Preterm Birth Clinical Trial
Official title:
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.
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.
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Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
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