Clinical trial NCT01681979: WEUSRTP4850: Phase II: ICS/LABA Use in Pregnancy and Outcomes
Official title: WEUSRTP4850: Phase II: Asthma Treatment in Pregnancy and the Frequency of Adverse Pregnancy Outcomes
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Asthma
Keywords: fluticasone propionate
asthma
pregnancy
major congenital malformations
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2012-09-10
Enrollment: 1
Sex: FEMALE
Minimum age (years): 11
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population will consist of all eligible pregnancies identified from the source population where the female is considered to have asthma. The source population will be all pregnancies identified on the GPRD that started and ended between 1 January 2000 and 31 December 2010.

Brief 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.


Eligibility criteria: Inclusion Criteria:

* female patients whose pregnancy was registered on the GPRD and started and ended between 1 January 2000 and 31 December 2010
* Patients are considered to have asthma based on diagnosis and prescription codes

Exclusion Criteria:

* patients not registered with a practice contributing up-to-standard data to the GPRD for the 6 months before the start of pregnancy, throughout pregnancy and for the 3 months following the pregnancy end date.
* patients not 11-50 years of age on the pregnancy start date
* patients who experienced multiple birth (twins, triplets)
* patients with a medical code for a diagnosis of chronic obstructive pulmonary disease (COPD) or any other chronic respiratory condition (e.g. cystic fibrosis) recorded at anytime before the pregnancy end date

Primary outcomes:
measure: All major congenital malformations (MCMs) combined
timeFrame: 11 years (January 1, 2000 to December 31, 2010)
Secondary outcomes:
measure: Secondary outcomes associated with measures of asthma control, not drug exposures of interest including Spontaneous pregnancy losses, pre-term births, and Stillbirths and neonatal deaths.
timeFrame: 11 years (January 1, 2000 to December 31, 2010)
Other outcomes:
Locations:
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: