<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/NCT03818867</url>
  </required_header>
  <id_info>
    <org_study_id>17.004</org_study_id>
    <nct_id>NCT03818867</nct_id>
  </id_info>
  <brief_title>Emergency Cerclage in Twin Pregnancies at Imminent Risk of Preterm Birth: an Open-Label Randomised Controlled Trial</brief_title>
  <acronym>ENCIRCLE</acronym>
  <official_title>Study Title: Emergency Cerclage in Twin Pregnancies at Imminent Risk of Preterm Birth: an Open-Label Randomised Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>St George's, University of London</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>St George's, University of London</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Twin pregnancies are at an increased risk of early delivery. One of the reasons for this may&#xD;
      be due to a weakened neck of the womb (cervix). There are 2 main ways to manage a weakened&#xD;
      cervix in pregnancy. One option is to do nothing (conservative approach). The other is to&#xD;
      strengthen the cervix with a stitch (cerclage) to provide extra support. There is no good&#xD;
      quality convincing evidence to suggest which of these has better outcomes for mum and babies&#xD;
      in twin pregnancies. This trial aims to determine whether securing the weakened cervix with a&#xD;
      cerclage will help to prolong the pregnancy and prevent early delivery. Babies who are born&#xD;
      early experience multiple complications including lung, brain and learning difficulties.&#xD;
      Therefore, the study will also aim to determine whether prolonging the pregnancy by inserting&#xD;
      the cerclage reduces the number of babies affected by these problems. In order to carry out a&#xD;
      fair study we aim to perform what is known as a randomised controlled trial. We will include&#xD;
      in the trial two major groups: (1) women pregnant with twins, who present with a weakened&#xD;
      cervix and no signs of infection between 14 and 26 weeks of pregnancy. This will be diagnosed&#xD;
      on an internal examination or ultrasound scan, and (2) women pregnant with identical twins&#xD;
      complicated by twin-to-twin transfusion syndrome (TTTS) treated by Laser surgery between 16&#xD;
      and 26 weeks in whom a short cervix (&lt;15mm) is identified. TTTS is rare but potentially&#xD;
      devastating condition which occurs in about 10-15% of identical twin pregnancies. If left&#xD;
      untreated, 80-90% of these babies will die. Overall, best first-line treatment of TTTS is&#xD;
      laser surgery. Cervical length is a strong predictor of preterm delivery in these&#xD;
      pregnancies.&#xD;
&#xD;
      Participants will be allocated randomly into the intervention (cerclage) or control&#xD;
      (conservative) group. The procedure to insert the cerclage will be performed under an&#xD;
      anaesthetic to minimise discomfort and you will be admitted for 2-3 days following the&#xD;
      operation to ensure there are no complications or signs of labour. Women in both groups will&#xD;
      be followed up in the same manner until they deliver and the pregnancy outcomes will be&#xD;
      compared between the 2 groups to determine which management option is best.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study hypothesis is that the placement of an emergency cervical cerclage prolongs the&#xD;
      pregnancy in (1) twin pregnancies with a dilated internal cervical os between 14+0 and 26+0&#xD;
      weeks, and (2) in monochorionic twin pregnancies complicated by TTTS treated by Laser surgery&#xD;
      between 16+0 and 26+0 weeks' gestation in whom a short cervix (&lt;15mm) is identified.&#xD;
&#xD;
      Study Design: Randomised controlled trial&#xD;
&#xD;
      Study population:&#xD;
&#xD;
      2 groups&#xD;
&#xD;
        -  Twin pregnancies between 14 - 26 weeks' gestation presenting with an open cervix&#xD;
&#xD;
        -  Monochorionic twin pregnancies complicated by twin-to-twin transfusion syndrome (TTTS)&#xD;
           treated by Laser surgery between 16+0 and 26+0 weeks' gestation in whom a short cervix&#xD;
           (&lt;15mm) is identified&#xD;
&#xD;
      The primary outcome is time to delivery (from randomisation to birth). Secondary outcomes&#xD;
      include gestation at delivery, preterm birth before 28, 32 and 34 weeks' gestation,&#xD;
      birthweight, stillbirth, neonatal death, survival to discharge, days of admission to the&#xD;
      neonatal intensive care unit, composite outcome of stillbirth, neonatal death,&#xD;
      intraventricular haemorrhage, periventricular leukomalacia, respiratory distress syndrome,&#xD;
      bronchopulmonary dysplasia, retinopathy of prematurity, necrotising entercolitis, proven&#xD;
      neonatal sepsis, or the need for ventilation, days of maternal admission for preterm labour&#xD;
