Progesterone and Cervical Pessary in Twins (PRECEPET)

Mario Henrique Burlacchini de Carvalho

Status and phase: Unknown; Phase 3; Phase 2

Conditions: Twin Pregnancy With Antenatal Problem; Preterm Birth

Treatments: Drug: Vaginal Progesterone; Device: Arabin Pessary; Other: Arabin Pessary and Progesterone

Study type: Interventional

Funder types: Other

Identifiers

NCT03058536

1.847.411

Details and patient eligibility

About

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.

Full 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.

Enrollment: 312 estimated patients

Sex: Female

Ages: 16 to 50 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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312 participants in 4 patient groups

Progesterone

Active Comparator group

Description:

400 mg micronized vaginal progesterone daily from randomization to 36 weeks

Treatment:

Drug: Vaginal Progesterone

Arabin Pessary and Progesterone

Active Comparator group

Description:

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.

Treatment:

Other: Arabin Pessary and Progesterone

Arabin Pessary

Active Comparator group

Description:

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.

Treatment:

Device: Arabin Pessary

No intervention

No Intervention group

Description:

Expectant management