1. Study identification
EU PAS Register NumberEUPAS2628
Official titleAsthma treatment in pregnancy and the frequency of adverse pregnancy outcomes (WEUSRTP4850)
Study title acronym
Study typeObservational study
Brief description of the studyFluticasone propionate (FP) is an inhaled corticosteroid (ICS) used for the treatment of asthma, often in combination with the long-acting β-agonist salmeterol. Owing to small numbers of pregnancy exposures in the past, little is known about the safety of FP when used during pregnancy. Now, however, there are sufficient 1st trimester exposed pregnancies on the General Practice Research Database to allow the overall risk of major congenital malformations (MCMs) following exposure to FP to be evaluated.
This study aims to evaluate the safety profile of FP compared with exposure to all other ICS with all MCMs combined as the primary endpoint whilst taking into account potential confounders and exposure to other asthma medicines. Analyses will be carried out separately for FP alone and FP in combination. If appropriate the two groups will be combined.
In order to give an overall picture of the risks of adverse pregnancy outcomes associated with asthma in general and different levels of asthma control, irrespective of the products used for treatment, this study will also evaluate -
1. The risk of MCMs in pregnancies to women with ‘considerable to severe’ and ‘moderate’ asthma activity during the 1st trimester of pregnancy compared with those with ‘mild’ asthma activity during the 1st trimester.
2. The prevalence of specific MCMs identified within the entire asthma population.
3. The risk of a spontaneous pregnancy loss to women with ‘considerable to severe’ and ‘moderate’ asthma activity during the 1st trimester of pregnancy compared with those with ‘mild’ asthma activity during the 1st trimester.
4. The risk of a pre-term delivery to women with ‘considerable to severe’ and ‘moderate’ asthma activity in the 3rd trimester of pregnancy compared with those with ‘mild’ asthma activity in the 3rd pregnancy trimester.
5. The analyses carried out for pre-term delivery will also be carried out to evaluate the risk of stillbirths and neonatal death.
Was this study requested by a regulator?No
Is the study required by a Risk Management Plan (RMP)?
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
Department/Research groupPharmacy & Pharmacology
Organisation/affiliationUniversity of Bath
Details of (Primary) lead investigator
Title Professor
Last name de Vries
First name Corinne
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
United Kingdom
3. Study timelines: initial administrative steps, progress reports and final report
PlannedActual
Date when funding contract was signed01/06/201201/06/2012
Start date of data collection23/07/201201/08/2012
Start date of data analysis
Date of interim report, if expected
Date of final study report28/02/201331/07/2013
4. Sources of funding
Please provide estimates of the percentage of funding by source for this study
Names(s)Approximate % funding
Pharmaceutical companiesGlaxoSmithKline100
Charities
Government body
Research councils
EU funding scheme
5. Contact details for enquiries
Scientific Enquiries
Title Dr
Last name Charlton
First name Rachel
Address line 1Dept. of Pharmacy & Pharmacology
Address line 2University of Bath
Address line 3Claverton Down
CityBath
PostcodeBA2 7AY
CountryUnited Kingdom
Phone number (incl. country code)44-1225-383672
Alternative phone number
Fax number (incl. country code)44-1225-386114
Public Enquiries
Title Dr
Last name Charlton
First name Rachel
Address line 1Dept. of Pharmacy & Pharmacology
Address line 2University of Bath
Address line 3Claverton Down
CityBath
PostcodeBA2 7AY
CountryUnited Kingdom
Phone number (incl. country code)44-1225-383672
Alternative phone number
Fax number (incl. country code)44-1225-386114
6. Study drug(s) information
Substance class (ATC Code)R03 (DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES)
7. Medical conditions to be studied
Medical condition(s)Yes
Asthma
8. Population under study
Age
Preterm newborns
Term newborns (0-27 days)
Infants and toddlers (28 days - 23 months)
Children (2 - 11 years)
Adolescents (12 - 17 years)
Adults (18 - 44 years)
Adults (45 - 64 years)
Sex
Female
Other population
Pregnant women
9. Number of subjects
Estimated total number of subjects30000
Additional information
Of the 30,000 about 1,200 first trimester exposures to fluticasone propionate and 3,600 first trimester exposures to other inhaled corticosteroids (ICS) are expected.
10. Source of data
Is this study being carried out with an established data source?Yes
Data sources registered with ENCePP
Sources of data
Routine primary care electronic patient registry
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?
To evaluate the safety profile of fluticasone propionate compared with exposure to all other inhaled corticosteroids, with all major congenital malformations combined as the primary endpoint, whilst taking into account potential confounders and exposure to other asthma medicines. This will be carried out separately for FP alone and in combination. If appropriate the 2 groups will be combined.
Are there primary outcomes?Yes
The primary outcome of interest will be all major congenital malformations (MCMs) combined. MCMs will be defined according to the EUROCAT (European network of population-based registers for the epidemiological surveillance of congenital anomalies) classification scheme. MCMs will exclude all chromosomal defects and congenital malformations known to be of a genetic origin.
Are there secondary outcomes?Yes
1. Spontaneous pregnancy losses
2. Pre-term births
3. Stillbirths at >24 weeks gestation
4. Neonatal deaths occurring in the first 4 weeks of life
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
The absolute risk of a pregnancy outcome with a major congenital malformation (MCM) will be calculated for the fluticasone propionate exposure groups, other inhaled corticosteroid (ICS) exposure group and the entire asthma cohort stratified by asthma activity level.
The relative risk of an MCM following first trimester exposure to fluticasone propionate compared to all other ICS will be calculated stratified by asthma activity level during the 1st trimester.
The prevalence of different types of MCMs identified in the fluticasone propionate exposure groups, other ICS exposure group and the entire asthma cohort will be calculated.
The risk of a spontaneous pregnancy loss, a pre-term delivery and a stillbirth will be calculated separately for the entire asthma cohort stratified by asthma activity level. Comparisons will be made between women classed as having ‘considerable to severe’ asthma activity and ‘moderate’ asthma activity to those with ‘mild’ asthma activity.