Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00714064
Other study ID # NHMRC 490320
Secondary ID NHMRC 350499
Status Completed
Phase Phase 3
First received July 10, 2008
Last updated July 9, 2014
Start date June 2006
Est. completion date July 2011

Study information

Verified date July 2014
Source Menzies School of Health Research
Contact n/a
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 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.


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 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.


Recruitment information / eligibility

Status Completed
Enrollment 227
Est. completion date July 2011
Est. primary completion date February 2011
Accepts healthy volunteers Accepts Healthy Volunteers
Gender Female
Age group 17 Years to 39 Years
Eligibility 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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Prevention


Intervention

Biological:
23vPPV, dTpa (Pneumovax, Boostrix)
Group A will receive 23vPPV during 3rd trimester and dTpa at delivery
23vPPV, dTpa (Pneumovax, Boostrix)
Group B will receive 23vPPV at delivery and dTpa 7 months following delivery
23vPPV, dTpa (Pneumovax, Boostrix)
Group C will receive dTpa at delivery and 23vPPV 7 months following delivery

Locations

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

Sponsors (2)

Lead Sponsor Collaborator
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 middle ear disease, defined as middle ear effusion or tympanic membrane perforation or acute otitis media at seven months of age Yes
Primary Nasopharyngeal carriage of vaccine type pneumococci at seven months of age Yes
Secondary Prevalence of middle ear disease at one month of age Yes
Secondary Nasopharyngeal carriage of vaccine type pneumococci at one month of age Yes
Secondary Prevalence of middle ear disease at two months of age Yes
Secondary Nasopharyngeal carriage of vaccine type pneumococci at two months of age Yes
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 Yes
Secondary Impact of each maternal vaccination strategy on breast milk antibody levels to serotypes contained in the vaccine at seven months Yes
Secondary Impact of each maternal vaccination strategy on breast milk antibody avidity (to four selected serotypes) at seven months Yes
Secondary Impact of each maternal vaccination strategy on maternal antibody response to antepartum or postpartum 23vPPV at seven months Yes
Secondary Impact of each maternal vaccination strategy on infant anti-pneumococcal antibody levels (following the 3rd recommended dose of 7vPCV) at seven months of age Yes
See also
  Status Clinical Trial Phase
Completed NCT02201030 - Immunogenicity and Safety Study of NBP606 in Healthy Infants Phase 3
Completed NCT02787863 - Clinical and Immunological Efficiency of Bacterial Vaccines at Adult Patients With Bronchopulmonary Pathology Phase 4
Completed NCT04031846 - Safety, Tolerability, and Immunogenicity of V114 in Healthy Infants (V114-025) Phase 3
Recruiting NCT05920499 - The Effect of AUDIT and Feedback on Pneumococcal Vaccination Coverage N/A
Completed NCT01215175 - Safety and Tolerability Study for the Pneumococcal Conjugate Vaccine V114 Versus Prevnar™ (V114-001) Phase 1
Completed NCT02892812 - A Phase I Clinical Trial of a 13-valent Pneumococcal Conjugate Vaccine and 14-valent Pneumococcal Conjugate Vaccine in Adults Phase 1
Completed NCT02116998 - Safety, Tolerability, and Efficacy Study of Prophylactic S. Pneumoniae Vaccine Following Challenge With S. Pneumoniae Phase 2
Completed NCT01446926 - Study of Investigational Pneumococcal Vaccine in Healthy Adults, Toddlers and Infants Phase 1
Completed NCT01193582 - A Study To Assess The Safety And Effectiveness Of Prevenar In Chinese Children Who Have Not Previously Received A Vaccine Against Pneumococcal Bacteria Phase 4
Completed NCT00744263 - Study Evaluating the Effiacy of a 13-Valent Pneumococcal Conjugate Vaccine (13vPnC) in Adults Phase 4
Completed NCT00492557 - Study Evaluating Safety and Immunogenicity of 13-Valent Pneumococcal Conjugate Vaccine With Influenza Vaccine in Adults Phase 3
Completed NCT00195611 - Study of Streptococcus Pneumoniae in Nose and Throats of Infants With Acute Otitis Media Phase 4
Completed NCT00137605 - Early Versus Delayed Pneumococcal Vaccination in HIV Phase 1/Phase 2
Completed NCT00205803 - Study Evaluating Pneumococcal Vaccine in Healthy Infants Phase 1/Phase 2
Completed NCT02531373 - A Study to Evaluate the Safety, Tolerability and Immunogenicity of V114 in Healthy Adults and Infants (V114-005) Phase 1/Phase 2
Completed NCT03615482 - A Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 When Administered Concomitantly With Influenza Vaccine in Healthy Adults 50 Years of Age or Older (V114-021/PNEU-FLU) Phase 3
Completed NCT03565900 - A Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 in Allogeneic Hematopoietic Stem Cell Transplant Recipients (V114-022/PNEU-STEM) Phase 3
Completed NCT04989465 - A Clinical Trial of 23-valent Pneumococcal Polysaccharide Vaccine Phase 4
Completed NCT02547649 - Safety, Tolerability, and Immunogenicity of Two Formulations of V114 in Healthy Adults 50 Years of Age or Older (V114-006) Phase 2
Completed NCT02573181 - Safety, Tolerability, and Immunogenicity of V114 Compared to Prevnar 13™ in PPSV23-vaccinated Healthy Adults ≥65 Years of Age (V114-007) Phase 2