      and maternal morbidity.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">May 15, 2017</start_date>
  <completion_date type="Anticipated">December 2019</completion_date>
  <primary_completion_date type="Anticipated">July 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time to delivery (from randomisation to birth).</measure>
    <time_frame>2 weeks after expected date of birth</time_frame>
    <description>Time between randomisation and delivery in days</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Gestation at delivery</measure>
    <time_frame>2 weeks after expected date of birth</time_frame>
    <description>gestational age at delivery in weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Preterm birth before 28, 32 and 34 weeks' gestation</measure>
    <time_frame>2 weeks after expected date of birth</time_frame>
    <description>the proportion of women giving birth before 28, 32 and 34 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Birthweight</measure>
    <time_frame>42 days (28 days neonatal period+2 weeks postdates)</time_frame>
    <description>birth weight in grams</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stillbirth</measure>
    <time_frame>42 days (28 days neonatal period+2 weeks postdates)</time_frame>
    <description>death of the fetus (after 24 weeks) and before birth</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neonatal death</measure>
    <time_frame>42 days (28 days neonatal period+2 weeks postdates)</time_frame>
    <description>the death of a baby within the first 28 days of life</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Survival to discharge</measure>
    <time_frame>42 days (28 days neonatal period+2 weeks postdates)</time_frame>
    <description>the proportion of the babies surviving until discharge from the hospital after birth</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Days of admission to the neonatal intensive care unit</measure>
    <time_frame>42 days (28 days neonatal period+2 weeks postdates)</time_frame>
    <description>Number of days the baby was admitted in the neonatal intensive care unit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Composite outcome</measure>
    <time_frame>42 days (28 days neonatal period+2 weeks postdates)</time_frame>
    <description>An outcome which includes any of these outcomes (stillbirth, neonatal death, intraventricular haemorrhage, periventricular leukomalacia, respiratory distress syndrome, bronchopulmonary dysplasia, retinopathy of prematurity, necrotising entercolitis, proven neonatal sepsis, or the need for ventilation)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Days of maternal admission for preterm labour</measure>
    <time_frame>2 weeks after expected date of birth</time_frame>
    <description>Number of days the mother was admitted to the hospital because of preterm labour</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maternal morbidity (deﬁned as thromboembolic complications, chorioamnionitis, urinary tract infection treated with antibiotics, pneumonia, endometritis, eclampsia, HELLP syndrome, death, or any other significant morbidity)</measure>
    <time_frame>2 weeks after expected date of birth</time_frame>
    <description>complications to the mother related to preterm labour or the insertion of the stitch</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">31</enrollment>
  <condition>Preterm Birth</condition>
  <condition>Twin Pregnancy With Antenatal Problem</condition>
  <condition>Twin to Twin Transfusion Syndrome</condition>
  <arm_group>
    <arm_group_label>Cerclage arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pregnancies which had cervical cerclage inserted.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No-cerclage arm</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Pregnancies which did not have cervical cerclage inserted.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Insertion of cervical cerclage</intervention_name>
    <description>insertion of a stitch around the neck of the womb in order to provide extra support.</description>
    <arm_group_label>Cerclage arm</arm_group_label>
    <other_name>cervical stitch</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Twin pregnancies presenting with an open cervix between 14 and 26 weeks of gestation,&#xD;
             OR&#xD;
&#xD;
          -  Twin pregnancies complicated by TTTS treated by Laser surgery between 16+0 and 26+0&#xD;
             weeks' gestation in whom a short cervix (&lt;15mm) is identified.&#xD;
&#xD;
          -  Age &gt;18 years&#xD;
&#xD;
          -  Informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Cervical dilatation ≥5cm&#xD;
&#xD;
          -  Amniotic membranes prolapsed beyond external os into the vagina, unable to visualise&#xD;
             cervical tissue&#xD;
&#xD;
