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

Sponsor

King's College Hospital NHS Trust (Other)

Overall Status

Completed

CT.gov ID

NCT00735137

Collaborator

(none)

2,109

Enrollment

Locations

Arms

Duration (Months)

87.9

Patients Per Site

2.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Preterm Birth	Device: Vaginal pessary (CE0482, MED/CERT ISO 9003 / EN 46003)	Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

2109 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

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

Study Start Date :

Aug 1, 2008

Actual Primary Completion Date :

Feb 1, 2012

Actual Study Completion Date :

Feb 1, 2012

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years to 45 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

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.

Contacts and Locations

Locations

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