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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01735084




Registration number
NCT01735084
Ethics application status
Date submitted
15/11/2012
Date registered
28/11/2012
Date last updated
25/03/2020

Titles & IDs
Public title
Using Pneumococcal Vaccines in Combination for Maximum Protection From Ear and Lung Infections in First 3 Years of Life
Scientific title
Pneumococcal Conjugate Vaccine (PCV) Schedules for the Northern Territory (NT): Randomised Controlled Trial of Booster Vaccines to Broaden and Strengthen Protection From Invasive and Mucosal Infections.
Secondary ID [1] 0 0
1046999
Universal Trial Number (UTN)
Trial acronym
PREV-IX_B
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Otitis Media 0 0
Febrile Illness 0 0
Cough 0 0
Lower Respiratory Tract Infection 0 0
Upper Respiratory Tract Infection 0 0
Condition category
Condition code
Infection 0 0 0 0
Studies of infection and infectious agents
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Sexually transmitted infections
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Ear 0 0 0 0
Other ear disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Prevenar13
Treatment: Other - Synflorix

Experimental: Prevenar13 - The booster dose of Prevenar13 is 0.5 mL given intramuscularly only, with care to avoid injection into or near nerves and blood vessels. The preferred sites are anterolateral aspect of the thigh (vastus lateralis muscle) in infants or the deltoid muscle of the upper arm in young children.

Experimental: Synflorix - The booster vaccination schedule consists of one dose of 0.5 ml with an interval of at least 1 month between doses.


Treatment: Other: Prevenar13
The vaccine is a ready to use homogeneous white suspension for intramuscular injection, supplied as a pre-filled syringe.

Active ingredients

Each 0.5 mL dose contains:

2.2 µg of pneumococcal purified capsular polysaccharides for serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F and 23F 4.4 µg of pneumococcal purified capsular polysaccharides for serotype 6B. Each serotype is individually conjugated to non-toxic diphtheria CRM197 protein and adsorbed on aluminium phosphate (0.565 mg).

Treatment: Other: Synflorix
The 10-valent vaccine contains 1 µg of purified capsular polysaccharide of pneumococcal serotypes 1, 5, 6B, 7F, 9V, 14, and 23F conjugated to protein D, 3 µg of serotype 4 conjugated to protein D, 3 µg of serotype 18C conjugated to tetanus toxoid and 3 µg of serotype 19F conjugated to diphtheria toxoid.
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Immune response
Timepoint [1] 0 0
At 18 months of age
Secondary outcome [1] 0 0
Nasopharyngeal carriage
Timepoint [1] 0 0
At 12, 18 and 36 months of age
Secondary outcome [2] 0 0
Otitis media
Timepoint [2] 0 0
At 12, 18 and 36 months of age

Eligibility
Key inclusion criteria
* Australian Indigenous infant who was a participant in PREV-IX_COMBO trial of primary course pneumococcal conjugate vaccines, age at least 2 months post final dose of primary course. Signed informed consent.
Minimum age
9 Months
Maximum age
3 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
* adverse reaction to Prevenar13 or Synflorix

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/03/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
3/10/2019
Sample size
Target
Accrual to date
Final
261
Recruitment in Australia
Recruitment state(s)
NT
Recruitment hospital [1] 0 0
Menzies School of Health Research - Darwin
Recruitment postcode(s) [1] 0 0
0810 - Darwin

Funding & Sponsors
Primary sponsor type
Other
Name
Menzies School of Health Research
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
National Health and Medical Research Council, Australia
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
HYPOTHESES:

