<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01681979</url>
  </required_header>
  <id_info>
    <org_study_id>114593</org_study_id>
    <secondary_id>WEUSRTP4850</secondary_id>
    <secondary_id>EPI40638</secondary_id>
    <nct_id>NCT01681979</nct_id>
  </id_info>
  <brief_title>WEUSRTP4850: Phase II: ICS/LABA Use in Pregnancy and Outcomes</brief_title>
  <official_title>WEUSRTP4850: Phase II: Asthma Treatment in Pregnancy and the Frequency of Adverse Pregnancy Outcomes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>GlaxoSmithKline</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>GlaxoSmithKline</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Asthma is reported to affect between 3-14% of pregnancies making asthma medicines one of the&#xD;
      most commonly used classes of medicines during pregnancy. Maternal asthma and in particular&#xD;
      poorly controlled asthma has been found to be associated with a number of adverse perinatal&#xD;
      outcomes including preterm delivery, low birth weight and pre-eclampsia. At present little is&#xD;
      known about the safety in humans of many anti-asthma medicines when used during pregnancy. As&#xD;
      a result all inhaled corticosteroids, with the exception of budesonide which is category B,&#xD;
      have an FDA pregnancy category C, indicative of the fact there are no adequate and well&#xD;
      controlled studies in humans.&#xD;
&#xD;
      Fluticasone propionate is an inhaled corticosteroid used for the treatment of asthma, often&#xD;
      in combination with the long-acting β-agonist salmeterol. Owing to small numbers of pregnancy&#xD;
      exposures in the past, little is known about the safety of fluticasone propionate when used&#xD;
      during pregnancy. A recent feasibility study, however, has shown that there are sufficient&#xD;
      numbers of first trimester exposed pregnancies on the General Practice Research Database&#xD;
      (GPRD) to allow the overall risk of major congenital malformations (MCMs) to be evaluated.&#xD;
      This study also demonstrated that using data from the GPRD it is possible to determine an&#xD;
      individual's exposure to anti-asthma medicines during pregnancy and to classify her treatment&#xD;
      in terms of the British Thoracic Society treatment steps based on linked prescription and&#xD;
      primary care data.&#xD;
&#xD;
      The aims of this study are to 1) evaluate the safety profile of fluticasone propionate (FP)&#xD;
      compared with exposure to all other inhaled corticosteroids with all major congenital&#xD;
      malformations combined as the primary endpoint, whilst taking into account potential&#xD;
      confounders and exposure to other anti-asthma medicine; and 2) test the null hypothesis that&#xD;
      exposure to fluticasone propionate during the first trimester of pregnancy is not associated&#xD;
      with increased overall risk of all major congenital malformations when compared to the risk&#xD;
      in those exposed to other inhaled corticosteroids during the first trimester of pregnancy.&#xD;
&#xD;
      The study will be a retrospective cohort study and will use data from the United Kingdom's&#xD;
      General Practice Research Database (GPRD). The GPRD contains longitudinal medical records&#xD;
      collected within UK primary care. All medical symptoms and diagnoses are recorded in the&#xD;
      database, including those relating to pregnancy, in the form of Read Codes. In addition to&#xD;
      coded data GPs have the option of recording un-coded comments ('free text'), such as more&#xD;
      detailed descriptions of diagnoses or treatments along with information provided to them via&#xD;
      hospital letters, referrals and discharge summaries.&#xD;
&#xD;
      As the recording of stillbirths, neonatal deaths and pre-term births on the GPRD has not been&#xD;
      verified, a verification exercise will be carried out. This will involve requesting and&#xD;
      reviewing free text comments for 100 stillbirths, 100 neonatal deaths and 100 pre-term&#xD;
      births. Free text comments will be requested if they are associated with a medical code&#xD;
      related to pregnancy, delivery, post natal visits, death, post mortem, hospital letters and&#xD;
      other forms of communication. If the free text is not found to be informative we will send&#xD;
      questionnaires to the woman's GP.&#xD;
&#xD;
      All outcomes will be identified and verified blinded to asthma treatment and severity levels.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>July 2012</start_date>
  <completion_date type="Actual">August 2013</completion_date>
  <primary_completion_date type="Actual">August 2013</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>All major congenital malformations (MCMs) combined</measure>
    <time_frame>11 years (January 1, 2000 to December 31, 2010)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <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.</measure>
    <time_frame>11 years (January 1, 2000 to December 31, 2010)</time_frame>
    <description>Spontaneous pregnancy losses will be defined as losses that occurred &gt; 24 wks gestation from the date of the first day of the last menstrual period (LMP) (identified based on the pregnancy algorithm). For pregnancy losses where the type of loss is unknown any free text comments associated with the code will be requested &amp; reviewed. Pre-term births will be defined as a live birth delivered at &lt;37 complete wks gestation from the date of the first day of the LMP (identified based on medical codes for a pre-term delivery in addition to gestational age &amp; first day of LMP). Stillbirths =&gt;24 wks.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">1</enrollment>
  <condition>Asthma</condition>
  <arm_group>
    <arm_group_label>Women with asthma during pregnancy</arm_group_label>
    <description>Women with asthma during pregnancy will be identified based on one of the following: 1) an asthma related medical code recorded anytime before the pregnancy start date and at least one prescription for an asthma medicine in the 6 months before the pregnancy start date or during pregnancy; 2) no asthma related medical code but at least 6 prescriptions for an asthma medicine in their record before the pregnancy start date, including one in the 6 months before the pregnancy start date or during pregnancy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fluticasone propionate (with and without concurrent salmeterol)</intervention_name>
