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Trial registered on ANZCTR


Registration number
ACTRN12612000034831
Ethics application status
Approved
Date submitted
6/01/2012
Date registered
9/01/2012
Date last updated
16/10/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
CHiRRP: Combating Haemophilus influenzae Related Respiratory Pathology
Scientific title
A multi-centre, double-blind, randomised controlled trial to evaluate the efficacy of 10 valent-pneumococcal-Protein D conjugate vaccine compared to quadrivalent (ACYW135) meningococcal conjugate vaccine in reducing respiratory exacerbations in children aged greater than or equal to 18 months with suppurative lung disease.
Secondary ID [1] 279670 0
Nil
Universal Trial Number (UTN)
U1111-1126-8627
Trial acronym
CHiRRP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Suppurative lung disease (excluding cystic fibrosis) 285490 0
Condition category
Condition code
Respiratory 285679 285679 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
10valent pneumococcal - Protein D conjugate vaccine (10vPHiD), 0.5ml intramuscular injection, 2 doses, 2 months apart
Intervention code [1] 283961 0
Prevention
Intervention code [2] 283974 0
Treatment: Drugs
Comparator / control treatment
Quadrivalent (Men ACYW135) meningococcal conjugate vaccine: 0.5ml intramuscular injection, 2 doses, 2 months apart
Control group
Active

Outcomes
Primary outcome [1] 286218 0
Respiratory exacerbation: An increase in sputum volume or purulence, or greater than 3-days of change in cough (>20% increase in cough score (validated scale) or type [dry to wet]). Participants will complete daily cough diaries for the duration of the study
Timepoint [1] 286218 0
12 months post dose 2 of vaccine
Secondary outcome [1] 295399 0
Nasopharyngeal carriage of NTHi and vaccine type Streptococcus pneumoniae: specimens collected using cotton tip swab and analysed at the Menzies School of Health Research laboratory using both PCR and culture methodologies
Timepoint [1] 295399 0
2 months post dose 1 and six and 12 months following the second dose of study vaccine
Secondary outcome [2] 295400 0
Serum antibody to Protein D, related NTHi proteins (P4 and P6) and to vaccine type pneumococcal serotypes: venus blood will be collected at study timepoints detailed below and analysed at the Telethon Institute for Child Health Research laboratory.
Timepoint [2] 295400 0
2 months post dose 1 and six and 12 months following the second dose of study vaccine expressed as anti-PD antibody geometric mean titres.
Secondary outcome [3] 295401 0
Safety: The safety and reactogenicity of vaccination (local and systemic reactions) and serious adverse events. Adverse event data will be collected using diary cards and via active surveillance for SAEs.

Local reactions to be assessed include pain, redness and swelling at the injection site.

Systemic reactions include fever, malaise, rash, nausea/vomiting, myalgia, nause/vomiting, diarrhoea
Timepoint [3] 295401 0
Day 7 and day 30 post each dose of vaccine . Serious adverse events will be monitored over the entire active study period.
Secondary outcome [4] 295402 0
4. Serum antibody to pneumococcal serotypes contained in the 10vPHiD vaccine (1, 5, 6B, 7F, 9V, 14, 23F, 4, 18C and 19F) expressed as anti-Pn antibody geometric mean titres.
Timepoint [4] 295402 0
2 months post dose 1 and six and 12 months following the second dose of study vaccine
Secondary outcome [5] 305488 0
Mucosal antibody responses to Protein D, related NTHi proteins (P4 and P6) and vaccine type pneumococcal serotypes. Salivary specimens will be collected and analysed at the Telethon Institute for Child Health Research at the University of Western Australia
Timepoint [5] 305488 0
2 months post dose 1 and six and 12 months following the second dose of study vaccine

Eligibility
Key inclusion criteria
1. Child aged greater than or equal to 18 months and < 18 years with CSLD. The case definitions for CSLD are: a) CSLD: a clinical syndrome where there are symptoms indicating chronic endobronchial suppuration with or without HRCT evidence of radiological bronchiectasis. The main feature of the clinical syndrome is recurrent (3 or more episodes/yr) chronic (>4 weeks) wet cough responding to antibiotics b) BE: confirmed by chest HRCT scan in last 5 years c) 3 or more episodes of Protracted Bacterial Bronchitis. Protracted bacterial bronchitis is defined as the presence of isolated chronic (>4 weeks) of wet/moist cough that resolves with antibiotics in the absence of pointers suggestive of an alternative specific cause of cough. 2. Receipt of meningococcal C conjugate monovalent vaccine at least 6 months prior to enrolment. 3 Provision of written informed consent from parent/guardian (assent if child aged greater than or equal to10 years) 4. Parent/child willing and able to meet the requirements of the protocol 5. Not planning to move from the study area in the 12 months following enrolment.
6. At least 2 respiratory exacerbations in the preceding 18 months
Minimum age
18 Months
Maximum age
18 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Prior vaccination with PHiD-CV vaccine; contraindication to PHiD-CV and/or quadrivalent meningococcal conjugate vaccine as per the Australian Immunisation Handbook and product information sheets;10 known hypersensitivity to any component of the vaccines; confirmed or suspected immunosuppressive condition or immunodeficiency disorder; current (or within 90 days prior to receiving study vaccine) or planned (during the active study period) immunosuppressive therapy, including systemic corticosteroids (greater than14 days); administration of immunoglobulins and/or blood products with 90 days prior to receiving study vaccine, or planned administration of such products during the study period.

