Emergency Cerclage in Twin Pregnancies at Imminent Risk of Preterm Birth: an Open-Label Randomised Controlled Trial (ENCIRCLE)

January 23, 2019 updated by: St George's, University of London

Study Title: Emergency Cerclage in Twin Pregnancies at Imminent Risk of Preterm Birth: an Open-Label Randomised Controlled Trial

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Anticipated)

31

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Twin pregnancies presenting with an open cervix between 14 and 26 weeks of gestation, OR
  • 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.
  • Age >18 years
  • Informed consent

Exclusion Criteria:

  • Cervical dilatation ≥5cm
  • Amniotic membranes prolapsed beyond external os into the vagina, unable to visualise cervical tissue
  • Preterm premature rupture of the membranes (PPROM) at the time of diagnosis of dilated cervix
  • Major fetal malformations unrelated to TTTS
  • Intrauterine death of one or both fetuses
  • Symptoms or signs of threatened imminent delivery, e.g. painful regular uterine contractions, active vaginal bleeding, history of ruptured membranes
  • Suspected chorioamnionitis [based on maternal uterine tenderness, a temperature of 38°C or greater, significant leucocytosis (>15,000 x 106/L) or elevated C-reactive protein (>15 mg/L), or maternal tachycardia].
  • Placenta praevia
  • Monochorionic monoamniotic twin pregnancies
  • Prophylactic cervical cerclage
  • Women who are not able to give valid consent, e.g. unconscious or severely ill
  • Mental health disorder which impairs the ability to give fully informed consent
  • Women under the age of 18 years
  • Higher order multiple pregnancies

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cerclage arm
Pregnancies which had cervical cerclage inserted.
Procedure: Insertion of cervical cerclage
insertion of a stitch around the neck of the womb in order to provide extra support.
Other Names:
  • cervical stitch
No Intervention: No-cerclage arm
Pregnancies which did not have cervical cerclage inserted.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to delivery (from randomisation to birth).
Time Frame: 2 weeks after expected date of birth
Time between randomisation and delivery in days
2 weeks after expected date of birth

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Gestation at delivery
Time Frame: 2 weeks after expected date of birth
gestational age at delivery in weeks
2 weeks after expected date of birth
Preterm birth before 28, 32 and 34 weeks' gestation
Time Frame: 2 weeks after expected date of birth
the proportion of women giving birth before 28, 32 and 34 weeks
2 weeks after expected date of birth
Birthweight
Time Frame: 42 days (28 days neonatal period+2 weeks postdates)
birth weight in grams
42 days (28 days neonatal period+2 weeks postdates)
Stillbirth
Time Frame: 42 days (28 days neonatal period+2 weeks postdates)
death of the fetus (after 24 weeks) and before birth
42 days (28 days neonatal period+2 weeks postdates)
Neonatal death
Time Frame: 42 days (28 days neonatal period+2 weeks postdates)
the death of a baby within the first 28 days of life
42 days (28 days neonatal period+2 weeks postdates)
Survival to discharge
Time Frame: 42 days (28 days neonatal period+2 weeks postdates)
the proportion of the babies surviving until discharge from the hospital after birth
42 days (28 days neonatal period+2 weeks postdates)
Days of admission to the neonatal intensive care unit
Time Frame: 42 days (28 days neonatal period+2 weeks postdates)
Number of days the baby was admitted in the neonatal intensive care unit
42 days (28 days neonatal period+2 weeks postdates)
Composite outcome
Time Frame: 42 days (28 days neonatal period+2 weeks postdates)
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)
42 days (28 days neonatal period+2 weeks postdates)
Days of maternal admission for preterm labour
Time Frame: 2 weeks after expected date of birth
Number of days the mother was admitted to the hospital because of preterm labour
2 weeks after expected date of birth
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
complications to the mother related to preterm labour or the insertion of the stitch
2 weeks after expected date of birth

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

St George's, University of London

Investigators

  • Principal Investigator: Asma Khalil, St George's NHS Healthcare Trust

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 15, 2017

Primary Completion (Anticipated)

July 1, 2019

Study Completion (Anticipated)

December 1, 2019

Study Registration Dates

First Submitted

January 23, 2019

First Submitted That Met QC Criteria

January 23, 2019

First Posted (Actual)

January 28, 2019

Study Record Updates

Last Update Posted (Actual)

January 28, 2019

Last Update Submitted That Met QC Criteria

January 23, 2019

Last Verified

January 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 17.004

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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