          -  Preterm premature rupture of the membranes (PPROM) at the time of diagnosis of dilated&#xD;
             cervix&#xD;
&#xD;
          -  Major fetal malformations unrelated to TTTS&#xD;
&#xD;
          -  Intrauterine death of one or both fetuses&#xD;
&#xD;
          -  Symptoms or signs of threatened imminent delivery, e.g. painful regular uterine&#xD;
             contractions, active vaginal bleeding, history of ruptured membranes&#xD;
&#xD;
          -  Suspected chorioamnionitis [based on maternal uterine tenderness, a temperature of&#xD;
             38°C or greater, significant leucocytosis (&gt;15,000 x 106/L) or elevated C-reactive&#xD;
             protein (&gt;15 mg/L), or maternal tachycardia].&#xD;
&#xD;
          -  Placenta praevia&#xD;
&#xD;
          -  Monochorionic monoamniotic twin pregnancies&#xD;
&#xD;
          -  Prophylactic cervical cerclage&#xD;
&#xD;
          -  Women who are not able to give valid consent, e.g. unconscious or severely ill&#xD;
&#xD;
          -  Mental health disorder which impairs the ability to give fully informed consent&#xD;
&#xD;
          -  Women under the age of 18 years&#xD;
&#xD;
          -  Higher order multiple pregnancies&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Asma Khalil</last_name>
    <role>Principal Investigator</role>
    <affiliation>St George's NHS Healthcare Trust</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Asma Khalil</last_name>
    <phone>7917400164</phone>
    <email>akhalil@sgul.ac.uk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Rosemary Townsend</last_name>
    <email>rosemary.townsend1@nhs.net</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>St George's Hospital</name>
      <address>
        <city>London</city>
        <zip>SW17 0QT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Asma Khalil</last_name>
      <phone>7917400164</phone>
      <email>akhalil@sgul.ac.uk</email>
    </contact>
    <contact_backup>
      <last_name>Rosemary Townsend</last_name>
      <email>rosemary.townsend1@nhs.net</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 23, 2019</study_first_submitted>
  <study_first_submitted_qc>January 23, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 28, 2019</study_first_posted>
  <last_update_submitted>January 23, 2019</last_update_submitted>
  <last_update_submitted_qc>January 23, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 28, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>cervical cerclage</keyword>
  <keyword>Preterm Birth</keyword>
  <keyword>Twin pregnancy</keyword>
  <keyword>Twin to Twin Transfusion Syndrome</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Premature Birth</mesh_term>
    <mesh_term>Fetofetal Transfusion</mesh_term>
    <mesh_term>Emergencies</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>May 15, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/67/NCT03818867/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03818867
org study id: 17.004
nct id: NCT03818867
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Twin pregnancies are at an increased risk of early delivery. One of the reasons for this may
      be due to a weakened neck of the womb (cervix). There are 2 main ways to manage a weakened
      cervix in pregnancy. One option is to do nothing (conservative approach). The other is to
      strengthen the cervix with a stitch (cerclage) to provide extra support. There is no good
      quality convincing evidence to suggest which of these has better outcomes for mum and babies
      in twin pregnancies. This trial aims to determine whether securing the weakened cervix with a
      cerclage will help to prolong the pregnancy and prevent early delivery. Babies who are born
      early experience multiple complications including lung, brain and learning difficulties.
      Therefore, the study will also aim to determine whether prolonging the pregnancy by inserting
      the cerclage reduces the number of babies affected by these problems. In order to carry out a
      fair study we aim to perform what is known as a randomised controlled trial. We will include
      in the trial two major groups: (1) women pregnant with twins, who present with a weakened
      cervix and no signs of infection between 14 and 26 weeks of pregnancy. This will be diagnosed
      on an internal examination or ultrasound scan, and (2) women pregnant with identical twins
      complicated by twin-to-twin transfusion syndrome (TTTS) treated by Laser surgery between 16
      and 26 weeks in whom a short cervix (<15mm) is identified. TTTS is rare but potentially
      devastating condition which occurs in about 10-15% of identical twin pregnancies. If left
      untreated, 80-90% of these babies will die. Overall, best first-line treatment of TTTS is
      laser surgery. Cervical length is a strong predictor of preterm delivery in these
      pregnancies.

