Cervical Pessary vs Vaginal Progesterone in Preventing Preterm Birth Among Women Presenting With Short Cervix: An Open-label Randomized Controlled Trial

June 9, 2015 updated by: Hillel Yaffe Medical Center

Cervical Pessary vs. Vaginal Progesterone in Preventing Preterm Birth Among Women Presenting With Short Cervix: An Open-label Randomized Controlled Trial

The purpose of this randomized control trial is to determine whether cervical pessary plus vaginal progesterone is superior to vaginal progesterone alone in decreasing preterm delivery rate, and improving perinatal outcome, among women presenting with an asymptomatic mid-pregnancy short cervix, in singleton and twin gestations.

All women with singleton or twin pregnancies undergoing routine ultrasonography up to 24 completed weeks of gestation (for examination of fetal anatomy and growth) and diagnosed with cervical length of ≤25 mm in singleton, or ≤38 mm in twins, will be invited to participate in the clinical trial.

Women who meet eligible criteria will be invited to participate in the clinical trial.

Women will be randomly assigned into one of the following groups: group A (vaginal progesterone) or group B (vaginal progesterone + pessary).

Follow-up visits for ultrasound assessment of fetal growth and cervical length will be carried out every two weeks until 37 weeks of gestation.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Preterm birth represents a major challenge to obstetricians as well as healthcare policy makers. It is a leading cause of perinatal morbidity and mortality among singleton and multiple pregnancies. In the USA, the frequency of of preterm births (<37 completed weeks of gestation) is 10-13% in singleton pregnancies, and 57% in twins and these rate have not substantially changed in the last decade.

A short cervix (<25 mm) measured by vaginal ultrasonography during mid pregnancy (18-24 weeks of gestation) is a powerful predictor of spontaneous preterm birth (PTB). The relative risk for PTB increases as the cervical length decreases.

The two most studied treatment options in cases of short cervix at mid pregnancy are vaginal progesterone preparations, and cervical cerclage. Vaginal progesterone, given either as 90 mg gel or 200 mg suppository, was repeatedly shown to significantly reduce PTB rates and perinatal morbidity and mortality in women found to have a short cervix (20 mm or less) at 24 weeks gestation.

Progesterone were proven ineffective for the prevention of preterm birth in cases of multiple gestations, present preterm labor, or preterm premature rupture of membranes.

Cerclage may be considered an alternative for vaginal progesterone only in women with history of PTB that are found to have a short cervix in the present pregnancy (cervical length <25 mm before 24 weeks of gestation). According to a recently published indirect meta-analysis, vaginal progesterone and cerclage are equally efficacious in the prevention of PTB in women with a singleton gestation, mid trimester sonographic short cervix, and a history of previous preterm birth.

Unfortunately, vaginal progesterone and cervical cerclage were not proven effective for the prevention of PTB in twin gestations. Moreover, cervical cerclage in this context may even lead to worse outcome compared to conservative treatment. Additionally, in contrast to singleton pregnancies, neither vaginal progesterone nor injections of 17alpha-hydroxyl-progesterone caproate prevented neonatal morbidity or preterm birth in multiple pregnancies. One meta-analysis suggested that vaginal progesterone for mid trimester short cervix in twin gestation may improve neonatal outcome without prolonging the pregnancy.

Cervical Pessary is a renovated method, currently being studied for its clinical advantages over the existing available treatments in the context of midtrimester asymptomatic short cervix in singleton and twin gestation.

The largest multicenter randomized controlled trial (RCT) on pessary use in selected women screened by Trans Vaginal Sonography (TVS) excluded women who had one of the following: a known major fetal anomaly, painful regular uterine contractions, active vaginal bleeding, ruptured membrane, placenta previa, or a history of cone biopsy or cervical cerclage in situ. The conclusion of this study was that in women with a short cervical length (>25mm) between 18-22 weeks, the use of cervical pessary significantly prolonged pregnancy and reduced the rate of poor neonatal outcome compared with control, untreated patients. A second, and smaller, RCT failed to corroborate the findings previously described. In this study, the mean gestational age at delivery was 38.1 weeks in the pessary group compared to 37.8 weeks in the expectant management group, with no significant differences in the rates of delivery before 28, 34 or 37 weeks of gestation.