1. That infants receiving PHiD-CV10 as a booster at 12 months of age, compared to controls having no PHiD-CV10 booster (i.e. standard PCV13), will have higher HiD antibody levels, lower carriage of NTHi, and less tympanic membrane perforation at 18 and 36 months of age.
2. That infants receiving PCV13 as a booster at 12 months of age, compared to controls having no PCV13 (i.e. PHiD-CV10 booster) will have higher antibody levels to serotypes 3, 6A and 19A, less carriage of these serotypes, and less tympanic membrane perforation at 18 and 36 months of age.
Trial website
https://clinicaltrials.gov/study/NCT01735084
Trial related presentations / publications
Williams SR, Mernagh PJ, Lee MH, Tan JT. Changing epidemiology of invasive pneumococcal disease in Australian children after introduction of a 7-valent pneumococcal conjugate vaccine. Med J Aust. 2011 Feb 7;194(3):116-20. doi: 10.5694/j.1326-5377.2011.tb04192.x.
Miller E, Andrews NJ, Waight PA, Slack MP, George RC. Effectiveness of the new serotypes in the 13-valent pneumococcal conjugate vaccine. Vaccine. 2011 Nov 15;29(49):9127-31. doi: 10.1016/j.vaccine.2011.09.112. Epub 2011 Oct 5.
Weinberger DM, Malley R, Lipsitch M. Serotype replacement in disease after pneumococcal vaccination. Lancet. 2011 Dec 3;378(9807):1962-73. doi: 10.1016/S0140-6736(10)62225-8. Epub 2011 Apr 12.
Leach AJ, Morris PS, Mackenzie G, McDonnell J, Balloch A, Carapetis J, Tang M. Immunogenicity for 16 serotypes of a unique schedule of pneumococcal vaccines in a high-risk population. Vaccine. 2008 Jul 23;26(31):3885-91. doi: 10.1016/j.vaccine.2008.05.012. Epub 2008 May 27.
Black S, Shinefield H, Fireman B, Lewis E, Ray P, Hansen JR, Elvin L, Ensor KM, Hackell J, Siber G, Malinoski F, Madore D, Chang I, Kohberger R, Watson W, Austrian R, Edwards K. Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children. Northern California Kaiser Permanente Vaccine Study Center Group. Pediatr Infect Dis J. 2000 Mar;19(3):187-95. doi: 10.1097/00006454-200003000-00003.
Hare KM, Grimwood K, Leach AJ, Smith-Vaughan H, Torzillo PJ, Morris PS, Chang AB. Respiratory bacterial pathogens in the nasopharynx and lower airways of Australian indigenous children with bronchiectasis. J Pediatr. 2010 Dec;157(6):1001-5. doi: 10.1016/j.jpeds.2010.06.002. Epub 2010 Jul 24.
Vesikari T, Karvonen A, Korhonen T, Karppa T, Sadeharju K, Fanic A, Dieussaert I, Schuerman L. Immunogenicity of 10-valent pneumococcal nontypeable Haemophilus Influenzae Protein D Conjugate Vaccine when administered as catch-up vaccination to children 7 months to 5 years of age. Pediatr Infect Dis J. 2011 Aug;30(8):e130-41. doi: 10.1097/INF.0b013e31821d1790.
Clucas DB, Carville KS, Connors C, Currie BJ, Carapetis JR, Andrews RM. Disease burden and health-care clinic attendances for young children in remote aboriginal communities of northern Australia. Bull World Health Organ. 2008 Apr;86(4):275-81. doi: 10.2471/blt.07.043034.
Leach AJ, Morris PS, Mathews JD; Chronic Otitis Media Intervention Trial - One (COMIT1) group. Compared to placebo, long-term antibiotics resolve otitis media with effusion (OME) and prevent acute otitis media with perforation (AOMwiP) in a high-risk population: a randomized controlled trial. BMC Pediatr. 2008 Jun 2;8:23. doi: 10.1186/1471-2431-8-23.
Simell B, Nurkka A, Lahdenkari M, Givon-Lavi N, Kayhty H, Dagan R, Jokinen J. Association of serotype-specific antibody concentrations and functional antibody titers with subsequent pneumococcal carriage in toddlers immunized with a 9-valent pneumococcal conjugate vaccine. Clin Vaccine Immunol. 2012 Jan;19(1):96-9. doi: 10.1128/CVI.05369-11. Epub 2011 Nov 9.
Leach AJ, Morris PS, McCallum GB, Wilson CA, Stubbs L, Beissbarth J, Jacups S, Hare K, Smith-Vaughan HC. Emerging pneumococcal carriage serotypes in a high-risk population receiving universal 7-valent pneumococcal conjugate vaccine and 23-valent polysaccharide vaccine since 2001. BMC Infect Dis. 2009 Aug 4;9:121. doi: 10.1186/1471-2334-9-121.
Prymula R, Kriz P, Kaliskova E, Pascal T, Poolman J, Schuerman L. Effect of vaccination with pneumococcal capsular polysaccharides conjugated to Haemophilus influenzae-derived protein D on nasopharyngeal carriage of Streptococcus pneumoniae and H. influenzae in children under 2 years of age. Vaccine. 2009 Dec 10;28(1):71-8. doi: 10.1016/j.vaccine.2009.09.113. Epub 2009 Oct 8.
Prymula R, Peeters P, Chrobok V, Kriz P, Novakova E, Kaliskova E, Kohl I, Lommel P, Poolman J, Prieels JP, Schuerman L. Pneumococcal capsular polysaccharides conjugated to protein D for prevention of acute otitis media caused by both Streptococcus pneumoniae and non-typable Haemophilus influenzae: a randomised double-blind efficacy study. Lancet. 2006 Mar 4;367(9512):740-8. doi: 10.1016/S0140-6736(06)68304-9.
Leach AJ, Wilson N, Arrowsmith B, Beissbarth J, Mulholland EK, Santosham M, Torzillo PJ, McIntyre P, Smith-Vaughan H, Chatfield MD, Lehmann D, Binks M, Chang AB, Carapetis J, Krause V, Andrews R, Snelling T, Skull SA, Licciardi PV, Oguoma VM, Morris PS. Immunogenicity, otitis media, hearing impairment, and nasopharyngeal carriage 6-months after 13-valent or ten-valent booster pneumococcal conjugate vaccines, stratified by mixed priming schedules: PREVIX_COMBO and PREVIX_BOOST randomised controlled trials. Lancet Infect Dis. 2022 Sep;22(9):1374-1387. doi: 10.1016/S1473-3099(22)00272-9. Epub 2022 Jun 27.
Oguoma VM, Wilson N, Mulholland K, Santosham M, Torzillo P, McIntyre P, Smith-Vaughan H, Balloch A, Chatfield M, Lehmann D, Binks MJ, Chang A, Carapetis J, Krause V, Andrews R, Snelling T, Licciardi P, Morris P, Leach AJ. 10-Valent pneumococcal non-typeable H. influenzae protein D conjugate vaccine (PHiD-CV10) versus 13-valent pneumococcal conjugate vaccine (PCV13) as a booster dose to broaden and strengthen protection from otitis media (PREVIX_BOOST) in Australian Aboriginal children: study protocol for a randomised controlled trial. BMJ Open. 2020 May 24;10(5):e033511. doi: 10.1136/bmjopen-2019-033511.
Public notes

Contacts
Principal investigator
Name 0 0
Amanda J Leach, PhD
Address 0 0
Menzies School of Health Research
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01735084