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

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

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.

Study Overview

• Status: Completed
• Conditions: Preterm Birth
• Intervention / Treatment: Device: Vaginal pessary (CE0482, MED/CERT ISO 9003 / EN 46003)

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.

• Study Type: Interventional
• Enrollment (Actual): 2109
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Medical University of Vienna-department of Obstetrics and Gynaecology
• Brazil
  • Sao Paulo, Brazil
    • University of Campinas
  • Rio De Janeiro
    • Niteroi, Rio De Janeiro, Brazil, 24033-900
      • Universidade Federal Fluminense - Hospital Universitário Antônio Pedro
• Chile
  • Santiago, Chile
    • Hospital Clinico Universidad de Chile
• Colombia
  • Bogota, Colombia
    • Hospital San José
  • Medellin, Colombia
    • Hospital Universitario San Vicente de Paúl
• Germany
  • Berlin, Germany
    • Virchow Clinic Charite
• Hong Kong
  • Hong Kong, Hong Kong
    • Chinese University of Hong Kong
• India
  • Bogulkunta, India, 500001
    • Fernandez Hospital, Bogulkunta,
• Italy
  • Lombardy
    • Como, Lombardy, Italy, 22100
      • Ospedale Valduce
• Portugal
  • Lisbon, Portugal
    • Maternidade Dr. Alfredo da Costa
  • Viseu, Portugal
    • Hospital San Teotonio
• Slovenia
  • Ljubljana, Slovenia
    • University Medical Centre Ljubljana
• Spain
  • Granada, Spain, 18014
    • Hospital Universitario Virgen de las Nieves
  • Murcia, Spain
    • Virgen de la Arrixaca
  • Islas Canarias
    • Las Palmas de Gran Canaria, Islas Canarias, Spain, 35016
      • Hospital Universitario Materno Infantil de Canarias
• United Kingdom
  • Essex, United Kingdom, SS0 0RY
    • Southend Hospital NHS Trust
  • Kent, United Kingdom, ME7 5NY
    • The Medway Maritime Hospital NHS Trust
  • London, United Kingdom, NW1 2BU
    • University College London Hospitals NHS Foundation Trust
  • London, United Kingdom, SE5 9RS
    • King's College Hospital NHS Trust
  • London, United Kingdom, SE13 6LH
    • The Lewisham Hospital NHS Trust
  • London, United Kingdom, SE18 4QH
    • Queen Elizabeth Hospital NHS Trust
  • Berkshire
    • Slough, Berkshire, United Kingdom, SL2 4HL
      • Heatherwood and Wexham Park Hospitals, Wexham Park Hospital
  • Essex
    • Romford, Essex, United Kingdom, RM7 0AG
      • Barking, Havering and Redbridge Hospitals NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 45 years (ADULT, CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
NO_INTERVENTION: A; Expectant management in twin pregnancy
EXPERIMENTAL: B; Vaginal pessary treatment in twin pregnancy	Device: Vaginal pessary (CE0482, MED/CERT ISO 9003 / EN 46003); Inserted from randomization till 36-37 weeks of gestation; Other Names: Vaginal pessary, CE0482, MED/CERT ISO 9003 / EN 46003
NO_INTERVENTION: C; Expectant management in singleton pregnancy with short cervix; Women with cervix <15 mm will be commenced on vaginal progesterone
EXPERIMENTAL: D; 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); Inserted from randomization till 36-37 weeks of gestation; Other Names: Vaginal pessary, CE0482, MED/CERT ISO 9003 / EN 46003

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: King's College Hospital NHS Trust
• Investigators: Study Director: Kypros H Nicolaides, Professor, Consultant,Director of the Department of Fetal Medicine

Publications and helpful links

Helpful Links

• Click here for more information about this study: Randomized study of pessary vs standard management in women with increased chance of premature birth

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (ACTUAL): February 1, 2012
• Study Completion (ACTUAL): February 1, 2012

Study Registration Dates

• First Submitted: August 13, 2008
• First Submitted That Met QC Criteria: August 13, 2008
• First Posted (ESTIMATE): August 14, 2008

Study Record Updates

• Last Update Posted (ACTUAL): February 12, 2021
• Last Update Submitted That Met QC Criteria: February 10, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Short cervix; Preterm birth; Twins; Vaginal pessary
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth
• Other Study ID Numbers: 07/HW/10; ISRCTN01096902