Progesterone and Cervical Pessary in Twins

Study Overview
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Brief Summary
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The aim of this randomized control trial is to determine wheter cervical pessary plus vaginal progesterone (400mg) reduce preterm birth less than 34 weeks of gestacion and improve perinatal outcome, among women presenting asyntomatic short cervix, in twin pregnancy.

Detailed Description
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The frequency of twin pregnancies has increased significantly, especially because of the assisted reproduction and advanced maternal age at conception. The twin pregnancies are responsible for 25 % of all preterm birth. Consequently, twin pregnancies are more associated with perinatal mortality and morbidity when compared to single pregnancies. Additionally, the short cervix (< 25 mm) in singleton and twin pregnancies are associated with significantly increased preterm birth. Randomized controlled trials in singleton pregnancies reported that profilatic cervical cerclage and vaginal progesterone reduce significantly the rate of early preterm birth. In twin pregnancies, vaginal progesterone and profilatic cerclage have been shown to be ineffective in prevention of preterm birth. However, two individual pacient data meta-analyses reported in a subgroup of women with twin pregancies and short cervix, that vaginal progesterone reduce significantly adverse neonatal outcomes. Nowadays, the effet of cervical pessary is contraditory, mainly in women with short cervix. This is a randomized prospective trial at São Paulo University Medical School. This trial will involve 312 women with twins pregnancies and short cervix between 16 and 27 weeks and 6 days of gestacional age. Women with twin pregnancy and short cervix ( defined according to the gestacional age ) will be assigned randomly to daily vaginal progesterone (400mg) combined with insertion of cervical pessary, isolated use of daily vaginal progesterone (400mg) isolated insertion of cervical pessary or expectant management (no intervention). The primary outcome is to compare the rate of spontaneous delivery < 34 weeks of gestacion between groups.The secondary outcome is to compare the neonatal adverse outcome between the groups. The aim of this study is to test the hypothesis that the insertion of a cervical pessary combined with vaginal progesterone, in twin pregnancies with short cervix would reduce the spontaneus preterm birth < 34 weeks' gestation.

Official Title
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Progesterone and Cervical Pessary in Twins : A Prospective and Randomized Study to Prevent Preterm Birth (PRECEPT)

Conditions
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Preterm Birth, Twin Pregnancy With Antenatal Problem

Intervention / Treatment
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* Device: Arabin Pessary
* Drug: Vaginal Progesterone
* Other: Arabin Pessary and Progesterone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Twin pregnancy ( dichorionic or monochorionic diamniotic) Both fetuses alive Asymptomatic short cervix according to gestational age ( measurement less or equal 30 mm between 16 weeks + 0 day and 22 weeks + 0 day, less or equal 25 mm between 22 weeks + 1 day and 24 weeks + 0 day and less or equal 20 mm between 24 weeks + 1 day and 27 weeks + 6 days) Gestational age between 16 to 27weeks and 6 days Intact membranes Informed consent Exclusion Criteria: Monoamniotic twins Twin Twin transfusion syndrome Rupture membranes Major malformation or chromosomal abnormality at least one fetus Women with Cervical cerclage in the current pregnancy Ballooning of membranes outside the cervix into the vagina Placenta previa Treatment with progesterone before randomization Allergy of the excipientes of the micronized progesterone Labor Severe hepatic disfunction, porphyria, otosclerosis, severe depression Use of drugs that interfere the effects of progesterone

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 312 twin pregnant women with short cervix between 16 and 27 weeks and 6 days of gestacional age will be randomized in four groups: daily 400mg vaginal progesterone combined with insertion of cervical pessary; isolated use of daily 400mg vaginal progesterone, isolated insertion of cervical pessary or expectant management (no intervention).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Progesterone<br>400 mg micronized vaginal progesterone daily from randomization to 36 weeks | Drug: Vaginal Progesterone<br>* Treatment with 400 mg micronized progesterone daily, until the day of randomization to 36 weeks of pregnancy.<br>* Other names: Utrogestan;|
| Active Comparator: Arabin Pessary and Progesterone<br>Arabin Pessary and Natural Micronized Progesterone 400 mg micronized vaginal progesterone daily from randomization to 36 weeks The device will be placed at randomization and will be removed during the 36th week of gestacional (or earlier if indicated) in combination with vaginal progesterone. | Other: Arabin Pessary and Progesterone<br>* Arabin Pessary and Progesterone The cervical pessary will be inserted at the randomization and removed during the 36 week of pregnancy, unless labour occurs sooner. Treatment with 400 mg Micronized progesterone daily, until the day of randomization to 36 weeks of pregnancy.<br>|
| Active Comparator: Arabin Pessary<br>The device will be placed at randomization and will be removed during the 36th week of gestacional (or earlier if indicated) without vaginal progesterone use. | Device: Arabin Pessary<br>* The cervical pessary will be inserted at the randomization and removed during the 36 week of pregnancy, unless labour occurs sooner.<br>|
| No Intervention: No intervention<br>Expectant management | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Preterm birth | Rate of preterm birth before 34 weeks gestation | 5 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neonatal Complications Rate | Includes necrotizing enterocolitis, intraventricular hemorrhage (grade 3 or higher), respiratory distress syndrome, retinopathy, sepsis, use of mechanical ventilation, time of hospitalization, and neonatal death. | between birth and 28 days of age | 
| Months from Randomization to delivery interval | Randomization may begin at 16 weeks, and most patient will be delivered between 36 and 38 weeks gestation. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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twin short cervix pessary progesterone preterm birth