PneuMum: Pneumococcal Vaccination of Australian Indigenous Mothers

NCT ID: NCT00714064

Last Updated: 2014-07-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

227 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-06-30

Study Completion Date

2011-07-31

Brief Summary

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PneuMum is a randomised controlled trial that aims to find out if pneumococcal vaccination for Australian Indigenous mothers, in the last few months of pregnancy or at delivery, can prevent ear disease in infants. Mothers will receive the 23 valent pneumococcal polysaccharide vaccine (23vPPV) either: a) during the third trimester of pregnancy; b) soon after child birth; or c) seven months after child birth (control group). The adult diphtheria, tetanus and acellular pertussis vaccine (dTpa) will be used as the control vaccine for the birth dose.

The study aims to recruit 210 Indigenous women aged 17-39 years who have an uncomplicated pregnancy. Following recruitment, subjects will be randomly assigned to one of the three groups.

Each mother and infant will be followed from pregnancy until the baby is seven months of age. All routinely recommended vaccinations on the standard vaccination schedule will continue to be offered by the subject's vaccine provider in accordance with current clinical practice.

The primary outcome will be prevalence of middle ear disease at seven months of age, defined as middle ear effusion or tympanic membrane perforation or acute otitis media. Pneumatic otoscopy, video-otoscopy and tympanometry will be used in the ear examinations. The primary analyses will be a direct comparison of the proportion of infants in the control group who have nasopharyngeal carriage of one or more vaccine type pneumococci at seven months of age compared to infants in each of the other two groups. A similar comparison of the proportion with middle ear disease will be undertaken between the control group and the respective intervention group.

Detailed Description

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PneuMum is a randomised controlled trial that aims to find out if pneumococcal vaccination for Australian Indigenous mothers, in the last few months of pregnancy or at delivery, can prevent ear disease in infants. Two vaccines will be used in this trial:

* The 23 valent pneumococcal polysaccharide vaccine (23vPPV), is currently recommended for all Indigenous people in the Northern Territory from 15 years of age but uptake among women of child-bearing age has been low.
* Adult diphtheria, tetanus and acellular pertussis vaccine (dTPa) will be used as the control vaccine. This vaccine is recommended for all new parents who have not previously been immunised but is not currently funded so would normally need to be purchased on prescription through a pharmacist.

Rationale

Indigenous children experience the highest rates of acute and chronic ear infections in the world, resulting in permanent ear damage, hearing loss and educational disadvantage. These infections are mainly bacterial. Streptococcus pneumoniae (pneumococcus) is the predominant pathogen. Pneumococcal colonisation and infection begins within days of birth, months before any potential immunological protection from infant pneumococcal conjugate vaccine may be expected. New strategies are needed to eliminate, or at least delay, this early-onset pneumococcal colonisation.

Maternal vaccination with the 23 valent pneumococcal polysaccharide vaccine (23vPPV) during pregnancy or at delivery is one strategy that may protect newborn infants through mechanisms such as transplacental antibody transfer, increased secretory antibody in breast milk, and/or by reducing nasopharyngeal carriage (and transmission to the infant) of maternal pneumococci. Previous small studies using this strategy have been encouraging, but there have been no studies properly evaluating nasopharyngeal carriage or disease endpoints in infants.

Methods

We aim to recruit 210 Indigenous women aged 17-39 years who have an uncomplicated pregnancy. Following recruitment, subjects will be randomly assigned to one of three groups:

* Group A will receive 23vPPV in the last few months of pregnancy
* Group B will receive 23vPPV soon after childbirth
* Group C will receive 23vPPV seven months after childbirth (the control group).

Women in Groups A and C will receive dTpa soon after childbirth (to conceal the intervention groups), whereas women in Group C will be offered dTpa seven months after childbirth (end of the observation period).

Study participants will be visited at least five times:

1. During the last few months of pregnancy (30-36 weeks gestation)

\- The group of mothers receiving 23vPPV at this visit will also have a pre-vaccination blood sample collected
2. At Royal Darwin Hospital when the baby is born

* Each mother will receive either 23vPPV or dTpa depending on their allocation
* Each mother will have a pre-vaccination blood sample, cord blood sample, a nasopharyngeal swab and a sample of expressed breast milk taken
3. When the baby is one month old

\- Each baby will have their ears checked utilising pneumatic otoscopy, video-otoscopy and tympanometry. A nasopharyngeal swab will be taken. A swab will also be taken of any discharge from the baby's ear/s. Mothers will be asked for sample of expressed breast milk and a post vaccine maternal blood sample will be collected.
4. When the baby is two months old

\- The same checks and samples as the previous month with the exception of maternal blood sample unless this has not previously been collected.
5. When the baby is seven months old - Each mother and baby will have the same checks and samples as per the two month visit. Babies will also have a sample taken of their blood. Mothers who have not yet had 23vPPV will be offered that vaccine as will those who have not yet had dTpa.

Primary Outcome

The primary outcomes will be:1)prevalence of middle ear disease at seven months of age; and 2)prevalence of nasopharyngeal carriage of vaccine type (23vPPV) pneumococci. The primary analyses will be a direct comparison of the proportion of infants in the control group (Group C) who have nasopharyngeal carriage of vaccine type pneumococci at seven months of age compared to infants in each of the other two groups and a similar comparison of the proportion with middle ear disease.

