006
Country 47328 0
Australia
Phone 47328 0
+618 81618115
Fax 47328 0
+618 81617031
Email 47328 0
helen.marshall@adelaide.edu.au