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Pneumococcal Vaccines Early and in Combination (PREVIX_COMBO)

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified April 2015 by Menzies School of Health Research.
Recruitment status was:  Recruiting
ClinicalTrials.gov Identifier:
First Posted: August 4, 2010
Last Update Posted: April 9, 2015
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Menzies School of Health Research
The purpose of this study is to determine whether an early schedule of a combination of three doses of PHiD-CV and one dose of PCV13, is superior to three doses of either PCV13 or PHiD-CV.

Condition Intervention Phase
Otitis Media Drug: Synflorix Drug: Prevenar13 Drug: COMBO Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: A Randomised Controlled Trial of Pneumococcal Conjugate Vaccines Synflorix and Prevenar13 in Sequence or Alone in High-risk Indigenous Infants (PREV-IX_COMBO): Immunogenicity, Carriage and Otitis Media Outcomes

Resource links provided by NLM:

Further study details as provided by Menzies School of Health Research:

Primary Outcome Measures:
  • Immunogenicity [ Time Frame: 7 months of age ]
    At 7 months of age, the overall and serotype specific (particularly serotype 19A and HiD) a IgG Geometric Mean Concentration (GMC) b proportion of children with IgG GMC above threshold (0.35 microg/mL)

Secondary Outcome Measures:
  • nasopharyngeal carriage [ Time Frame: 7 months of age ]
    At 7 months of age, the proportion of children with any carriage of serotype 19A pneumococci

  • nasopharyngeal carriage [ Time Frame: 7 months of age ]
    At 7 months of age, the proportion of children with any carriage of non-capsular H. influenzae.

  • otitis media [ Time Frame: 7 months of age ]
    At 7 months of age, the proportion of children with any otitis media.

Estimated Enrollment: 425
Study Start Date: August 2011
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Synflorix Drug: 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.
Other Name: PHiD-CV
Active Comparator: Prevenar13 Drug: 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). CRM197 is a nontoxic variant of diphtheria toxin isolated from cultures of Corynebacterium diphtheriae strain C7 (β197) grown in a casamino acids and yeast extract-based medium.

Other Name: PCV13
Experimental: COMBO
COMBINATION SCHEDULE of comparator vaccine 1 and comparator vaccine 2 Synflorix at 1,2,4 months then Prevenar13 at 6 months.
COMBINATION SCHEDULE of vaccine 1 and vaccine 2: Synflorix (PHiD-CV) at 1,2,4 months then Prevenar13 (PCV13) at 6 months of age.
Other Name: Combination schedule

Detailed Description:

Aboriginal children in the Northern Territory (NT) have high rates of otitis media caused by non-capsular H. influenzae (NCHi) and pneumococci. Pneumococcal conjugate vaccine has effectively reduced disease caused by the 7 serotypes. Rates of non-vaccine serotype otitis media (OM), particularly 19A is increasing, and NCHi continues to be a major pathogen in perforations. Parallels with pneumonia are highly probable in this population. Vaccines with expanded and early age protection are needed.

In early 2009 GSK's pneumococcal H. influenzae protein D conjugate vaccine (PHiD-CV) was licensed in Australia. Compared to the current vaccine, 7PCV, this vaccine offers protection from pneumococcal serotypes 1, 5, 7F as well as NCHi (which is a primary pathogen of OM, and possibly pneumonia). However by 2010, a new generation of Wyeth's 7PCV, PCV13 will also be licensed in Australia. Compared to PHiD-CV this vaccine offers protection from additional serotypes 3, 6A and 19A, however it does not offer protection from NCHi infection. There is no empirical evidence to suggest that either vaccine will have superior clinical efficacy for otitis media or pneumonia in high-risk children. The novel combination strategy proposed for this trial has the potential to provide the best of both vaccines.


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   up to 38 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

Indigenous infants

  • 4 to 6 weeks of age
  • Living in remote communities that have provided signed Expressions of Interest in participating in PREV-IX_COMBO trial
  • Intend to remain in their community until their baby is 7 months of age
  • Eligible for routine vaccinations.

Exclusion Criteria:

  • Prior adverse reaction to pneumococcal conjugate vaccines according to Australian Immunization Handbook.
  • Gestational age < 32 weeks
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01174849

Contact: Amanda J Leach, PhD +61 8 89228649 amanda.leach@menzies.edu.au

Australia, Northern Territory
Menzies School of Health Research Recruiting
Darwin, Northern Territory, Australia, 0811
Contact: Amanda J Leach, PhD    +61 8 89228196 ext 28649    amanda.leach@menzies.edu.au   
Principal Investigator: Amanda J Leach, PhD         
Sponsors and Collaborators
Menzies School of Health Research
Principal Investigator: Amanda J Leach, PhD Menzies School of Health Research
  More Information

Morris PS, Leach AJ, Silberberg P, Mellon G, Wilson C, Hamilton E, Beissbarth J. Otitis media in young Aboriginal children from remote communities in Northern and Central Australia: a cross-sectional survey. BMC Pediatr. 2005 Jul 20;5:27.
Leach AJ, Morris PS. The burden and outcome of respiratory tract infection in Australian and aboriginal children. Pediatr Infect Dis J. 2007 Oct;26(10 Suppl):S4-7.
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.
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.
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.
Mackenzie GA, Carapetis JR, Leach AJ, Morris PS. Pneumococcal vaccination and otitis media in Australian Aboriginal infants: comparison of two birth cohorts before and after introduction of vaccination. BMC Pediatr. 2009 Feb 19;9:14. doi: 10.1186/1471-2431-9-14.
Leach AJ, Boswell JB, Asche V, Nienhuys TG, Mathews JD. Bacterial colonization of the nasopharynx predicts very early onset and persistence of otitis media in Australian aboriginal infants. Pediatr Infect Dis J. 1994 Nov;13(11):983-9.
Smith-Vaughan H, Byun R, Nadkarni M, Jacques NA, Hunter N, Halpin S, Morris PS, Leach AJ. Measuring nasal bacterial load and its association with otitis media. BMC Ear Nose Throat Disord. 2006 May 10;6:10.
Hare KM, Morris P, Smith-Vaughan H, Leach AJ. Random colony selection versus colony morphology for detection of multiple pneumococcal serotypes in nasopharyngeal swabs. Pediatr Infect Dis J. 2008 Feb;27(2):178-80. doi: 10.1097/INF.0b013e31815bb6c5.
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.
Roche PW, Krause V, Cook H, Barralet J, Coleman D, Sweeny A, Fielding J, Giele C, Gilmour R, Holland R, Kampen R; Enhanced Invasive Pneumococcal Disease Surveillance Working Group, Brown M, Gilbert L, Hogg G, Murphy D; Pneumococcal Working Party of the Communicable Diseases Network Australia. Invasive pneumococcal disease in Australia, 2006. Commun Dis Intell Q Rep. 2008 Mar;32(1):18-30.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Menzies School of Health Research
ClinicalTrials.gov Identifier: NCT01174849     History of Changes
Other Study ID Numbers: 605810
ACTRN12610000544077 ( Registry Identifier: Australia New Zealand Clinical Trials Registry (ANZCTR) )
First Submitted: August 2, 2010
First Posted: August 4, 2010
Last Update Posted: April 9, 2015
Last Verified: April 2015

Keywords provided by Menzies School of Health Research:
otitis media
pneumococcal vaccines
randomised controlled trial
high-risk children

Additional relevant MeSH terms:
Otitis Media
Ear Diseases
Otorhinolaryngologic Diseases
Heptavalent Pneumococcal Conjugate Vaccine
Immunologic Factors
Physiological Effects of Drugs

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