PneuMum: Pneumococcal Vaccination of Australian Indigenous Mothers to See if it Protects Their Babies From Ear Disease

Pneumococcal Infections Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT00310349
• Other study ID #: 2 November 2005
• Status: Not yet recruiting
• Phase: Phase 3
• First received: March 31, 2006
• Last updated: December 12, 2007
• Start date: March 2006
• Est. completion date: January 2009

Study information

• Verified date: March 2006
• Source: University of Melbourne
• Contact: Ross M Andrews, PhD
• Phone: 613 9345 4647
• Email: ross.andrews[@]mcri.edu.au
• Is FDA regulated: No
• Health authority: Australia: National Health and Medical Research Council
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 210
• Est. completion date: January 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 16 Years to 39 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Single Blind, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Acute Otitis Media
• Ear Diseases
• Middle Ear Effusion
• Otitis Media
• Otitis Media with Effusion
• Pneumococcal Infections
• Tympanic Membrane Perforation

Intervention

Biological:
• 23 valent pneumococcal polysaccharide vaccine

Locations

Country	Name	City	State
Australia	Menzies School of Health Research	Darwin	Northern Territory

Sponsors (3)

Lead Sponsor	Collaborator
University of Melbourne	Menzies School of Health Research, National Health and Medical Research Council, Australia

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prevalence of ear infection at seven months of age, defined as middle ear effusion or tympanic membrane perforation or acute otitis media
Primary	Nasopharyngeal carriage of vaccine type pneumococci		at seven months of age
Secondary	Prevalence of ear infection		at one month of age
Secondary	Nasopharyngeal carriage of vaccine type pneumococci		at one month of age
Secondary	Prevalence of ear infection		at two months of age
Secondary	Nasopharyngeal carriage of vaccine type pneumococci		at two months of age
Secondary	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		at one, two and seven months of age
Secondary	Impact of each maternal vaccination strategy on breast milk antibody levels to serotypes contained in the vaccine
Secondary	Impact of each maternal vaccination strategy on breast milk antibody avidity (to four selected serotypes)
Secondary	Impact of each maternal vaccination strategy on maternal antibody response to antepartum or postpartum 23vPPV
Secondary	Impact of each maternal vaccination strategy on infant anti-pneumococcal antibody levels		at seven months of age (following the 3rd recommended dose of 7vPCV)