Condition category
Nervous System Diseases
Date applied
15/05/2019
Date assigned
21/05/2019
Last edited
20/05/2019
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Meningococcal group B bacteria are a serious cause of life-threatening infections worldwide, including meningitis and blood poisoning. Developing a vaccine against the most common cause (type B) has been a priority but technically very difficult. Because the disease is so rare it has not been possible to carry out the standard type of study (randomised controlled trial) to prove that these vaccines actually protect people against the disease, instead licensure was based on the pattern of antibodies produced and predicted coverage of the commonest strains of Meningococcal disease.

Who can participate?
All children and adolescents diagnosed with invasive meningococcal disease in Portugal between October 2014 and March 2019 inclusive will be eligible for inclusion. For each case, 2 - 4 age and location matched controls will be identified.

What does the study involve?
Examination of medical records including immunisation history of cases and matched controls

What are the possible benefits and risks of participating?
None

Where is the study run from?
Coimbra, Portugal with participation of multiple hospitals in Portugal

When is the study starting and how long is it expected to run for?
April 2018 to September 2019

Who is funding the study?
The investigators and clinicians providing data are undertaking the study as part of their professional duties. No external funding has been sought or obtained.

Who is the main contact?
1. Dr Robin Marlow,
robin.marlow@bristol.ac.uk
2. Prof. Fernanda Rodrigues,
rodriguesfmp@gmail.com
3. Prof. Adam Finn,
adam.finn@bristol.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Dr Robin Marlow

ORCID ID

http://orcid.org/0000-0002-3192-3102

Contact details

Level 6
BRI Education Centre
Bristol
BS2 8AE
United Kingdom
0117 342 0172
robin.marlow@bristol.ac.uk

Type

Scientific

Additional contact

Prof Fernanda Rodrigues

ORCID ID

http://orcid.org/0000-0002-5820-5215

Contact details

Centro Hospitalar e Universitário de Coimbra - Hospital Pediátrico
Coimbra
3000-602
Portugal
+351 239 488 700
frodrigues@chc.min-saude.pt

Type

Scientific

Additional contact

Prof Adam Finn

ORCID ID

http://orcid.org/0000-0003-1756-5668

Contact details

Level 6
BRI Education Centre
Bristol
BS2 8AE
United Kingdom
0117 342 0172
adam.finn@bristol.ac.uk

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

1.3

Study information

Scientific title

Case control study to evaluate the effectiveness of the 4CMenB vaccine for protection against invasive meningococcal disease caused by group B Neisseria meningitidis in Portugal

Acronym

PT-BEST

Study hypothesis

That rates of full immunisation per licensed schedule for age with Bexsero will be significantly higher among children presenting with culture and/or PCR-proven meningococcus group B invasive disease will be significantly lower than among age and gender-matched controls presenting at the same hospitals at around the same time with conditions unrelated to meningococcal infection.

Ethics approval

Approved 14/05/2018, Ethics Committee from Centro Hospitalar e Universitário de Coimbra (Centro Hospitalar Universitário de Coimbra, Serviço de Doenças Infecciosas, Praceta Mota Pinto, 3000-075 Coimbra, Portugal; +351 239 400 402; jscunha@fmed.uc.pt), ref: CHUC-099-17
National Data Protection authorisation number 306/ 2018

Study design

Multi-centre density case-control study

Primary study design

Observational

Secondary study design

Case crossover study

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

No participant information sheet available

Condition

Neisseria meningitidis

Intervention

All children and adolescents diagnosed with invasive meningococcal disease in Portugal between October 2014 and March 2019 inclusive will be eligible for inclusion. For each case, 2-4 age and location matched controls will be identified.

The study involves examination of medical records and extraction of anonymised information.

Intervention type

Biological/Vaccine

Phase

Phase IV

Drug names

4CMenB (Bexsero®)

Primary outcome measure

Effectiveness of the 4CMenB vaccine for protection against invasive meningococcal disease caused by group B Nm in Portugal (partially immunized children considered unvaccinated). Data are extracted from the medical records of cases and matched controls including immunisation history.

Secondary outcome measures

1. Effectiveness of the 4CMenB vaccine for protection against invasive meningococcal disease caused by group B Nm in Portugal when partially vaccinated children are excluded from analysis.
2. Effectiveness of one or more doses of 4CMenB vaccine for protection against invasive meningococcal disease caused by group B Nm in Portugal (i.e. partially vaccinated children included in analysis but considered to be vaccinated).
3. Effectiveness of the 4CMenB vaccine, using the 3 approaches summarized above, for protection against all-cause invasive meningococcal disease in Portugal.
Standardised data are extracted from the medical records of cases and matched controls including immunisation history.

Overall trial start date

01/01/2017

Overall trial end date

01/06/2019

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

Case participant inclusion criteria:
1. Age > 2 months and 14 days and < 18 years
2. Meningococcal invasive disease confirmed by culture or PCR in a normally-sterile biological sample (blood, CSF, pleural fluid, joint fluid, other)
3. Resident in Portugal at time of presentation
4. Eligible to have received and responded to 4CMenB (age at least 2 months and 14 days, absence of vaccine contraindication)
5. Available information about vaccine status for 4CMenB, MenC and MenACWY from central immunisation records database.

Control participant inclusion criteria:
6. Born within specified time period of matched case participant. If case is less than < 2 years old, controls have to have been born +/- 14 days (minimum age of 2 months and 14 days); if cases are aged 2-5 years, controls have to have been born +/- 60 days, if cases are aged >= 5 years or more, controls have to have been born +/-90 days
7. Eligible to have received and responded to 4CMenB (aged at least ≥ 2 months and 14 days, absence of vaccine contraindication)
8. Living in the same district as the case
9. Same gender as the case
10. Presenting to the same hospital, within the same week of the case (up to 14 days before or after the day when the case was observed), with an illness that was clearly not invasive meningococcal disease (i.e. not meningitis, septicaemia or pyrexia of unknown origin)
11. Available information about vaccine status for 4CMenB, MenC and MenACWY from central immunisation records database

Vaccination status:
For the primary analysis, children who have received the appropriate number of vaccine doses for their age will be considered vaccinated – i.e. those aged 4 to 15 months who have had 2 or more vaccine doses with the second dose at least 14 days before presentation and those aged 16 months or more who have had either 2 or 3 doses before 1 year of age and one dose after 1 year of age (with the booster dose at least 14 days before presentation) or who have had at least 2 vaccine doses after the first birthday (with the second dose at least 14 days before presentation). All children who have received fewer than the appropriate number of doses as defined above will be considered unvaccinated. Children too young to have received two priming doses with the second at least 14 days before presentation (i.e. less than 4 months and 14 days old) will not be included in this analysis.

Participant type

Mixed

Age group

Child

Gender

Both

Target number of participants

At an estimated 30% vaccine coverage for 80% power at a 5% level of significance, we require a minimum of 36 cases and 72 controls. If the vaccine uptake in controls is 20% these number rise to 54 cases and 108 controls.

Participant exclusion criteria

1. Unknown vaccine status from centralised immunisation records database
2. Belonging to a risk group for meningococcal invasive disease: asplenia, immunodeficiency including but not restricted to complement deficiency or on treatment with Eculizumab
3. History of invasive meningococcal disease
4. Recent known or suspected contact with a case of meningococcal invasive disease

Recruitment start date

01/04/2018

Recruitment end date

01/09/2019

Locations

Countries of recruitment

Portugal

Trial participating centre

Hospital Pediátrico - Centro Hospitalar e Universitário de Coimbra
Av. Afonso Romão
Coimbra
3000-602
Portugal

Trial participating centre

Centro Materno Infantil do Norte
Largo da Maternidade de Júlio Dinis
Porto
4050-651
Portugal

Trial participating centre

Hospital S. Pedro - Centro Hospitalar Trás-os-Montes e Alto Douro
R. dos Lagoeiros 43
Vila Real
5000-508 
Portugal

Trial participating centre

Centro Hospitalar da Póvoa do Varzim/Vila do Conde
Largo da Misericórdia
Póvoa do Varzim
4490-421
Portugal

Trial participating centre

Centro Hospitalar de Vila Nova de Gaia
Rua Conceição Fernandes, s/n 
Vila Nova de Gaia
4434-502
Portugal

Trial participating centre

Centro Hospitalar Barreiro Montijo
Av. Movimento das Forças Armadas 79C
Barreiro
2830-003
Portugal

Trial participating centre

Centro Hospitalar de S. João
Alameda Prof. Hernâni Monteiro
Porto
4200-319 
Portugal

Trial participating centre

Hospital de Faro - Centro Hospitalar do Algarve
R. Leão Penedo
Faro
8000-386 
Portugal

Trial participating centre

Hospital de Aveiro - Centro Hospitalar do Baixo Vouga
 Avenida Doutor Artur Ravara
Aveiro
3810-193
Portugal

Trial participating centre

Hospital D. Estefânia - Centro Hospitalar Lisboa Central
R. Jacinta Marto
Lisboa
1169-045
Portugal

Trial participating centre

H. Santa Maria - Centro Hospitalar Lisboa Norte
Av. Prof. Egas Moniz
Lisboa
1649-035 
Portugal

Trial participating centre

Hospital Padre Américo - Centro Hospitalar Tâmega e Sousa
Avenida do Hospital Padre Américo 210
Penafiel
4564-007
Portugal

Trial participating centre

Centro Hospitalar da Cova da Beira
Quinta do Alvito
Covilhã
6200-251
Portugal

Trial participating centre

Hospital de Torres Novas - Centro Hospitalar do Médio Tejo
R. Xanana Gusmão, 45
Torres Novas
2350-754
Portugal

Trial participating centre

Hospital Beatriz Angelo
Av. Carlos Teixeira, 514
Loures
3 2674-514 
Portugal

Trial participating centre

Hospital Cuf Descobertas
R. Mário Botas
Lisboa
1998-018 
Portugal

Trial participating centre

Hospital CUF Porto
Estrada da Circunvalação, 14341
Porto
4100-180 
Portugal

Trial participating centre

Hospital de Braga
Sete Fontes - São Victor
Braga
4710-243
Portugal

Trial participating centre

Hospital de Cascais
Av. Brigadeiro Victor Novais Gonçalves
Cascais
2755-009 
Portugal

Trial participating centre

Hospital de S. Teotónio - Centro Hospitalar Tondela Viseu
Av. Rei Dom Duarte
Viseu
3504-509 
Portugal

Trial participating centre

Hospital de Santarém
Av. Bernardo Santareno, 3737B
Santarém
2005-177Hospital de Santo Espírito
Portugal

Trial participating centre

Hospital de Santo Espírito
Canada do Briado
Terceira
9700-049
Portugal

Trial participating centre

Hospital do Divino Espírito Santo
Av. D. Manuel I - Matriz 
Ponta Delgada
9500-370
Portugal

Trial participating centre

Hospital Espírito Santo
Largo do Sr. da Pobreza
Évora
7000-811
Portugal

Trial participating centre

Hospital Fernando da Fonseca
IC 19
Amadora
2720-276
Portugal

Trial participating centre

Hospital Garcia de Orta
Av. Torrado da Silva
Almada
2805-267
Portugal

Trial participating centre

Hospital S. Bernardo
R. Camilo Castelo Branco 175
Setúbal
2910-549
Portugal

Trial participating centre

Hospital Senhora da Oliveira
R. dos Cutileiros 114, Creixomil
Guimarães
4835-044
Portugal

Trial participating centre

ULS Baixo Alentejo - Hospital de Beja
R. Dr. Antonio Fernando Covas Lima
Beja
7801-849
Portugal

Trial participating centre

Unidade Local de Saúde Alto Minho - Hospital de S. Luzia
Estr. de Santa Luzia 50
Viana do Castelo
4901-858 
Portugal

Trial participating centre

Hospital de S. André - Centro Hospitalar de Leiria
R. de Santo André
Leiria
2410-197
Portugal

Trial participating centre

Hospital Privado Algarve
Urbanização Casal de Gambelas
Faro
8005-226
Portugal

Trial participating centre

Hospital Nélio Mendonça
Av. Luís de Camões 6180
Funchal
9000-177
Portugal

Sponsor information

Organisation

Sociedade Portuguese de Pediatria

Sponsor details

R. Gaivotas em Terra 6C Piso 0
Lisboa
1990-601
Portugal
+351 21 757 4680
secretariado@spp.pt

Sponsor type

Other

Website

http://www.spp.pt

Funders

Funder type

Other

Funder name

Investigator initiated and funded.

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

It is anticipated that this research will lead to publications in one or more journals covering the areas of paediatric infectious disease or vaccine research. Initial results will be presented at The European Meningococcal Disease Society 27/05/2019.

IPD sharing statement:
The datasets generated during and/or analysed during the current study will be stored in a publically available repository
University of Bristol Research Data Repository
data.bris
https://www.bristol.ac.uk/staff/researchers/data/accessing-research-data/
Anonymised dataset used to calculate effectiveness (both primary and secondary endpoints) including age in months, date of presentation and immunisation history of cases and controls.
Data will become available when study is published and will be available indefinitely.
Data will be open access and users will be able to download and analyse it in whatever way they wish.
This study was a case-control study involving access to personally identifiable information only by managing clinical teams and no identifiers were provided to researchers running the study and undertaking the analysis.
It was not feasible nor deemed necessary by the ethical committee and data protection regulators to obtain consent from cases or controls.
There are no ethical or legal restrictions.

Intention to publish date

01/08/2019

Participant level data

Available on request

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

20/05/2019: Trial’s existence confirmed by Ethics Committee from Centro Hospitalar e Universitário de Coimbra.