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

Preterm Birth Clinical Trial

— ENCIRCLE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03818867
• Other study ID #: 17.004
• Status: Recruiting
• Phase: N/A
• Start date: May 15, 2017
• Est. completion date: December 2019

Study information

• Verified date: January 2019
• Source: St George's, University of London
• Contact: Asma Khalil
• Phone: 7917400164
• Email: akhalil[@]sgul.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 31
• Est. completion date: December 2019
• Est. primary completion date: July 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Emergencies
• Fetofetal Transfusion
• Premature Birth
• Preterm Birth
• Twin Pregnancy With Antenatal Problem
• Twin to Twin Transfusion Syndrome

Intervention

Procedure:
• Insertion of cervical cerclage
insertion of a stitch around the neck of the womb in order to provide extra support.

Locations

Country	Name	City	State
United Kingdom	St George's Hospital	London

Sponsors (1)

Lead Sponsor	Collaborator
St George's, University of London

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to delivery (from randomisation to birth).	Time between randomisation and delivery in days	2 weeks after expected date of birth
Secondary	Gestation at delivery	gestational age at delivery in weeks	2 weeks after expected date of birth
Secondary	Preterm birth before 28, 32 and 34 weeks' gestation	the proportion of women giving birth before 28, 32 and 34 weeks	2 weeks after expected date of birth
Secondary	Birthweight	birth weight in grams	42 days (28 days neonatal period+2 weeks postdates)
Secondary	Stillbirth	death of the fetus (after 24 weeks) and before birth	42 days (28 days neonatal period+2 weeks postdates)
Secondary	Neonatal death	the death of a baby within the first 28 days of life	42 days (28 days neonatal period+2 weeks postdates)
Secondary	Survival to discharge	the proportion of the babies surviving until discharge from the hospital after birth	42 days (28 days neonatal period+2 weeks postdates)
Secondary	Days of admission to the neonatal intensive care unit	Number of days the baby was admitted in the neonatal intensive care unit	42 days (28 days neonatal period+2 weeks postdates)
Secondary	Composite outcome	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)
Secondary	Days of maternal admission for preterm labour	Number of days the mother was admitted to the hospital because of preterm labour	2 weeks after expected date of birth
Secondary	Maternal morbidity (de?ned as thromboembolic complications, chorioamnionitis, urinary tract infection treated with antibiotics, pneumonia, endometritis, eclampsia, HELLP syndrome, death, or any other significant morbidity)	complications to the mother related to preterm labour or the insertion of the stitch	2 weeks after expected date of birth