To assess the effect of alternative and reduced doses pneumococcal vaccination schedules using the 13-valent pneumococcal conjugate vaccine (PCV13, Wyeth) on the development of antibody titers directed against the different serotypes of pneumococci…
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Source
Brief title
Condition
- Bacterial infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Assessing the optimal PCV vaccination schedule: To assess the effect of the use
of pneumococcal vaccination schedules with alternative timing and reduction of
the number of vaccination doses on the serological response directed against
the different serotypes of pneumococci. This information will be used to
investigate whether a different timing or reduction of the vaccination schedule
will induce antibody responses that are equal to or better than those obtained
by the currently used vaccination schedule.
For each vaccine group, differences in serotype specific antibody
concentrations between different schedules will be analysed. The primary
endpoints are the antibody concentrations against pneumococcal polysaccharides
for each serotype at 12 months in the different study arms. GMCs and the degree
of protection (the proportion with concentration > 0.35 µg/ml) will be
determined.
Secondary outcome
Kinetics of the antibody titer: To assess the kinetics of the pneumococcal
antibody titers, in particular in the interval between the last vaccination
dose of the primairy series and the booster vaccination at 11 months. This
period coincides with the peak incidence of pneumococcal invasive disease. The
antibody concentrations of the longitudinal samples of each child will be used
to assess the kinetics.
Interference of vaccination with PCV on other vaccinations: To investigate the
possible influence of the pneumococcal vaccination on the serological responses
of the other vaccine components of the NIP which are administered
simultaneously in the other limb (DTaP-IPV-Hib). For this the antibody
concentrations (GMCs) directed to the other vaccine components of the NIP will
be determined.
Background summary
In the Netherlands nationwide pneumococcal vaccination was introduced in June
2006, with a 4-dose schedule in which children receive their vaccinations at 2,
3, 4 and 11 months of age. The reduction of the current 4-dose schedule into a
3-dose pneumococcal vaccination schedule would result in a smaller burden for
the children and would cause an annual reduction of approximately ¤ 8,000,000
in costs for the National Immunization Program (NIP). A reduced vaccination
schedule might require different vaccination moments, at a later age when the
immune system of the infant is better developed and results in a better spread
over the child*s most vulnerable period (e.g. at 3 and 5 months). The Dutch
Health Council (Gezondheidsraad) who advises the Minister of Health would like
to see more information about shorter vaccination programmes so that these can
be introduced, where possible, in the near future*. The vaccination study
described in this protocol is in full agreement with the advice of the Health
Council and also is proactive as it will be performed using the new 13-valent
pneumococcal conjugate vaccine instead of the currently used 7-valent vaccine.
Study objective
To assess the effect of alternative and reduced doses pneumococcal vaccination
schedules using the 13-valent pneumococcal conjugate vaccine (PCV13, Wyeth) on
the development of antibody titers directed against the different serotypes of
pneumococci. As an alternative 3+1 schedule we will use vaccination at 2, 4, 6
and 11 months (*USA schedule*) and compare this with 3+1 schedule currently
used in the Dutch national immunization program in which children receive
vaccination at 2, 3, 4 and 11 months. To investigate the possibility to reduce
the vaccination schedule from 3+1 to 2+1 we include schedules in which the
PCV13 will be administered at 2, 4 and 11 months (*UK schedule*) and 3, 5 and
11 months of age (*Scandinavian schedule*).
Study design
A randomized controlled parallel group trial. Children are randomly assigned to
4 groups receiving PCV13 i) at 2, 3, 4 and 11 months of age, ii) at 2, 4, 6 and
11 months of age, iii) at 2, 4 and 11 months of age and iv) at 3, 5 and 11
months of age. Children of the study groups with the reduced schedules will be
offered an extra vaccination at 24 months of age to ensure they receive the
same number of vaccinations as the children receiving the current NIP
vaccination.
During the study 4 blood samples are taken from each child enrolled in the
study at 1 month post primairy series, 8 months of age, pre-booster (11 months
of age) and one month post-booster (12 months of age). Besides the blood
samples, questionnaires including questions concerning clinical manifestations
of allergic reactions are completed. Adverse events and SAE*s are recorded in
the CRF.
Intervention
See study design
Study burden and risks
All children receive vaccinations against S. pneumonia, which may result in
some form of minor side effects. It is not expected that PCV13 will give more
side effects than PCV7, which all children currently receive in the NIP.
Immune responses of children vaccinated in different vaccination schemes will
be compared. This requires the drawing of 2 ml blood samples at various time
points during and after the vaccination series. The burden and risk associated
with the blood collection is low. The children may find the needle scary and
experience the puncture as painful. A local anaesthetic (Emla® crème, Astra
Zeneca) will be used to minimize pain. Blood collection could result in a small
bruise at the location of injection, which will disappear within a few days.
A questionnaire will be used to relate immune functions to clinical
manifestations of allergic reactions.
This study is designed to further improve pneumococcal vaccination in the
current NIP. The only possible study population is the group that would
normally participate in the NIP. All participating children will receive PCV13
vaccine that protects them against 6 more serotypes than the PCV7 vaccine
currently given in the NIP. Half of the children enrolled in the study will
receive only 3 doses of the PCV13 vaccine, one dose less than the number of
doses used in the Dutch NIP in the first year of life. However, this 2+1
schedule, , is an accepted schedule in many other countries and is now also an
accepted schedule according to the SPC of PCV7 and PCV13. Nevertheless,
children of the study groups with the reduced schedules will be offered an
extra vaccination at 24 months of age to ensure the same number of vaccination
doses are administered as to children receiving the current NIP vaccination.
Antonie van Leeuwenhoeklaan 9
3721 MA Bilthoven
NL
Antonie van Leeuwenhoeklaan 9
3721 MA Bilthoven
NL
Listed location countries
Age
Inclusion criteria
• Infants in good general health, eligible to be vaccinated according to the Dutch national vaccination program. The same health criteria apply as used in well-baby clinics when a child receives a vaccination, e.g. also children with small increases in temperature or cold are seen as children with normal health.
• The parents have to be willing and able to allow their child to participate in the trial according to the described procedures
• Presence of a signed informed consent in which the parent(s)/legally representative(s) have given written informed consent after receiving oral and written information (signature from one parent in case of an orphan, or single-parent family).
Exclusion criteria
Any of the following criteria will exclude a volunteer from participation, at start of the study:
• Children elegible for the Hepatitis B vaccination
• Previous Prevenar and DTaP-IPV-Hib vaccination
• Present evidence of serious disease(s) demanding immunosuppressive medical treatment, like cytostatics and prednisolons, that might interfere with the results of the study within 3 months
• Any known primary or secondary immunodeficiency
• Vaccination with any vaccine other than those used in the RVP within a month before the blood sampling
• Bleeding disorders
• Premature birth (<37 weeks);Delay criteria
• In case of fever (>38.5 oC) the vaccination will be postponed
• In case a child is having fever (>38 oC) within 2 days before blood sampling which can interfere with the cellular immune responses at that time, another appointment for blood sampling will be made
Design
Recruitment
Medical products/devices used
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In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2009-014315-12-NL |
| CCMO | NL28918.000.09 |