Preterm BirthPhase 3NCT00735137
Randomized Study of Pessary Versus Standard Management in Women With Increased Chance of Premature Birth
A Phase 3 study testing Vaginal pessary (CE0482, MED/CERT ISO 9003 / EN 46003) in people with Preterm Birth, run by King's College Hospital NHS Trust at 24 sites in 12 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Preterm Birth
- What is being tested?
- Vaginal pessary (CE0482, MED/CERT ISO 9003 / EN 46003)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,109 participants
- Where
- 24 sitesin 12 countries
- Study dates
- Aug 2008to Feb 2012
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 45 years
- Women only
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Women with singleton pregnancies and with a cervical length of 25 mm or less
- Women with twin pregnancies
Who cannot join
- 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.
Trial locations and contacts
24 sites in 12 countries.
24 sites in 12 countries
United Kingdom8 sites
Southend Hospital NHS Trust
Essex, SS0 0RY
The Medway Maritime Hospital NHS Trust
Kent, ME7 5NY
University College London Hospitals NHS Foundation Trust
London, NW1 2BU
The Lewisham Hospital NHS Trust
London, SE13 6LH
Queen Elizabeth Hospital NHS Trust
London, SE18 4QH
King's College Hospital NHS Trust
London, SE5 9RS
Barking, Havering and Redbridge Hospitals NHS Trust
Romford, Essex, RM7 0AG
Heatherwood and Wexham Park Hospitals, Wexham Park Hospital
Slough, Berkshire, SL2 4HL
Spain3 sites
Hospital Universitario Virgen de las Nieves
Granada, 18014
Hospital Universitario Materno Infantil de Canarias
Las Palmas de Gran Canaria, Canary Islands, 35016
Virgen de La Arrixaca
Murcia
Brazil2 sites
Universidade Federal Fluminense - Hospital Universitário Antônio Pedro
Niterói, Rio de Janeiro, 24033-900
University of Campinas
São Paulo
Colombia2 sites
Hospital San Jose
Bogotá
Hospital Universitario San Vicente de Paúl
Medellín
Portugal2 sites
Maternidade Dr. Alfredo da Costa
Lisbon
Hospital San Teotonio
Viseu
Austria1 site
Medical University of Vienna-department of Obstetrics and Gynaecology
Vienna, 1090
About this study
Official title: 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.
Read the 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
- Being tested
- Vaginal pessary (CE0482, MED/CERT ISO 9003 / EN 46003)
- Keywords
- Twins, Short cervix, Preterm birth, Vaginal pessary
- Medical subject headings
- Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vaginal pessary (CE0482, MED/CERT ISO 9003 / EN 46003)Device
Also called Vaginal pessary, CE0482, MED/CERT ISO 9003 / EN 46003
Inserted from randomization till 36-37 weeks of gestation
| Study group | Role | What they receive |
|---|---|---|
| A | No intervention | Expectant management in twin pregnancy |
| B | Experimental | Vaginal pessary treatment in twin pregnancy Receives: Device: Vaginal pessary (CE0482, MED/CERT ISO 9003 / EN 46003) |
| C | No intervention | Expectant management in singleton pregnancy with short cervix; Women with cervix <15 mm will be commenced on vaginal progesterone |
| D | Experimental | Vaginal pessary treatment in singleton pregnancy with short cervix; Women with cervix <15 mm will be commenced on vaginal progesterone Receives: Device: Vaginal pessary (CE0482, MED/CERT ISO 9003 / EN 46003) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary outcome measure will be spontaneous delivery from randomization to 33 weeks and 6 days (237 days) of gestation.
Measured: 10 weeks
Secondary outcomes (1)
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)
Measured: Within the first year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2008 (estimated)
- Study startAug 2008
- Primary completionFeb 2012
- Study completionFeb 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Preterm BirthStudies of the same condition, open and under way.
- More trials run by King's College Hospital NHS TrustThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 2,109 participants (actual)
Sponsor and investigators
- Lead sponsor
- King's College Hospital NHS Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kypros H Nicolaides, Professor, Study director, Consultant,Director of the Department of Fetal Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00735137
- Sponsor's protocol ID
- 07/HW/10
- Other IDs
- ISRCTN01096902
- Status last verified
- Feb 2021
- First submitted
- 13 Aug 2008
- Last updated
- 12 Feb 2021
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Study of Pessary vs Standard Management in Women With Increased Chance of Premature Birth
- ClinicalTrials.gov ID
- NCT00735137
- Acronym / sponsor ID
- 07/HW/10
- Conditions
- Preterm Birth
- Keywords
- Twins, Short cervix, Preterm birth, Vaginal pessary
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2,109 participants (actual)
- Lead sponsor
- King's College Hospital NHS TrustUniversity, hospital or other
- Study start
- Aug 2008
- Primary completion
- Feb 2012 (actual)
- Study completion
- Feb 2012 (actual)
- First posted
- 14 Aug 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| A | No intervention | –Expectant management in twin pregnancy |
| B | Experimental | Device: Vaginal pessary (CE0482, MED/CERT ISO 9003 / EN 46003)Vaginal pessary treatment in twin pregnancy |
| C | No intervention | –Expectant management in singleton pregnancy with short cervix; Women with cervix <15 mm will be commenced on vaginal progesterone |
| D | Experimental | Device: Vaginal pessary (CE0482, MED/CERT ISO 9003 / EN 46003)Vaginal pessary treatment in singleton pregnancy with short cervix; Women with cervix <15 mm will be commenced on vaginal progesterone |
Who may qualify
- Ages
- 16 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (2 listed)
- Women with singleton pregnancies and with a cervical length of 25 mm or less
- Women with twin pregnancies
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vaginal pessary (CE0482, MED/CERT ISO 9003 / EN 46003)Also: Vaginal pessary, CE0482, MED/CERT ISO 9003 / EN 46003Inserted from randomization till 36-37 weeks of gestation | Device | B, D |
Primary outcome
The primary outcome measure will be spontaneous delivery from randomization to 33 weeks and 6 days (237 days) of gestation.
Time frame: 10 weeks
1 secondary outcome
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)
Time frame: Within the first year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2021.
- Click here for more information about this study: Randomized study of pessary vs standard management in women with increased chance of premature birthLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kypros H Nicolaides, Professor study director
Consultant,Director of the Department of Fetal Medicine
24 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Vaginal pessary (CE0482, MED/CERT ISO 9003 / EN 46003) in people with Preterm Birth, run by King's College Hospital NHS Trust at 24 sites in 12 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in United Kingdom, Spain, Brazil, Colombia, Portugal and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary outcome measure will be spontaneous delivery from randomization to 33 weeks and 6 days (237 days) of gestation. (time frame: 10 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2021.