Clinical trial NCT04147117: Cervical Pessary to Prevent Preterm Singleton Birth in High Risk Population
Official title: Cervical Pessary to Prevent Preterm Singleton Birth in High Risk Population
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Preterm Birth
Keywords: Preterm Birth
Cervical Pessary
Obstetrical history
Cervical length
Lead sponsor: Hospital Sant Joan de Deu
Sponsor class: OTHER
First posted: 2019-10-31
Enrollment: 214
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: DESIGN: Observational prospective study. INCLUSION CRITERIA: All women are 18 years old of age or older with high risk for preterm birth, based on clinical history, and between 18.0 weeks and 23.6 weeks of pregnancy. SAMPLE SIZE: 214 asymptomatic high risk pregnant women.

METHODOLOGY: Patient selection, obtaining of informed consent, randomization for cervical placement of pessary. Current follow-up until delivery. Pessary is removed at 37 week or before in some specific situations.

MAIN OUTCOME: sPTB \<370 weeks of gestation. SECONDARY OUTCOMES: Pregnancy outcomes and a neonatal composite morbidity. EXPECTED RESULTS: Cervical pessary reduces sPB below 37 weeks in high risk of preterm birth population.

Detailed description: Spontaneous preterm birth (sPB) is still a leading cause of neonatal and infant death and responsible of neonatal morbidity as cerebral palsy. In spite of improvements of neonatal care, rates of preterm birth have not changed in the recent 10 years.

Clinical risk factors for preterm birth include: 1) Demographic characteristics such a low socioeconomic status, poor antenatal care, malnutrition or extremes in maternal age; 2) Behavioral factors including smoking, illicit drug abuse, alcohol consumption or heavy physical work; 3) Obstetric history including uterine malformation, previous preterm labor or preterm rupture of membranes (PROM), previous cervical surgery, late miscarriage \>16-17 weeks; 4) Aspects of the current pregnancy as multiple pregnancy, genital tract bleeding or infection, Preterm Rupture of Membranes (PROM), short cervix and others.

In nulliparous women with no previous pregnancies or fetal losses \>16 weeks, screening based on clinical history (maternal racial origin, age, height, smoking status and method of conception) could detect about 20% of sPB. In women with previous pregnancies at or beyond 16 weeks the detection rate is doubled by incorporating obstetric history.

The risks for women with a previous spontaneous preterm birth with a normal cervix in pregnancy are not negligible. It has been suggested that there is a continuum risk dependent on absolute cervical length while other authors showed that absolute length of cervix above 25mm had little impact on the risk of preterm birth before 35 weeks. A posterior study has not identified any clinical or obstetric risk factors in high-risk women with cervical length greater than 25mm that could help to identify those who will subsequently have a spontaneous preterm birth.

The risk of preterm birth is inversely related to cervical length (CL) as measured by ultrasound. Current options for the management of short cervix in singleton pregnancies are: vaginal progesterone, with proved benefit; cervical cerclage in high risk and short cervix, and cervical pessary.

Cervical pessary is a silicone ring with a smaller diameter to be fitted around the cervix and a larger diameter to fix the device to the pelvic floor. It modifies the direction of the cervix to the posterior vaginal wall.

Three randomized trials involving women with singleton low risk pregnancies and short cervix provided controversial results regarding the effect of cervical pessary on the rate of sPB before 34 weeks; in one trial, involving 380 women, the rate of this outcome was significantly lower with a pessary than with no pessary (6% vs 27%); in another trial, involving 108 women, there was no significant effect (9.4% vs 5.5%, respectively) and in the largest trial, involving 935 women, no benefits were found (12.9% vs 11.3%, respectively).

Nowadays high-risk population with normal cervix is managed by cervical length surveillance and physical activity restriction, as progesterone has not a proved benefit in women at risk because of previous history but normal cervix.

Cervical pessary has not been tested specifically in high risk population. In PECEP study a total number of 42 patients (11% of each group) had at least one previous preterm birth. Authors did not report differences in the risk of preterm birth before 34 weeks in this subgroup. In Nicolaides study, 154 patients had previous birth before 37 weeks: 70 were treated with pessary and 84 with expectant management. The reported risk of birth before 34 weeks was 10.1% and 19.5%, respectively. In spite of the increased risk in expectant group, these differences were not significant (OR 0.47 (0.18-1.21) p= 0.12). In both trials, women included has short cervix.

Even that group of women with previous preterm birth were included in the previous trials, pessary has not been proved in a specific group of population with previous history of preterm birth or uterine-cervical factors. Therefore, there is a lack of information in this topic.

Eligibility criteria: Inclusion Criteria:

* Singleton pregnancy.
* Age \> 18 years old.
* Gestational age between 18.0 -23.6 weeks of gestation.
* Asymptomatic singleton pregnancies, with at least one of the following:

  * Previous spontaneous preterm delivery or PPROM (23 - 34.6 weeks).
  * Previous spontaneous second trimester miscarriage (16.0-22.6 weeks).
  * Previous surgery on uterine cervix.
  * Uterine malformation.
* Able to sign informed consent form.

Exclusion Criteria:

* Congenital, chromosomal abnormalities or stillbirth in current pregnancy before randomization.
* Women with an obstetrical history of iatrogenic preterm birth indicated for maternal or fetal conditions.
* Symptomatic high-risk women or preterm prelabor rupture of membranes (PROM) in the current pregnancy.
* Pregnant women with an indication of prophylactic cervical cerclage due to her own obstetrical history.
* Pregnant women with an indication to perform a cervical cerclage, prior to study inclusion.
* Cerclage in situ.
* Active vaginal bleeding.

Primary outcomes:
measure: Spontaneous preterm birth before 37 weeks of gestation
timeFrame: 3 years
Secondary outcomes:
measure: Preterm birth 34 weeks
timeFrame: 5 months
measure: Preterm birth 28 weeks
timeFrame: 5 months
measure: PPROM before 34 weeks
timeFrame: 5 months
measure: Threatened preterm labor
timeFrame: 5 months
measure: Cervical trauma
timeFrame: 5 months
measure: Pessary tolerance
timeFrame: 5 months
measure: Infection
timeFrame: 5 months
measure: Progesterone co-treatment
timeFrame: 5 months
measure: Choriomanionitis
timeFrame: 5 months
measure: Maternal mortality or morbidity
timeFrame: 5 months
measure: Neonatal birthweight
timeFrame: 5 months
measure: Neonatal outcomes APGAR
timeFrame: 5 months
measure: Neonatal outcomes umbilical artery pH
timeFrame: 5 months
measure: Neonatal outcomes NICU
timeFrame: 5 months
measure: Neonatal outcomes for respiratory support
timeFrame: 5 months
measure: Neonatal outcomes SDR
timeFrame: 5 months
measure: Neonatal outcomes IVH
timeFrame: 5 months
measure: Neonatal outcomes NEC
timeFrame: 5 months
measure: Neonatal outcomes. Death
timeFrame: 5 months
measure: Neonatal outcomes. Sepsis
timeFrame: 5 months
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Déu. BCNatal | Barcelona Center for Maternal Fetal and Neonatal Medicine | Hospital Clínic - Hospital Sant Joan de Déu
Study officials:
affiliation: BCNatal | Hospital Sant Joan de Déu - Hospital Clínic
name: Silvia Irene Ferrero Martínez, MD,PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: BCNatal | Hospital Clínic- Hospital Sant Joan de Déu
name: Montse Palacio Riera, MD,PhD
role: STUDY_DIRECTOR
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