      Participants will be allocated randomly into the intervention (cerclage) or control
      (conservative) group. The procedure to insert the cerclage will be performed under an
      anaesthetic to minimise discomfort and you will be admitted for 2-3 days following the
      operation to ensure there are no complications or signs of labour. Women in both groups will
      be followed up in the same manner until they deliver and the pregnancy outcomes will be
      compared between the 2 groups to determine which management option is best.
The study hypothesis is that the placement of an emergency cervical cerclage prolongs the
      pregnancy in (1) twin pregnancies with a dilated internal cervical os between 14+0 and 26+0
      weeks, and (2) in monochorionic twin pregnancies complicated by TTTS treated by Laser surgery
      between 16+0 and 26+0 weeks' gestation in whom a short cervix (<15mm) is identified.

      Study Design: Randomised controlled trial

      Study population:

      2 groups

        -  Twin pregnancies between 14 - 26 weeks' gestation presenting with an open cervix

        -  Monochorionic twin pregnancies complicated by twin-to-twin transfusion syndrome (TTTS)
           treated by Laser surgery between 16+0 and 26+0 weeks' gestation in whom a short cervix
           (<15mm) is identified

      The primary outcome is time to delivery (from randomisation to birth). Secondary outcomes
      include gestation at delivery, preterm birth before 28, 32 and 34 weeks' gestation,
      birthweight, stillbirth, neonatal death, survival to discharge, days of admission to the
      neonatal intensive care unit, composite outcome of stillbirth, neonatal death,
      intraventricular haemorrhage, periventricular leukomalacia, respiratory distress syndrome,
      bronchopulmonary dysplasia, retinopathy of prematurity, necrotising entercolitis, proven
      neonatal sepsis, or the need for ventilation, days of maternal admission for preterm labour
      and maternal morbidity.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Time to delivery (from randomisation to birth).
time frame: 2 weeks after expected date of birth
description: Time between randomisation and delivery in days
measure: Gestation at delivery
time frame: 2 weeks after expected date of birth
description: gestational age at delivery in weeks
measure: Preterm birth before 28, 32 and 34 weeks' gestation
time frame: 2 weeks after expected date of birth
description: the proportion of women giving birth before 28, 32 and 34 weeks
measure: Birthweight
time frame: 42 days (28 days neonatal period+2 weeks postdates)
description: birth weight in grams
measure: Stillbirth
time frame: 42 days (28 days neonatal period+2 weeks postdates)
description: death of the fetus (after 24 weeks) and before birth
measure: Neonatal death
time frame: 42 days (28 days neonatal period+2 weeks postdates)
description: the death of a baby within the first 28 days of life
measure: Survival to discharge
time frame: 42 days (28 days neonatal period+2 weeks postdates)
description: the proportion of the babies surviving until discharge from the hospital after birth
measure: Days of admission to the neonatal intensive care unit
time frame: 42 days (28 days neonatal period+2 weeks postdates)
description: Number of days the baby was admitted in the neonatal intensive care unit
measure: Composite outcome
time frame: 42 days (28 days neonatal period+2 weeks postdates)
description: An outcome which includes any of these outcomes (stillbirth, neonatal death, intraventricular haemorrhage, periventricular leukomalacia, respiratory distress syndrome, bronchopulmonary dysplasia, retinopathy of prematurity, necrotising entercolitis, proven neonatal sepsis, or the need for ventilation)
measure: Days of maternal admission for preterm labour
time frame: 2 weeks after expected date of birth
description: Number of days the mother was admitted to the hospital because of preterm labour
measure: Maternal morbidity (deﬁned as thromboembolic complications, chorioamnionitis, urinary tract infection treated with antibiotics, pneumonia, endometritis, eclampsia, HELLP syndrome, death, or any other significant morbidity)
time frame: 2 weeks after expected date of birth
description: complications to the mother related to preterm labour or the insertion of the stitch
arm group label: Cerclage arm
arm group type: Experimental
description: Pregnancies which had cervical cerclage inserted.
arm group label: No-cerclage arm
arm group type: No Intervention
description: Pregnancies which did not have cervical cerclage inserted.
intervention type: Procedure
intervention name: Insertion of cervical cerclage
description: insertion of a stitch around the neck of the womb in order to provide extra support.
arm group label: Cerclage arm
other name: cervical stitch
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Asma Khalil
role: Principal Investigator
affiliation: St George's NHS Healthcare Trust
last name: Asma Khalil
phone: 7917400164
email: akhalil@sgul.ac.uk
last name: Rosemary Townsend
email: rosemary.townsend1@nhs.net
facility: 
status: Recruiting
contact: 
contact backup: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Premature Birth
mesh term: Fetofetal Transfusion
mesh term: Emergencies
provided document: 