Currently, no published RCT compared the efficacy of the cervical pessary with that of cerclage or progestogens for short cervix in singletons or twins. A retrospective comparison between the methods has shown no significant differences in the rates of perinatal loss, neonatal morbidity or PTB for singleton pregnancies (apart from higher rate of PTB at <34 weeks' gestation in the vaginal progesterone vs the pessary group).

In 2003, the first case control study in twin pregnancies and cervical pessary was conducted. Twenty-three women with short cervical length (<25 mm) prior to 24 weeks of gestation were treated with pessary and matched with 23 controls. The mean gestational age at delivery was 35+6 weeks in the pessary group and 33+2 weeks in the control group (p value=0.02).

A large RCT published in 2013 included 403 women with twin pregnancies who were randomized to either prophylactic pessary or expectant management. Women with all cervical length were included. The authors concluded that prophylactic use of pessary in unselected twin pregnancies did not prolong pregnancy or reduce poor perinatal outcome. However, in a sub group analysis of women with a cervical length less than 38 mm (<25th percentile), a significantly lower incidence of poor neonatal outcomes, delivery before 32 weeks, and neonatal mortality was found in the pessary group.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
430

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Diagnosed to be pregnant at up to 24+0 weeks of gestation, with a cervical length measurement of ≤25 mm with a singleton pregnancy, or ≤38 mm in twins pregnancy.
  • Does not meet with maternal/fetal/membrane/placental factors detailed in the exclusion criteria.
  • Willingness to comply with the protocol for the duration of the study.
  • Have signed an informed consent.

Exclusion Criteria:

  • Fetal factors: major fetal abnormalities, death of one or both of the fetuses, twins- twin-to-twin transfusion syndrome, and severe growth retardation.
  • Maternal factors: prophylactic cervical cerclage in situ, painful regular uterine contractions, active labor, active vaginal bleeding, maternal age under 18, uterine abnormalities (i.e. two cervices), and severe uterine prolapse.
  • Membranes and placental factors: placenta previa, ruptured membranes.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Progesterone
200 mg daily of vaginal progesterone suppositories (Utrogestan)
Drug: Progesterone
200 mg daily of vaginal progesterone suppositories (Utrogestan)
Experimental: Progesterone plus Experimental device
Experimental device + 200 mg daily progesterone vaginal suppositories (Utrogestan)
Device: Pessary
Two optional pessary sizes with the following dimensions: 65/17/35 or 70/17/35 and 200 mg daily progesterone vaginal suppositories (Utrogestan)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
preterm birth before 34 weeks of gestation rate in singleton pregnancies
Time Frame: up to 20 weeks from recruitment
up to 20 weeks from recruitment
preterm birth before 32 weeks of gestation rate in twin pregnancies
Time Frame: up to 20 weeks from recruitment
up to 20 weeks from recruitment

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Other preterm birth age before 34, 28 weeks in twin pregnancies
Time Frame: up to 20 weeks from recruitment
up to 20 weeks from recruitment
Neonatal/perinatal complications rate
Time Frame: up to 20 weeks from recruitment
Respiratory Distress Syndrome (RDS), necrotizing enterocolitis, intraventricular hemorrhage, proven neonatal sepsis, retinopathy of prematurity, bronchopulmonary dysplasia, periventricular leukomalacia, fetal death, neonatal death. Apgar score <7 at 5 minutes, birth weight <1500 g and <2500 g, use of mechanical ventilation, congenital anomaly.
up to 20 weeks from recruitment
Maternal Adverse events
Time Frame: up to 20 weeks from recruitment
vaginal discharge, vaginal pruritus, discontinuation of treatment because of adverse events, threatened preterm labor.
up to 20 weeks from recruitment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hillel Yaffe Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2015

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2018

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 4, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 9, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 12, 2015

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 12, 2015

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 9, 2015

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 0096-14-HYMC

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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