Randomized Study of Pessary Versus Standard Management in Women With Increased Chance of Premature Birth

Study Overview
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Brief Summary
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The aim of the study is to determine the effect of cerclage pessary on the incidence of spontaneous delivery between randomization (at 20-24+6 weeks) and 33+6 weeks in asymptomatic women with singleton pregnancies found at routine mid-trimester screening to have a cervix of <25 mm in length and in twin pregnancies.

Detailed Description
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Prematurity is responsible for more than half of all neonatal deaths and whilst advances in neonatal care have dramatically improved survival of extremely premature infants, there remains a significant risk of handicap and disability in survivors and an associated social and economic burden. In singleton pregnancies the rate of spontaneous premature birth before 34 weeks is about 1% and the risk of spontaneous early delivery is inversely related to cervical length. The group with cervix of 1-15 mm accounted for 28% of all spontaneous deliveries before 34 weeks and those with cervix of 16-25 mm accounted for 21%. The rate of spontaneous premature birth before 34 weeks is about 13% in twin pregnancies. Potential methods for the prevention of preterm delivery include bed rest, cervical cerclage and prophylactic administration of progesterone. The prophylactic administration of progesterone beginning in mid-gestation to women who previously had a premature birth and in those with a short cervix has been shown to reduce the rate of spontaneous preterm birth before 34 weeks. On the other hand, randomized studies reported that, in twin pregnancies, bed rest was associated with a significant increase, rather than decrease, in the rate of early preterm delivery. There is some evidence that the rate of premature birth can be dramatically reduced by the insertion of a vaginal pessary (cerclage pessary, CE0482, MED/CERT ISO 9003 / EN 46003). This will be a multicenter trial in the UK and other countries. During routine ultrasound scan at 20-24 weeks of gestation for examination of fetal anatomy and growth, all women with twin pregnancy or with singleton pregnancy found to have a cervix of <25 mm in length and where the fetuses are found to be alive with no major abnormalities, severe twin to twin transfusion syndrome or severe fetal growth restriction in one of the fetuses (in the case of twin pregnancy), will be invited to participate in a randomized trial of standard management vs vaginal insertion of a cerclage pessary. For singleton pregnancy, in both arms the patients with cervical length <15 mm will be given prophylactic progesterone (200 mg vaginal capsule per night up to 34 weeks). Randomization and insertion of the pessary (in those allocated to this group) will be carried out within 5 days after the 20-24 weeks scan. The pessary will be removed by a simple vaginal examination at 37 weeks or earlier before medically indicated preterm induction of labor or elective cesarean section. The pessary will also be removed in women in preterm labor not responding to tocolytic therapy. In monochorionic twins some obstetricians advise that delivery is carried out at around 36 weeks.

Official Title
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Randomized Study of Pessary vs Standard Management in Women With Increased Chance of Premature Birth

Conditions
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Preterm Birth

Intervention / Treatment
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* Device: Vaginal pessary (CE0482, MED/CERT ISO 9003 / EN 46003)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women with singleton pregnancies and with a cervical length of 25 mm or less Women with twin pregnancies Exclusion Criteria: Major fetal abnormalities (defined as those that are lethal or require prenatal or postnatal surgery), fetal death, severe twin to twin transfusion syndrome or severe fetal growth restriction in one of the fetuses (in the case of twin pregnancy) diagnosed before randomization. Painful regular uterine contractions, history of ruptured membranes, or prophylactic cerclage before randomization. Patients who are unconscious, severely ill, mentally handicapped or under the age of 16 years.

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 45 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: A<br>Expectant management in twin pregnancy | |
| Experimental: B<br>Vaginal pessary treatment in twin pregnancy | Device: Vaginal pessary (CE0482, MED/CERT ISO 9003 / EN 46003)<br>* Inserted from randomization till 36-37 weeks of gestation<br>* Other names: Vaginal pessary, CE0482, MED/CERT ISO 9003 / EN 46003;|
| No Intervention: C<br>Expectant management in singleton pregnancy with short cervix; Women with cervix <15 mm will be commenced on vaginal progesterone | |
| Experimental: D<br>Vaginal pessary treatment in singleton pregnancy with short cervix; Women with cervix <15 mm will be commenced on vaginal progesterone | Device: Vaginal pessary (CE0482, MED/CERT ISO 9003 / EN 46003)<br>* Inserted from randomization till 36-37 weeks of gestation<br>* Other names: Vaginal pessary, CE0482, MED/CERT ISO 9003 / EN 46003;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary outcome measure will be spontaneous delivery from randomization to 33 weeks and 6 days (237 days) of gestation. |  | 10 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Low birth weight; Fetal or neonatal death; Major adverse outcomes (IVH, RDS, retinopathy of prematurity or necrotizing enterocolitis); Need for neonatal special care (ventilation, phototherapy, treatment for sepsis, blood transfusion) |  | Within the first year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Twins, Short cervix, Preterm birth, Vaginal pessary