Official Title: “PneuMum: A Randomised Controlled Trial of Pneumococcal Polysaccharide Vaccination for Aboriginal and Torres Strait Islander Mothers to Protect Their Babies From Ear Disease”

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 18-39 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. Children will receive all of their routinely recommended vaccinations in accordance with the standard vaccination schedule.

The primary outcome will be prevalence of ear infection 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 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.

Study Type: Interventional

Study Design: Prevention, Randomized, Single Blind, Placebo Control, Single Group Assignment, Efficacy Study

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 hope to recruit 210 Indigenous women aged 18-39 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 sample taken of their blood

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 sample taken of their blood, the cord blood, a nasopharyngeal swab and a sample of expressed breast milk

3. When the baby is one month old - Each baby will have their ears checked and a nasopharyngeal swab 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.

4. When the baby is two months old - The same checks and samples as the previous month.

5. When the baby is seven months old - Each mother and baby will have the same checks and samples as the previous months.

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 outcome will be prevalence of ear infection 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 (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.

Intervention(s) in this Clinical Trial

• Biological: 23 valent pneumococcal polysaccharide vaccine

Primary Measures

• Prevalence of ear infection at seven months of age, defined as middle ear effusion or tympanic membrane perforation or acute otitis media
• Nasopharyngeal carriage of vaccine type pneumococci
  • Time Frame: at seven months of age
    

Secondary Measures

• Prevalence of ear infection
  • Time Frame: at one month of age
    
• Nasopharyngeal carriage of vaccine type pneumococci
  • Time Frame: at one month of age
    
• Prevalence of ear infection
  • Time Frame: at two months of age
    
• Nasopharyngeal carriage of vaccine type pneumococci
  • Time Frame: at two months of age
    
• Relationship of maternal pneumococcal carriage, maternal anti-pneumococcal antibody levels, cord blood antibody levels and breast milk antibody levels to infant carriage and middle ear disease
  • Time Frame: at one, two and seven months of age
    
• Impact of each maternal vaccination strategy on breast milk antibody levels to serotypes contained in the vaccine
• Impact of each maternal vaccination strategy on breast milk antibody avidity (to four selected serotypes)
• Impact of each maternal vaccination strategy on maternal antibody response to antepartum or postpartum 23vPPV
• Impact of each maternal vaccination strategy on infant anti-pneumococcal antibody levels
  • Time Frame: at seven months of age (following the 3rd recommended dose of 7vPCV)
    

Inclusion Criteria:

• Singleton uncomplicated pregnancy
• Reside in Darwin, Maningrida, Wadeye or the Tiwi Islands
• Intends to deliver child at the Royal Darwin Hospital
• 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

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 16 Years

Maximum Age for this Clinical Trial: 39 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: University of Melbourne

Overall Clinical Trial Officials and Contacts

Ross M Andrews, PhD Principal Investigator The University of Melbourne and Murdoch Childrens Research Institute  

Overall Contact: Ross M Andrews, PhD 613 9345 4647 ross.andrews@mcri.edu.au

Information obtained from ClinicalTrials.gov on February 04, 2010

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00310349

Study ID Number: 2 November 2005

ClinicalTrials.gov Identifier: NCT00310349

Health Authority: Australia: National Health and Medical Research Council