    <description>Fluticasone propionate is an inhaled corticosteroid used for the treatment of asthma, often in combination with the long-acting β-agonist salmeterol. For the primary endpoint, exposure status will be determined based on the individual receiving a prescription for the drug of interest (fluticasone propionate or another inhaled corticosteroid) in the 2 weeks immediately before the LMP date or during the first trimester of pregnancy.&#xD;
Sensitivity analysis will be carried out categorising exposure based on mapping the duration of prescriptions based on the number of inhalers, number of puffs within an inhaler and the prescribed daily dose.</description>
    <arm_group_label>Women with asthma during pregnancy</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        The study population will consist of all eligible pregnancies identified from the source&#xD;
        population where the female is considered to have asthma. The source population will be all&#xD;
        pregnancies identified on the GPRD that started and ended between 1 January 2000 and 31&#xD;
        December 2010.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  female patients whose pregnancy was registered on the GPRD and started and ended&#xD;
             between 1 January 2000 and 31 December 2010&#xD;
&#xD;
          -  Patients are considered to have asthma based on diagnosis and prescription codes&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  patients not registered with a practice contributing up-to-standard data to the GPRD&#xD;
             for the 6 months before the start of pregnancy, throughout pregnancy and for the 3&#xD;
             months following the pregnancy end date.&#xD;
&#xD;
          -  patients not 11-50 years of age on the pregnancy start date&#xD;
&#xD;
          -  patients who experienced multiple birth (twins, triplets)&#xD;
&#xD;
          -  patients with a medical code for a diagnosis of chronic obstructive pulmonary disease&#xD;
             (COPD) or any other chronic respiratory condition (e.g. cystic fibrosis) recorded at&#xD;
             anytime before the pregnancy end date&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>11 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>GSK Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>GlaxoSmithKline</affiliation>
  </overall_official>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>September 6, 2012</study_first_submitted>
  <study_first_submitted_qc>September 6, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 10, 2012</study_first_posted>
  <last_update_submitted>September 29, 2014</last_update_submitted>
  <last_update_submitted_qc>September 29, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 1, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>fluticasone propionate</keyword>
  <keyword>asthma</keyword>
  <keyword>pregnancy</keyword>
  <keyword>major congenital malformations</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Asthma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fluticasone</mesh_term>
    <mesh_term>Xhance</mesh_term>
    <mesh_term>Salmeterol Xinafoate</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01681979
org study id: 114593
secondary id: WEUSRTP4850
secondary id: EPI40638
nct id: NCT01681979
lead sponsor: 
has dmc: No
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.
observational model: Cohort
time perspective: Retrospective
measure: All major congenital malformations (MCMs) combined
time frame: 11 years (January 1, 2000 to December 31, 2010)
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.
time frame: 11 years (January 1, 2000 to December 31, 2010)
description: Spontaneous pregnancy losses will be defined as losses that occurred > 24 wks gestation from the date of the first day of the last menstrual period (LMP) (identified based on the pregnancy algorithm). For pregnancy losses where the type of loss is unknown any free text comments associated with the code will be requested & reviewed. Pre-term births will be defined as a live birth delivered at <37 complete wks gestation from the date of the first day of the LMP (identified based on medical codes for a pre-term delivery in addition to gestational age & first day of LMP). Stillbirths =>24 wks.
arm group label: Women with asthma during pregnancy
description: Women with asthma during pregnancy will be identified based on one of the following: 1) an asthma related medical code recorded anytime before the pregnancy start date and at least one prescription for an asthma medicine in the 6 months before the pregnancy start date or during pregnancy; 2) no asthma related medical code but at least 6 prescriptions for an asthma medicine in their record before the pregnancy start date, including one in the 6 months before the pregnancy start date or during pregnancy.
intervention type: Drug
intervention name: Fluticasone propionate (with and without concurrent salmeterol)
description: Fluticasone propionate is an inhaled corticosteroid used for the treatment of asthma, often in combination with the long-acting β-agonist salmeterol. For the primary endpoint, exposure status will be determined based on the individual receiving a prescription for the drug of interest (fluticasone propionate or another inhaled corticosteroid) in the 2 weeks immediately before the LMP date or during the first trimester of pregnancy.
Sensitivity analysis will be carried out categorising exposure based on mapping the duration of prescriptions based on the number of inhalers, number of puffs within an inhaler and the prescribed daily dose.
arm group label: Women with asthma during pregnancy
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
minimum age: 11 Years
maximum age: 50 Years
healthy volunteers: No
last name: GSK Clinical Trials
role: Study Director
affiliation: GlaxoSmithKline
responsible party type: Sponsor
mesh term: Asthma
mesh term: Fluticasone
mesh term: Xhance
mesh term: Salmeterol Xinafoate