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

NCT ID: NCT00735137

Last Updated: 2021-02-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 2109 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-08-31
• Study Completion Date: 2012-02-29

Brief Summary

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

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.

Conditions

Preterm Birth

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

A

Expectant management in twin pregnancy

Group Type: NO_INTERVENTION

No interventions assigned to this group

B

Vaginal pessary treatment in twin pregnancy

Group Type: EXPERIMENTAL

Vaginal pessary (CE0482, MED/CERT ISO 9003 / EN 46003)

Intervention Type: DEVICE

Inserted from randomization till 36-37 weeks of gestation

C

Expectant management in singleton pregnancy with short cervix; Women with cervix \<15 mm will be commenced on vaginal progesterone

Group Type: NO_INTERVENTION

No interventions assigned to this group

D

Vaginal pessary treatment in singleton pregnancy with short cervix; Women with cervix \<15 mm will be commenced on vaginal progesterone

Group Type: EXPERIMENTAL

Vaginal pessary (CE0482, MED/CERT ISO 9003 / EN 46003)

Intervention Type: DEVICE

Inserted from randomization till 36-37 weeks of gestation

Interventions

Vaginal pessary (CE0482, MED/CERT ISO 9003 / EN 46003)

Inserted from randomization till 36-37 weeks of gestation

Intervention Type: DEVICE

Other Intervention Names

Vaginal pessary, CE0482, MED/CERT ISO 9003 / EN 46003

Eligibility Criteria

Inclusion Criteria

1. Women with singleton pregnancies and with a cervical length of 25 mm or less

2. Women with twin pregnancies

Exclusion Criteria

1. 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.

2. Painful regular uterine contractions, history of ruptured membranes, or prophylactic cerclage before randomization.

3. Patients who are unconscious, severely ill, mentally handicapped or under the age of 16 years.

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

King's College Hospital NHS Trust

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kypros H Nicolaides, Professor

Role: STUDY_DIRECTOR

Consultant,Director of the Department of Fetal Medicine

Locations

Medical University of Vienna-department of Obstetrics and Gynaecology

Vienna, , Austria

Universidade Federal Fluminense - Hospital Universitário Antônio Pedro

Niterói, Rio de Janeiro, Brazil

University of Campinas

São Paulo, , Brazil

Hospital Clinico Universidad de Chile

Santiago, , Chile

Hospital San Jose

Bogotá, , Colombia

Hospital Universitario San Vicente de Paúl

Medellín, , Colombia

Virchow Clinic Charite

Berlin, , Germany

Chinese University of Hong Kong

Hong Kong, , Hong Kong

Fernandez Hospital, Bogulkunta,

Bogulkunta, , India

Ospedale Valduce

Como, Lombardy, Italy

Maternidade Dr. Alfredo da Costa

Lisbon, , Portugal

Hospital San Teotonio

Viseu, , Portugal

University Medical Centre Ljubljana

Ljubljana, , Slovenia

Hospital Universitario Materno Infantil de Canarias

Las Palmas de Gran Canaria, Canary Islands, Spain

Hospital Universitario Virgen de las Nieves

Granada, , Spain

Virgen de La Arrixaca

Murcia, , Spain

Heatherwood and Wexham Park Hospitals, Wexham Park Hospital

Slough, Berkshire, United Kingdom

Barking, Havering and Redbridge Hospitals NHS Trust

Romford, Essex, United Kingdom

Southend Hospital NHS Trust

Essex, , United Kingdom

The Medway Maritime Hospital NHS Trust

Kent, , United Kingdom

University College London Hospitals NHS Foundation Trust

London, , United Kingdom

The Lewisham Hospital NHS Trust

London, , United Kingdom

Queen Elizabeth Hospital NHS Trust

London, , United Kingdom

King's College Hospital NHS Trust

London, , United Kingdom

Countries

Austria; Brazil; Chile; Colombia; Germany; Hong Kong; India; Italy; Portugal; Slovenia; Spain; United Kingdom

Other Identifiers

ISRCTN01096902

Identifier Type: -

Identifier Source: secondary_id

07/HW/10

Identifier Type: -

Identifier Source: org_study_id