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Trial registered on ANZCTR


Registration number
ACTRN12618000150246p
Ethics application status
Not yet submitted
Date submitted
26/01/2018
Date registered
1/02/2018
Date last updated
1/02/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
PneuMatters: maternal immunisation to prevent pneumonia in children
Scientific title
A multi-centre, observer blinded, randomised controlled trial to evaluate the efficacy of the 10 valent pneumococcal-Protein D conjugate (PHiD-CV) vaccine administered during pregnancy in preventing acute lower respiratory infection (ALRI) in Australian Indigenous and Malaysian infants up to 12 months of age, compared to infants whose mothers were not vaccinated in pregnancy.
Secondary ID [1] 293886 0
NHMRC APP 1138555
Universal Trial Number (UTN)
U1111-1208-5603
Trial acronym
PneuMatters
Linked study record
N/A

Health condition
Health condition(s) or problem(s) studied:
Acute Lower Respiratory Infection 306355 0
Condition category
Condition code
Respiratory 305443 305443 0 0
Other respiratory disorders / diseases
Infection 305462 305462 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Pneumococcal polysaccharide conjugate vaccine, 10 valent adsorbed, 1 dose of 0.5mls administered intramuscularly to pregnant women between 28 - 34 weeks gestation. The vaccine will be administered by an accredited nurse immuniser.
Intervention code [1] 300156 0
Prevention
Comparator / control treatment
Controls receive no intervention
Control group
Active

Outcomes
Primary outcome [1] 304578 0
Proportion of infants with any medically attended acute lower respiratory tract infection in infants assessed by parent report which is then validated by medical record review.
Timepoint [1] 304578 0
12 months of age
Primary outcome [2] 304579 0
Incidence of medically attended ALRI in infants assessed by parent report which is then validated by medical record review.
Timepoint [2] 304579 0
12 months of age
Secondary outcome [1] 342439 0
Local and systemic adverse events following vaccination in pregnancy. These will be collected via standard vaccine trial diary cards and in accordance with the Global Alignment of Immunization Safety Assessment in Pregnancy Guidelines and criteria.
Timepoint [1] 342439 0
30 days post vaccination
Secondary outcome [2] 342440 0
Serious vaccine-related adverse events in pregnancy and childbirth. These will be collected and assessed in accordance with the International Conference on Harmonisation Good Clinical Practice Guidelines and the Global Alignment of Immunization Safety Assessment in Pregnancy Guidelines and criteria.
Timepoint [2] 342440 0
Any time point up childbirth
Secondary outcome [3] 342441 0
Serious vaccine-related adverse events in the infant. These will be collected and assessed in accordance with the International Conference on Harmonisation Good Clinical Practice Guidelines and the Global Alignment of Immunization Safety Assessment in Pregnancy Guidelines and criteria.
Timepoint [3] 342441 0
Any time up to 12 months of age
Secondary outcome [4] 342442 0
Vaccine type antibody responses (IgGs) - Total IgG to both Protein D and vaccine-type S. pneumoniae. Serum antibodies will be measured against purified pneumococcal and H. influenzae proteins and pneumococcal polysaccharides using a multiplex bead assay.
Timepoint [4] 342442 0
Maternal at baseline and birth
Infant at birth, 6 months and 12 months of age
Secondary outcome [5] 342443 0
Infant systemic immune responses (TNF-alpha, IFN-y, IL-6, IL-13, IL-1beta) from peripherical blood mononuclear cells (PBMC). Briefly, PBMC (1x106 cells/ml) will be challenged with live NTHi or Spn (4x106 colony forming units/ml), phyto-hemagglutinin (PHA; positive control) or medium alone (baseline control). Cytokine protein, representative of innate response (TNF-a), Th1- (IFN-?) and Th2-immune response (IL-6, IL-13) and inflammation regulation (IL-1ß,) will be measured in culture supernatants at 24 or 72-hrs, as optimised previously, using a Dissociation-Enhanced Lanthanide Fluorescence Immunoassay (DELFIA™). DELFIA™ has a large dynamic range (approximately 3-30,000 pg/ml) with low background interference. Samples will be batch tested to minimise inter-assay variation.
Timepoint [5] 342443 0
At birth, 6 and 12 months of age
Secondary outcome [6] 342444 0
Nasopharyngeal carriage of Haemophilus influenzae and Streptococcus pneumoniae. Batches of swabs will be thawed and cultured on selective media. Growth of Spn (with serotypes determined), Hi and NTHi will be confirmed by standard techniques, including differentiating from H. haemolyticus
Timepoint [6] 342444 0
Maternal: baseline and birth
Infant: birth, 6 and 12 months of age