Conditions

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Middle Ear Effusion Tympanic Membrane Perforation Acute Otitis Media Pneumococcal Infections

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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23vPPV in Pregnancy

Group Type ACTIVE_COMPARATOR

23vPPV, dTpa (Pneumovax, Boostrix)

Intervention Type BIOLOGICAL

Group A will receive 23vPPV during 3rd trimester and dTpa at delivery

23vPPV at Birth

Group Type ACTIVE_COMPARATOR

23vPPV, dTpa (Pneumovax, Boostrix)

Intervention Type BIOLOGICAL

Group B will receive 23vPPV at delivery and dTpa 7 months following delivery

Control

Control

Group Type OTHER

23vPPV, dTpa (Pneumovax, Boostrix)

Intervention Type BIOLOGICAL

Group C will receive dTpa at delivery and 23vPPV 7 months following delivery

Interventions

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23vPPV, dTpa (Pneumovax, Boostrix)

Group A will receive 23vPPV during 3rd trimester and dTpa at delivery

Intervention Type BIOLOGICAL

23vPPV, dTpa (Pneumovax, Boostrix)

Group B will receive 23vPPV at delivery and dTpa 7 months following delivery

Intervention Type BIOLOGICAL

23vPPV, dTpa (Pneumovax, Boostrix)

Group C will receive dTpa at delivery and 23vPPV 7 months following delivery

Intervention Type BIOLOGICAL

Other Intervention Names

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Pneumovax, Boostrix Pneumovax, Boostrix Pneumovax, Boostrix

Eligibility Criteria

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Inclusion Criteria

* Singleton uncomplicated pregnancy
* Reside in Darwin, the Tiwi Islands, or other remote community where consent has been obtained
* Intends to deliver child at the Royal Darwin Hospital or other designated hospital where consent has been obtained
* Has given informed consent to participate

Exclusion Criteria

* Had 23vPPV within the previous three years
* Had a previous dose of dTpa
* Intends to leave the study area during the follow-up period
* HIV positive
* History of severe allergy, uncontrolled asthma or splenectomy
Minimum Eligible Age

17 Years

Maximum Eligible Age

39 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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National Health and Medical Research Council, Australia

OTHER

Sponsor Role collaborator

Menzies School of Health Research

OTHER

Sponsor Role lead

Responsible Party

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Ross Andrews

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Ross M Andrews, PhD

Role: PRINCIPAL_INVESTIGATOR

Menzies School of Health Research

Jonathan R Carapetis, PhD

Role: PRINCIPAL_INVESTIGATOR

Menzies School of Health Research

Amanda J Leach, PhD

Role: PRINCIPAL_INVESTIGATOR

Menzies School of Health Research

Peter S Morris, PhD

Role: PRINCIPAL_INVESTIGATOR

Menzies School of Health Research

Edward K Mulholland, DM

Role: PRINCIPAL_INVESTIGATOR

The Univeristy of Melbourne and Murdoch Childrens Research Institute

Paul J Torzillo, MBBS

Role: PRINCIPAL_INVESTIGATOR

Royal Prince Alfred Hospital, Sydney

Mimi LK Tang, PhD

Role: PRINCIPAL_INVESTIGATOR

Royal Children's Hospital

Locations

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Menzies School of Health Research

Darwin, Northern Territory, Australia

Site Status

Countries

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Australia

References

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Martinovich KM, Seppanen EJ, Bleakley AS, Clark SL, Andrews RM, Richmond PC, Binks MJ, Thornton RB, Kirkham LS. Evidence of maternal transfer of antigen-specific antibodies in serum and breast milk to infants at high-risk of S. pneumoniae and H. influenzae disease. Front Immunol. 2022 Sep 21;13:1005344. doi: 10.3389/fimmu.2022.1005344. eCollection 2022.

Reference Type DERIVED
PMID: 36211411 (View on PubMed)

Binks MJ, Moberley SA, Balloch A, Leach AJ, Nelson S, Hare KM, Wilson C, Nelson J, Morris PS, Ware RS, Tang MLK, Torzillo PJ, Carapetis JR, Mulholland K, Andrews RM. Impact of the 23-valent pneumococcal polysaccharide vaccination in pregnancy against infant acute lower respiratory infections in the Northern Territory of Australia. Pneumonia (Nathan). 2018 Dec 25;10:13. doi: 10.1186/s41479-018-0057-2. eCollection 2018.

Reference Type DERIVED
PMID: 30603376 (View on PubMed)

Binks MJ, Moberley SA, Balloch A, Leach AJ, Nelson S, Hare KM, Wilson C, Morris PS, Nelson J, Chatfield MD, Tang ML, Torzillo P, Carapetis JR, Mulholland EK, Andrews RM. PneuMum: Impact from a randomised controlled trial of maternal 23-valent pneumococcal polysaccharide vaccination on middle ear disease amongst Indigenous infants, Northern Territory, Australia. Vaccine. 2015 Nov 27;33(48):6579-87. doi: 10.1016/j.vaccine.2015.10.101. Epub 2015 Oct 31.

Reference Type DERIVED
PMID: 26529076 (View on PubMed)

Related Links

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http://www.clinicaltrials.gov/ct2/show/NCT00310349?term=Pneumum+AND+Australia&rank=1

Previous Registration History - through University of Melbourne

Other Identifiers

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NHMRC 350499

Identifier Type: -

Identifier Source: secondary_id

NHMRC 490320

Identifier Type: -

Identifier Source: org_study_id

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