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)
Potentially eligible children will be identified from the patient lists of the respiratory specialist departments and clinics at each of the participating study sites. The parents/guardians will be given a brief explanation of the study and provided with an information flyer and plain language statement to read at home. The attending specialist will obtain consent for the parent/guardian to be contacted by research staff to determine willingness to participate in the study. If parents/guardians are willing to discuss the study, they will be contacted by study staff for an interview over the phone to go through the study in detail. If they are interested in participating in the study, an appointment will be made for the first study visit.

Subjects will be assigned a unique subject number when written informed consent is provided. This number will identify the participant until randomisation. Once eligibility has been confirmed, a unique treatment number will be assigned at randomisation. This number will correspond to a vaccine pack which will be used to identify the participant for the duration of the study.

Group allocation and vaccine code assignments will be maintained in secure electronic and paper files that are inaccessible to all investigators, study staff and participants. The independent statistician will keep the randomisation code on file and emergency code break envelopes will be kept securely at QCMRI for use in case of an emergency.

Vaccines will be repackaged and labelled at a Therapeutic Goods Administration approved Good Manufacturing Practice facility to appear identical to study personnel and participants. The study vaccines will be packed according to the randomisation code.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A study statistician not directly involved in the analysis of study results will prepare the study randomisation code in a statistical database. A randomisation blocking scheme will be used to ensure that balance between the two treatment groups is maintained. Participants will be randomised to Group A or B (1:1 allocation), using computer generated random permuted block sizes. Randomisation will be stratified by age (< 6yrs and greater than or equal to 6 yrs), and PBB vs other CSLD (4 strata). Six years is considered the age at which spirometry can be reliably performed in children. Treatment allocation will be determined using an internet based randomisation system administered by a statistician independent to the study.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Data analysis is complete
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Participant recruitment difficulties
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)
NSW,QLD,WA,VIC
Recruitment hospital [1] 12189 0
The Royal Childrens Hospital - Parkville
Recruitment postcode(s) [1] 24358 0
3054 - Carlton North

Funding & Sponsors
Funding source category [1] 284453 0
Government body
Name [1] 284453 0
NHMRC
Address [1] 284453 0
Level 1
16 Marcus Clarke Street
Canberra ACT 2601
Country [1] 284453 0
Australia
Primary sponsor type
University
Name
University of Queensland
Address
University of Queensland
Brisbane QLD 4072
Country
Australia
Secondary sponsor category [1] 283379 0
University
Name [1] 283379 0
National Centre for Immunisation Research & Surveillance
Address [1] 283379 0
University of Sydney
The Children's Hospital
Cnr Hawkesbury Rd & Hainsworth St,
Westmead NSW 2145
Country [1] 283379 0
Australia
Secondary sponsor category [2] 283380 0
Hospital
Name [2] 283380 0
Princess Margaret Hospital for Children
Address [2] 283380 0
Perth WA
Country [2] 283380 0
Australia
Secondary sponsor category [3] 283381 0
University
Name [3] 283381 0
Menzies School of Health Research, Charles Darwin University
Address [3] 283381 0
Rocklands Drive
TIWI NT 0810
Country [3] 283381 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 286430 0
Ethics committee address [1] 286430 0
Ethics committee country [1] 286430 0
Date submitted for ethics approval [1] 286430 0
01/02/2012
Approval date [1] 286430 0
15/03/2012
Ethics approval number [1] 286430 0

Summary
Brief summary
Chronic suppurative lung diseases in children are major causes of morbidity and mortality worldwide, particularly in disadvantaged populations. Repeated infections in childhood contribute to poor lung health in adulthood. The most common organism associated with infection is non-typeable Haemophilus influenzae (NTHi). This study aims to determine whether a vaccine against NTHi (10v-PHiD) can reduce repeated respiratory infections in children. We will be comparing the number of respiratory exacerbations in the 12 months following vaccinated between children with chronic lung disease vaccinated with 10vPHiD and children who received a meningococcal vaccine (control vaccine).
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 33585 0
Dr Kerry-Ann
Address 33585 0
Centre for Children's Health Research
L7, 62 Graham Street
South Brisbane QLD 4010
Country 33585 0
Australia
Phone 33585 0
+61 7 3069 7270
Fax 33585 0
Email 33585 0
kerryann.ogrady@qut.edu.au
Contact person for public queries
Name 16832 0
Dr Dr Kerry-Ann O'Grady
Address 16832 0
Centre for Children's Health Research
L7, 62 Graham Street
South Brisbane QLD 4010
Country 16832 0
Australia
Phone 16832 0
+61 7 3069 7270
Fax 16832 0
Email 16832 0
kerryann.ogrady@qut.edu.au
Contact person for scientific queries
Name 7760 0
Dr Dr Kerry-Ann O'Grady
Address 7760 0
Centre for Children's Health Research
L7, 62 Graham Street
South Brisbane QLD 4010
Country 7760 0
Australia
Phone 7760 0
+61 7 3069 7270
Fax 7760 0
Email 7760 0
kerryann.ogrady@qut.edu.au

No data has been provided for results reporting
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary