Status: Finalised
First registered on:
24/02/2014
Last updated on:
21/03/2019
1. Study identification
EU PAS Register NumberEUPAS5899
Official titleRisk of Febrile Convulsions after a Second Immunization against Measles, Mumps and Rubella with MMRV as compared to MMR or MMR+V.
Study title acronymMMRV 2nd dose
Study typeObservational study
Brief description of the studyThe German Standing Vaccination Committee (STIKO) recommends vaccination against measles, mumps, rubella (MMR), and varicella (V) in all children at 11 to 14 months of age (1st dose) and revaccination at 15 to 23 months of age (2nd dose). In July 2006, the combined measles-mumps-rubella-varicella (MMRV) vaccine Priorix-Tetra® (GlaxoSmithKline) was licensed in Germany, which made simultaneous vaccination against all four infectious diseases possible. After licensure of the MMRV vaccine, studies on the safety of the vaccine have suggested an elevated risk for febrile convulsions (FC) in children vaccinated with a 1st dose of MMRV as compared to children vaccinated with separately administered MMR and V vaccines. Concerning the risk of FC after the 2nd dose of MMRV as compared with a 2nd dose of MMR or MMR+V, data was generally limited and no information was available for Germany, where the 2nd dose is recommended for relatively young children as compared to e.g. the US (recommendation for 2nd dose at the age 4 to 6 years). A retrospective matched cohort study was performed on the basis of statutory health insurance claims data from 2004 to 2008. For the determination of the risk of febrile seizures after administration of the 2nd dose of vaccination against measles, mumps and rubella (two doses are recommended at age 11-14 and 15-23 months in Germany), a total of 159,013 children were included in the study, of whom 50,350 (32%) had received the MMRV vaccine. Due to very low incidences of FC in the risk intervals under investigation, the power of the analyses was insufficient to draw reliable conclusions from the generated results and to exclude a risk of FC. Further analyses based on a larger sample size are planned.
Was this study requested by a regulator?Yes: Germany
Is the study required by a Risk Management Plan (RMP)?
Not applicable
Regulatory procedure number (RMP Category 1 and 2 studies only)
Other study registration identification numbers and URLs as applicable
2. Research centres and Investigator details
Coordinating study entity
Centre to which the investigator belongsBIPS GmbH
Department/Research groupClinical Epidemiology
Organisation/affiliationLeibniz Inst. for Prevention Research and Epidem.
Details of (Primary) lead investigator
Title Dr
Last name Schink
First name Tania
Is this study being carried out with the collaboration of a research network?
No
Other centres where this study is being conducted
Not applicable (single centre)
Countries in which this study is being conducted
National study
Germany
3. Study timelines: initial administrative steps, progress reports and final report
PlannedActual
Date when funding contract was signed26/03/201303/04/2013
Start date of data collection01/01/200401/01/2004
Start date of data analysis01/04/201301/04/2013
Date of interim report, if expected
Date of final study report31/07/201329/07/2013
4. Sources of funding
Please provide estimates of the percentage of funding by source for this study
Names(s)Approximate % funding
Pharmaceutical companiesGlaxoSmithKline Biologicals SA100
Charities
Government body
Research councils
EU funding scheme
5. Contact details for enquiries
Scientific Enquiries
Title Dr
Last name Schink
First name Tania
Address line 1Achterstraße 30
Address line 2
Address line 3
CityBremen
Postcode28359
CountryGermany
Phone number (incl. country code)49-421-21856860
Alternative phone number
Fax number (incl. country code)
Public Enquiries
Title Dr
Last name Gerds
First name Heike
Address line 1Achterstraße 30
Address line 2
Address line 3
CityBremen
Postcode28359
CountryGermany
Phone number (incl. country code)49-421-21856860
Alternative phone number
Fax number (incl. country code)
6. Study drug(s) information
Substance class (ATC Code)J07BD54 (measles, combinations with mumps, rubella and varicella, live attenuated)
Product NamePriorix-Tetra®
CountryGermany
Substance INN(s)MEASLES, MUMPS, RUBELLA AND VARICELLA VACCINE (LIVE)
7. Medical conditions to be studied
Medical condition(s)Yes
Febrile convulsion
8. Population under study
Age
Infants and toddlers (28 days - 23 months)
Children (2 - 11 years)
Sex
Male
Female
9. Number of subjects
Estimated total number of subjects159013
Additional information
82656 (29%) children received the MMRV vaccine.
10. Source of data
Is this study being carried out with an established data source?Yes
Data sources registered with ENCePP
Sources of data
Administrative database, e.g. claims database
11. Scope of the study
What is the scope of the study?
Risk assessment
Primary scope : Risk assessment
12. Main objective(s)
What is the main objective of the study?
The objective of this study was to estimate the risk of febrile convulsions after a first dose vaccination with Priorix-Tetra® in comparison to first dose vaccination with MMR or MMR+V in the pre-specified risk intervals: 0-4 days after immunization, 5-12 days after immunization (main risk interval), 13-30 days after immunization, and the entire risk period, that is 0-30 days after immunization.
Are there primary outcomes?Yes
The primary outcome of this study was the occurrence of febrile convulsions (FC) defined as hospitalization with a diagnosis of FC without any alternative plausible cause of FC, e.g. an infection or neurological condition, coded as main discharge diagnosis.
Are there secondary outcomes?Yes
The secondary outcome was defined as closely as possible to the outcome-criteria specified by the previous study by Jacobsen et al. That is, only hospitalizations for FC with a neurological condition coded as main discharge diagnosis were excluded.
13. Study design
What is the design of the study?
Cohort study
14. Follow-up of patients
Will patients be followed up?Not applicable/no follow-up
15. Data analysis plan
Please provide a brief summary of the analysis method
A retrospective matched cohort study was performed to provide risk estimates of FC after a 2nd dose of MMRV compared to MMR and MMR+V (index vaccines) in pre-defined risk intervals (RI). Insurants born from 01/01/2004 through 31/12/2008 who received a 2nd vaccination with one of the index vaccines were included in the cohort.
Cumulative incidences were calculated. . Relative risks and risk differences for the comparison of exposure groups were calculated with 95% CIs.
All children with a 2nd immunization with MMRV were matched 1:1 to children with a 2nd immunization with MMR or MMR+V by statutory health insurance, sex, age in months (± 1 month) and month of cohort entry (± 1 month).
Multivariable analyses were performed, adjusted for FC history, hospitalization for an infectious disease, administration of other vaccines, type of 1st dose vaccine, time between 1st and 2nd dose to estimate ORs with 95% CIs using a separate binary logistic regression model for each RI.
16. ENCePP seal
Are you requesting the ENCePP seal for this study?
No
17. Full protocol
Not submitted
18. Study Results
Please list the 5 most relevant publications using data from your study
ReferenceLink to web-publication
None
19. Other relevant documents
Conflict(s) of interest of
investigator(s)Not submitted
Composition of Steering Group and
ObserversNot submitted
Other documentsNot
submitted
Signed Code of
Conduct Checklist
Not submitted
Signed Code of Conduct Declaration
Not submitted
Signed Checklist for Study
Protocols
Not submitted
