Effect of 2 versus 3 pneumococcal conjugate vaccinations Prevnar on nasopharyngeal carriage, transmission and herd immunity; a randomized, controlled study.

ISRCTN	ISRCTN25571720
DOI	https://doi.org/10.1186/ISRCTN25571720
ClinicalTrials.gov number	NCT00189020
Secondary identifying numbers	MINOES 01, STEG R05 008

Submission date: 20/12/2005
Registration date: 20/12/2005
Last edited: 31/05/2019

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Study website

Contact information

Prof E.A.M. Sanders
Scientific

University Medical Center Utrecht
Department of Pediatric Immunology
HP 06.063.0
P.O. Box 85090
Lundlaan 6
Utrecht
3508 AB
Netherlands

Phone	+31 (0)30 2504000
Email	l.sanders@umcutrecht.nl

Study information

Study design	Randomised controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Not specified
Study type	Not Specified
Scientific title	Effect of 2 versus 3 pneumococcal conjugate vaccinations Prevnar on nasopharyngeal carriage, transmission and herd immunity; a randomized, controlled study.
Study acronym	MINOES
Study objectives	Study hypotheses amended as of 22/05/2007: 1. Two vaccinations with 7-valent conjugate vaccine before six months of age will protect against invasive pneumococcal disease in the first 18 to 24 months of life 2. Two vaccinations at 2 and 4 months of age without a booster vaccination at 11 months will have less effect on vaccine-type pneumococcal carriage reduction and therefore also herd-immunity and respiratory tract infections but also less pneumococcal replacement by non-vaccine types and other potentially pathogenic bacteria 3. Anti-pneumococcal antibody development after two vacinations with 7-valent conjugate vacine before six months of age and revaccination at 24 months of age will be equal or better compared with antibody development after two vaccination before six months of age followed by booster vaccination at 11 and 24 months of age. Later vaccination will improve long term protection Previous study hypothesis: 1. Two vaccinations before the age of 6 months with the pneumococcal conjugate vaccine Prevnar in infants will protect the children against invasive pneumococcal disease. 2. Two vaccinations at 2 and 4 months of age without a booster vaccination at 11 months will have less effect on vaccine-type pneumococcal carriage reduction and therefore also herd-immunity and respiratory tract infections but also less pneumococcal replacement by non-vaccine types and other potentially pathogenic bacteria.
Ethics approval(s)	Approval received from the local medical ethics board (Stichting Therapeutische Evaluatie Geneesmiddelen [STEG], acknowledged by the Centrale Commissie Mensgebonden Onderzoek [CCMO], The Netherlands) on the 21st June 2005 (ref: STEG R05.008, version 6). First and second amendment (collection of saliva for immunological analysis and extension microbiology research of collected nasopharyngeal swabs in subgroups of children) approved on the 11th September 2006. Third amendment (addition of booster vaccination at 24 months and blood sampling) approved on the 2nd March 2007 (ref: STEG R05-008, MINOES version 8 dd february 2007).
Health condition(s) or problem(s) studied	Invasive pneumococcal disease, Respiratory tract infection. Added as of 22/05/2007: Change in: nasopharyngeal carriage after reduced doses 7-valent conjugate vaccine, antipneumococcal antibody development, family transmission of pneumococci
Intervention	Three groups of each 333 newborns: Group I: Prevnar at age 2 and 4 months Group II: Prevnar at age 2, 4 and 11 months Group III: Prevnar at age 24 months Amendment made as of 22/05/2007: Groups I and II will receive booster vaccination 7-valent conjugate vaccine at 24 months of age.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Pneumococcal conjugate vaccine Prevnar
Primary outcome measure	Pneumococcal nasopharyngeal carriage before 2 months of age, and at 6, 12, 18 and 24 months of age in vaccinated children (groups I and II) and controls (group III), and NP pneumococcal carriage of siblings and parents/caregivers when the baby is 12 and 24 months of age (herd immunity).
Secondary outcome measures	1. Determination of pneumococcal (vaccine and non-vaccine serotypes) colonization of infants in the Netherlands before introduction of Prevnar in the National Vaccination Program (group III) 2. Evaluation of replacing pneumococcal serotypes after Prevnar vaccinations 3. Influence of Prevnar vaccinations on other colonizing bacterial species like Staphylococcus, H. influenzae, M. catarrhalis and Streptococcus 4. Anti pneumococcal antibody levels at 12 and 24 months after 2 doses as compared to 2+1 Prevnar vaccinations 5. Relation between invasive pneumococcal disease and pneumococcal colonization in the Netherlands 6. Evaluation of potential reduction of physician-diagnosed acute otitis media and lower respiratory tract infections after pneumococcal conjugate vaccinations Added as of 22/05/2007: 7. Comparison of anti-pneumococcal antibody levels after vaccinations at 2, 4 and 24 months, at 2, 4, 11 and 24 months and after primo-vaccination at 24 months of age in subgroups of 80 children of groups I, II and III 8. Comparison of B-memory cells after vaccination at 24 months of age after vaccination schemes of groups I, II and III
Overall study start date	20/06/2005
Completion date	01/03/2008

Eligibility

Participant type(s)	Patient
Age group	Neonate
Sex	Both
Target number of participants	1000
Total final enrolment	1003
Key inclusion criteria	1000 healthy newborns (and family members) who will receive childhood vaccinations according to the national vaccination program, starting at 2 months of age.
Key exclusion criteria	Exclusion from the national vaccination program because of the presence of a medical condition requiring treatment that can interfere with the results of vaccinations, known of suspected allergy to components of the vaccine, known or suspected immunodeficiency disease other than IgA or IgG-subclass deficiency, previous treatment with plasma or immunoglobulins, previous vaccinations other than hepatitis B vaccinations, coagulations disorders
Date of first enrolment	20/06/2005
Date of final enrolment	01/03/2008

Locations

Countries of recruitment

Netherlands

Study participating centre

University Medical Center Utrecht

Utrecht
3508 AB
Netherlands

Sponsor information

University Medical Centre Utrecht (UMCU) (Netherlands)
University/education

PO Box 85500
Utrecht
3508 GA
Netherlands

Website	http://www.umcutrecht.nl/zorg/
"ROR"	https://ror.org/04pp8hn57

Funders

Funder type

Government

The Netherlands Ministry of Health, Welfare and Sport (The Netherlands)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/09/2011	31/05/2019	Yes	No
Results article	results	01/12/2014	31/05/2019	Yes	No
Results article	results	01/08/2014	31/05/2019	Yes	No
Results article	results	02/12/2013	31/05/2019	Yes	No
Results article	results	01/12/2011	31/05/2019	Yes	No
Results article	results	01/02/2014	31/05/2019	Yes	No
Results article	results	08/07/2009	31/05/2019	Yes	No
Results article	results	08/09/2010	31/05/2019	Yes	No

Editorial Notes

31/05/2019: The following changes were made:
1. Publication reference added.
2. Total final enrolment added.
3. Clinicaltrials.gov number added.