WEUSRTP4850: Phase II: ICS/LABA Use in Pregnancy and Outcomes
Status:
Completed
Trial end date:
2013-08-01
Target enrollment:
Participant gender:
Summary
Asthma is reported to affect between 3-14% of pregnancies making asthma medicines one of the
most commonly used classes of medicines during pregnancy. Maternal asthma and in particular
poorly controlled asthma has been found to be associated with a number of adverse perinatal
outcomes including preterm delivery, low birth weight and pre-eclampsia. At present little is
known about the safety in humans of many anti-asthma medicines when used during pregnancy. As
a result all inhaled corticosteroids, with the exception of budesonide which is category B,
have an FDA pregnancy category C, indicative of the fact there are no adequate and well
controlled studies in humans.
Fluticasone propionate is an inhaled corticosteroid 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 fluticasone propionate when used
during pregnancy. A recent feasibility study, however, has shown that there are sufficient
numbers of first trimester exposed pregnancies on the General Practice Research Database
(GPRD) to allow the overall risk of major congenital malformations (MCMs) to be evaluated.
This study also demonstrated that using data from the GPRD it is possible to determine an
individual's exposure to anti-asthma medicines during pregnancy and to classify her treatment
in terms of the British Thoracic Society treatment steps based on linked prescription and
primary care data.
The aims of this study are to 1) evaluate the safety profile of fluticasone propionate (FP)
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 anti-asthma medicine; and 2) test the null hypothesis that
exposure to fluticasone propionate during the first trimester of pregnancy is not associated
with increased overall risk of all major congenital malformations when compared to the risk
in those exposed to other inhaled corticosteroids during the first trimester of pregnancy.
The study will be a retrospective cohort study and will use data from the United Kingdom's
General Practice Research Database (GPRD). The GPRD contains longitudinal medical records
collected within UK primary care. All medical symptoms and diagnoses are recorded in the
database, including those relating to pregnancy, in the form of Read Codes. In addition to
coded data GPs have the option of recording un-coded comments ('free text'), such as more
detailed descriptions of diagnoses or treatments along with information provided to them via
hospital letters, referrals and discharge summaries.
As the recording of stillbirths, neonatal deaths and pre-term births on the GPRD has not been
verified, a verification exercise will be carried out. This will involve requesting and
reviewing free text comments for 100 stillbirths, 100 neonatal deaths and 100 pre-term
births. Free text comments will be requested if they are associated with a medical code
related to pregnancy, delivery, post natal visits, death, post mortem, hospital letters and
other forms of communication. If the free text is not found to be informative we will send
questionnaires to the woman's GP.
All outcomes will be identified and verified blinded to asthma treatment and severity levels.