Cerclage for the Reduction of Extreme Preterm Birth in Twin Pregnancies With a Short Cervix or Dilatation

Study Overview
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Brief Summary
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The goal of this clinical trial is to assess the effectiveness of a cerclage in women with a twin pregnancy with a midpregnancy short cervix or cervical dilatation compared to standard treatment (no cerclage) in the prevention of extreme preterm birth < 28 weeks of gestational age. The main question it aims to answer is: What is the effectiveness of a cerclage in women with a twin pregnancy with a midpregnancy short cervix or cervical dilatation compared to standard treatment (no cerclage) in the prevention of extreme preterm birth < 28 weeks of gestational age? Participants will be randomly assigned to the intervention (cerclage) or comparison (no cerclage) group.

Detailed Description
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Rationale: In the Netherlands, 250 women with a twin pregnancy deliver at < 28 weeks per year, resulting in 157 perinatal deaths. A vaginal cerclage could be an effective surgical method to reduce cervical insufficiency and with that preterm birth, but the evidence regarding its effectiveness on extreme preterm birth and (long term) neonatal outcome is lacking. Objective: To assess the effectiveness of a cerclage in women with a twin pregnancy with a midpregnancy short cervix or cervical dilatation compared to standard treatment (no cerclage) in the prevention of extreme preterm birth < 28 weeks of gestational age. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: A vaginal cerclage is a minor and safe surgical procedure commonly performed in singleton pregnancies with a short cervix and a previous preterm birth in all the participating centers, thus there is experience in the participating hospitals. The results of this study will show whether a vaginal cerclage reduces extreme preterm birth in women with twin pregnancy and a short cervix, and its accompanying perinatal complications. If proven effective, the implementation of this intervention will have a huge impact on the lifelong health of these children and their families.

Official Title
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The Effectiveness of Cerclage for the Reduction of Extreme Preterm Birth and Perinatal Mortality in Twin Pregnancies With a Short Cervix or Dilatation

Conditions
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Preterm Birth

Intervention / Treatment
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* Procedure: Vaginal cerclage


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women (> 16 years of age) with a twin pregnancy and: an asymptomatic short cervix at routine ultrasound investigation (below 24 weeks of gestation) OR cervical dilatation (below 24 weeks of gestation) Exclusion Criteria: Women with a mono-amniotic twin pregnancy Women with twin pregnancy in which one or both children are diagnosed with a major structural, congenital or chromosomal abnormality that is likely to influence the composite adverse neonatal outcome. Women with dilatation of the cervix and signs of clinical intra-uterine infection, defined by the presence of fever ≥ 38 degrees Celsius. Women with overt symptoms of preterm labour at time of measurement of short cervix (regular contractions, PPROM, recurrent blood loss). Women with a placenta previa, defined as a placenta position covering the internal ostium of the cervix. Women who do not master the Dutch of English language and therefore not able to give written consent

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: International, multicenter randomized controlled trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cerclage<br>A vaginal cerclage is a short and minor surgical procedure performed under general or regional anesthesia. An unabsorbable suture is placed around/through the cervix to close the cervical canal and to increase its firmness, in order to reduce cervical insufficiency. | Procedure: Vaginal cerclage<br>* A vaginal cerclage is a short and minor surgical procedure performed under general or regional anesthesia. An unabsorbable suture is placed around/through the cervix to close the cervical canal and to increase its firmness, in order to reduce cervical insufficiency.<br>|
| No Intervention: Standard care<br>The comparator will be standard treatment according to the current Dutch (NVOG) guideline from 2018, which is to not perform or offer an intervention such as vaginal cerclage. This is in line with the standard care in the participating hospitals in Belgium. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of extreme preterm birth |  | <28 weeks of gestation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Preterm birth | Indicated and spontaneous | <24, <32, <34 and <37 weeks | 
| Rate of Premature rupture of membranes |  | Up to 42 weeks of pregnancy | 
| Gestational age at delivery |  | At delivery | 
| Days on ventilation support | Neonatal | Up to 3 months corrected age | 
| Days in NICU | Neonatal | Up to 3 months corrected age | 
| Maternal quality of life assessed by the 'European Quality of life 5-Dimension 5-Level' score | The 'European Quality of life 5-Dimension 5-Level' score consists of five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) that are rated using five levels (no problems (1), slight problems (2), moderate problems (3), severe problems (4), extreme problems (5)). A unique health state is defined by combining one level from each of the five dimensions. Each state is referred to by a 5-digit code, The best score is 11111 and the worst score is 55555. | Up to 3 months corrected age | 
| Rate of maternal outcomes | Sepsis, need for antibiotics, need to remove cerclage in operation room, mode of delivery (% caesarean delivery). | Up to 3 months corrected age | 
| Adverse neonatal outcome | A composite for adverse neonatal outcome (including bronchopulmonary dysplasia, periventricular leucomalacia > grade 1, intraventricular hemorrhage > grade 2, necrotizing enterocolitis > stage 2, retinopathy of prematurity > stage 2, proven sepsis and perinatal death) | Up to 3 months corrected age | 
| Number of neonates with bronchopulmonary dysplasia |  | Up to 3 months corrected age | 
| Number of neonates with periventricular leucomalacia > grade 1 |  | Up to 3 months corrected age | 
| Number of neonates with intraventricular hemorrhage > grade 2 |  | Up to 3 months corrected age | 
| Number of neonates with necrotizing enterocolitis > stage 2 |  | Up to 3 months corrected age | 
| Number of neonates with retinopathy of prematurity > stage 2 |  | Up to 3 months corrected age | 
| Number of neonates with proven sepsis |  | Up to 3 months corrected age | 
| Perinatal death |  | Up to 3 months corrected age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Preterm birth, Twin pregnancy, Cerclage