Eligibility
Key inclusion criteria
(1) Healthy Australian Indigenous or Malaysian woman;
(2) singleton pregnancy at 28-34 wks gestation;
(3) no pre-existing illness considered as a high risk to the pregnancy
(4) pregnancy deemed as high risk by attending obstetrician
(4) planned delivery at study hospitals.
Minimum age
17 Years
Maximum age
40 Years
Gender
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
(1) Contraindication or known sensitivity to PHiD-CV as per Australian guidelines
(2) immune-deficiency or suppression (primary or secondary) including hypospleenism;
(3) receipt of any pneumococcal vaccine in the 2 years prior to enrolment
(4) history of severe allergy e.g. anaphylaxis; or
(5) previously enrolled.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by phone/fax/computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The random treatment allocation will be computer-generated, stratified (permuted blocks and by site), concealed and supervised by the trial biostatistician
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Outcome assessors and data analysts will be blinded to the allocation group
Phase
Phase 2 / Phase 3
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Intention to treat analyses; planned per protocol sub-analysis
Results will be reported and presented in accordance with CONSORT guidelines.
For primary aim: The main effects of the intervention will be determined by comparing the primary outcomes: (a) proportion with any ALRI and; (b) rate of ALRI; in the first year of life between groups (PHiD-CV group vs controls). We will use odds and incidence rate ratios with logistic regression and negative binomial regression models respectively as well as determining the absolute differences between proportions (with 95%CI). We plan a preliminary analysis when 50% of the sample size for primary outcomes are available at 6-mo. We plan a 6-mo analysis (rather than at 12-mo, our RCT’s outcome) for safety reasons,

For secondary aims: We will compare differences between groups in: (i) IgGs geometric means of PD23 and serotype-specific Spn16 using Student’s T test after log transforming data (+/- maternal prevaccine levels adjustment); (ii) cytokine levels of PBMC-stimulated cells (Mann-Whitney23,47); (iii) NP Hi and Spn (vaccine and non-vaccine types separated) using Chi2 expressed as OR (95%CI).50 A Kaplan-Meier curve will be constructed for each group for time to the 1st ALRI and respiratory-related hospitalisation, log-rank test performed and hazard ratio reported (using Cox regression model).

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)
NT,QLD,SA
Recruitment hospital [1] 9876 0
Royal Darwin Hospital - Tiwi
Recruitment hospital [2] 9877 0
Toowoomba Hospital - Toowoomba
Recruitment hospital [3] 9878 0
Logan Hospital - Meadowbrook
Recruitment hospital [4] 9879 0
Caboolture Hospital - Caboolture
Recruitment hospital [5] 9880 0
Alice Springs Hospital - Alice Springs
Recruitment hospital [6] 9881 0
Mater Mother's Hospital - South Brisbane
Recruitment postcode(s) [1] 18683 0
0870 - Alice Springs
Recruitment postcode(s) [2] 18684 0
4101 - South Brisbane
Recruitment postcode(s) [3] 18681 0
4131 - Meadowbrook
Recruitment postcode(s) [4] 18680 0
4350 - Toowoomba
Recruitment postcode(s) [5] 18682 0
4510 - Caboolture
Recruitment outside Australia
Country [1] 9526 0
Malaysia
State/province [1] 9526 0
Kota Kinabalu

Funding & Sponsors
Funding source category [1] 298509 0
Government body
Name [1] 298509 0
National Health & Medical Research Council
Address [1] 298509 0
GPO Box 1421
Canberra ACT 2601
AUSTRALIA
Country [1] 298509 0
Australia
Primary sponsor type
University
Name
Menzies School of Health Research
Address
Rocklands Drive
TIWI NT 0811
Country
Australia
Secondary sponsor category [1] 297655 0
None
Name [1] 297655 0
Address [1] 297655 0
Country [1] 297655 0
Other collaborator category [1] 279917 0
University
Name [1] 279917 0
Queensland University of Technology
Address [1] 279917 0
Musk Ave
Kelvin Grove QLD 4059
Country [1] 279917 0
Australia

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 299488 0
Menzies School of Health Research Health Research Ethics Committee
Ethics committee address [1] 299488 0
Menzies School of Health Research
Rocklands Drive
TIWI NT 0811
Ethics committee country [1] 299488 0
Australia
Date submitted for ethics approval [1] 299488 0
05/03/2018
Approval date [1] 299488 0
Ethics approval number [1] 299488 0

Summary
Brief summary
We plan a parallel, single-blind multicentre RCT (with concealed allocation) to determine the efficacy of maternal PHiD-CV immunisation on infant respiratory outcomes. Our primary question is: Does vaccinating pregnant Indigenous women with PHiD-CV (compared to controls) reduce ALRI in their infants in the first year of life? Our primary hypothesis is that: Infants born to pregnant women who received PCV-HiD are at least 25% less likely likely to have ALRIs in their first year of life, compared to those who did not receive the vaccine
Trial website
Nil to date
Trial related presentations / publications
Nil to date
Public notes
Nil to date

Contacts
Principal investigator
Name 80582 0
Prof Anne Chang
Address 80582 0
Menzies School of Health Research
Rocklands Drive
TIWI NT 0810
Country 80582 0
Australia
Phone 80582 0
+61 0411 699 022
Fax 80582 0
Email 80582 0
anne.chang@menzies.edu.au
Contact person for public queries
Name 80583 0
Dr Kerry-Ann O'Grady
Address 80583 0
L7 Centre for Children's Health Research
62 Graham Street
South Brisbane QLD 4010
Country 80583 0
Australia
Phone 80583 0
+61 7 3069 7270
Fax 80583 0
Email 80583 0
kerryann.ogrady@qut.edu.au
Contact person for scientific queries
Name 80584 0
Dr Kerry-Ann O'Grady
Address 80584 0
L7 Centre for Children's Health Research
62 Graham Street
South Brisbane QLD 4010
Country 80584 0
Australia
Phone 80584 0
+61 7 3069 7270
Fax 80584 0
Email 80584 0
kerryann.ogrady@qut.edu.au

No information has been provided regarding IPD availability
Summary results
No Results