Clinical trial NCT03058536: Progesterone and Cervical Pessary in Twins
Official title: Progesterone and Cervical Pessary in Twins : A Prospective and Randomized Study to Prevent Preterm Birth (PRECEPT)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Preterm Birth
Twin Pregnancy With Antenatal Problem
Keywords: twin short cervix pessary progesterone preterm birth
Lead sponsor: University of Sao Paulo
Sponsor class: OTHER
First posted: 2017-02-23
Enrollment: 312
Sex: FEMALE
Minimum age (years): 16
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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).
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Preterm birth
timeFrame: 5 months
Secondary outcomes:
measure: Neonatal Complications Rate
timeFrame: between birth and 28 days of age
measure: Months from Randomization to delivery interval
timeFrame: 6 months
Other outcomes:
Locations:
city: Sao Paulo
country: Brazil
facility: Hospital das Clinicas da FMUSP
Study officials:
affiliation: Hospital das Clínicas Universidade de São Paulo
name: Mario Henrique Burlacchini de Carvalho, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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