Clinical trial NCT00735137: Randomized Study of Pessary Versus Standard Management in Women With Increased Chance of Premature Birth
Official title: Randomized Study of Pessary vs Standard Management in Women With Increased Chance of Premature Birth
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Preterm Birth
Keywords: Twins
Short cervix
Preterm birth
Vaginal pessary
Lead sponsor: King's College Hospital NHS Trust
Sponsor class: OTHER
First posted: 2008-08-14
Enrollment: 2109
Sex: FEMALE
Minimum age (years): 16
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: The primary outcome measure will be spontaneous delivery from randomization to 33 weeks and 6 days (237 days) of gestation.
timeFrame: 10 weeks
Secondary outcomes:
measure: 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)
timeFrame: Within the first year
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Medical University of Vienna-department of Obstetrics and Gynaecology
city: Niteroi
country: Brazil
facility: Universidade Federal Fluminense - Hospital Universitário Antônio Pedro
state: Rio De Janeiro
city: Sao Paulo
country: Brazil
facility: University of Campinas
city: Santiago
country: Chile
facility: Hospital Clinico Universidad de Chile
city: Bogota
country: Colombia
facility: Hospital San Jose
city: Medellin
country: Colombia
facility: Hospital Universitario San Vicente de Paúl
city: Berlin
country: Germany
facility: Virchow Clinic Charite
city: Hong Kong
country: Hong Kong
facility: Chinese University of Hong Kong
city: Bogulkunta
country: India
facility: Fernandez Hospital, Bogulkunta,
city: Como
country: Italy
facility: Ospedale Valduce
state: Lombardy
city: Lisbon
country: Portugal
facility: Maternidade Dr. Alfredo da Costa
city: Viseu
country: Portugal
facility: Hospital San Teotonio
city: Ljubljana
country: Slovenia
facility: University Medical Centre Ljubljana
city: Las Palmas de Gran Canaria
country: Spain
facility: Hospital Universitario Materno Infantil de Canarias
state: Islas Canarias
city: Granada
country: Spain
facility: Hospital Universitario Virgen de las Nieves
city: Murcia
country: Spain
facility: Virgen de La Arrixaca
city: Slough
country: United Kingdom
facility: Heatherwood and Wexham Park Hospitals, Wexham Park Hospital
state: Berkshire
city: Romford
country: United Kingdom
facility: Barking, Havering and Redbridge Hospitals NHS Trust
state: Essex
city: Essex
country: United Kingdom
facility: Southend Hospital NHS Trust
city: Kent
country: United Kingdom
facility: The Medway Maritime Hospital NHS Trust
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust
city: London
country: United Kingdom
facility: The Lewisham Hospital NHS Trust
city: London
country: United Kingdom
facility: Queen Elizabeth Hospital NHS Trust
city: London
country: United Kingdom
facility: King's College Hospital NHS Trust
Study officials:
affiliation: Consultant,Director of the Department of Fetal Medicine
name: Kypros H Nicolaides, Professor
role: STUDY_DIRECTOR
References: