Clinical trial NCT01643980: Prevention of Preterm Birth in Pregnant Women at Risk Identified by Ultrasound: Evaluation of Two Treatment Strategies
Official title: Prevention of Preterm Birth in Pregnant Women at Risk Identified by Ultrasound: Evaluation of Two Treatment Strategies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Early Onset of Delivery Before 37 Weeks
Lead sponsor: Puerta de Hierro University Hospital
Sponsor class: OTHER
First posted: 2012-07-18
Enrollment: 254
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The preterm birth is considered as a main problem in the modern obstetrics, being the responsible of greatest of 50% neonatal morbimortality and heavy costs. Despite the significant medical advances, the rate of prematurity has not declined over the past 40 years and even continues to rise in the developed countries. In order to decrease the prematurity is necessary that two premises: to identify the pregnant women at risk of preterm birth, and dispose of useful measures aimed at prolonging the pregnancy and therefore avoid preterm delivery. The investigators propose a clinical trial with the objective to identify effective strategies to reduce the premature birth (34 weeks and earlier) rate in the population of pregnant women at risk for premature birth, which will be identified by ultrasound during the second trimester of their pregnancy.

The investigators intend to compare two accepted strategies: administration of progesterone (vaginally) or the placement of vaginal pessaries. These 2 strategies are affordable, easy to apply, and they present very few maternal-fetal secondary effects.

Detailed description: The preterm birth is considered as a main problem in the modern obstetrics, being the responsible of greatest of 50% neonatal morbimortality and heavy costs. Despite the significant medical advances, the rate of prematurity has not declined over the past 40 years and even continues to rise in the developed countries. In order to decrease the prematurity is necessary that two premises: to identify the pregnant women at risk of preterm birth, and dispose of useful measures aimed at prolonging the pregnancy and therefore avoid preterm delivery. Since 1990, many published articles describe the sonographic measurement of the cervix from the week 16 as method of population screening to detect women at risk. Several studies provide evidence about an inverse relationship between the cervical length and the risk of preterm delivery. For this reason, if there is an effective intervention for patients with cervix short (about \< 25mm), made this measure in the middle of the second term, the investigators could reduce the prematurity. Regarding possible therapeutic strategies, recent published data demonstrate the effective of vaginal progesterone and cervical pessary in this population. However, both treatments have never been compared and none of the two strategies are indicated in this population. Therefore it results necessary to compare both treatments in order to establish clinical recommendations. The investigators propose a clinical trial to compare two accepted strategies: administration of progesterone (vaginally) or the placement of vaginal pessaries in order to reduce the premature birth (34 weeks and earlier) rate in the population of pregnant women at risk for premature birth, which will be identified by ultrasound during the second trimester of their pregnancy.

Eligibility criteria: Inclusion Criteria:

* Pregnant women with short cervix (=\< 25 mm) identified by use of routine transvaginal ultrasonography at 19-22 weeks of gestation.
* Single pregnancy
* Women older than 18 year-old
* Women sign informed consent according GCP and local legislation
* Gestational age at randomization between 20+1 and 23+6 weeks.

Exclusion Criteria:

* Major fetal abnormalities
* Major uterine abnormalities
* Placenta praevia during current pregnancy
* Vaginal bleeding or ruptured membranes in the moment of randomization
* Cervical cerclage in situ
* History of cone biopsy
* Allergic to peanuts
* Contraindication for Progesterone usage.
* Active treatment with Progesterone at randomization.
* History of 3 or more premature labor.
* If in the investigator's opinion, there are findings on physical examination, abnormalities in the results of clinical analyzes or other medical factors, social or psycho-social that could negatively influence.
* Women unable to give the informed consent

Primary outcomes:
measure: Proportion of spontaneous preterm birth before 34 weeks of gestation
timeFrame: up to 11 weeks (from date of randomization until delivery)
Secondary outcomes:
measure: Proportion of spontaneous preterm birth before 37 weeks of gestation
timeFrame: up to 17 weeks (from date of randomization until delivery)
measure: Proportion of Spontaneous preterm birth before 28 weeks of gestation
timeFrame: up to 8 weeks (from date of randomization until delivery)
measure: Rate of premature rupture of membranes before 34 weeks of gestation
timeFrame: up to 11 weeks (from date of randomization until delivery)
measure: Weight at birth
timeFrame: up to 21 weeks (from date of randomization until delivery)
measure: Rate of fetal and neonatal mortality
timeFrame: From date of randomization until the date of delivery, assessed up 21 weeks
measure: Symptomatic vaginal infections during treatment period
timeFrame: From date of randomization until the date of delivery, assessed up 21 weeks
measure: Proportion of participants with adverse events
timeFrame: From date of randomization until the date of delivery, assessed up 21 weeks
measure: Rate of Chorioamnionitis during third term
timeFrame: From date of randomization until the date of delivery, assessed up 21 weeks
measure: Need of admission because of premature labor before 34 weeks of gestation
timeFrame: up to 14 weeks (from date of randomization until delivery)
measure: Rate of neonatal morbidity
timeFrame: From date of randomization until the date of delivery, assessed up 21 weeks
Other outcomes:
Locations:
city: Sant Joan d'Alacant
country: Spain
facility: University Hospital San Juan de Alicante
state: Alicante
city: Igualada
country: Spain
facility: Igualada Hospital
state: Barcelona
city: Alcalá de Henarés
country: Spain
facility: University Hospital Príncipe de Asturias
state: Madrid
city: Alcorcón
country: Spain
facility: University Hospital Fundación de Alcorcón
state: Madrid
city: Boadilla del Monte
country: Spain
facility: University Hospital Madrid Monte Principe
state: Madrid
city: Fuenlabrada
country: Spain
facility: University Hospital Fuenlabrada
state: Madrid
city: Getafe
country: Spain
facility: University Hospital de Getafe
state: Madrid
city: Leganés
country: Spain
facility: University Hospital Severo Ochoa
state: Madrid
city: Majadahonda
country: Spain
facility: University Hospital Puerta de Hierro
state: Madrid
city: Mostoles
country: Spain
facility: University Hospital Rey Juan Carlos I
state: Madrid
city: Móstoles
country: Spain
facility: University Hospital Mostoles
state: Madrid
city: San Sebastián de los Reyes
country: Spain
facility: Hospital Infanta Sofía
state: Madrid
city: Valdemoro
country: Spain
facility: Hospital Infanta Elena
state: Madrid
city: Gerona
country: Spain
facility: Palamos Hospital
state: Palamos
city: Donostia
country: Spain
facility: Hospital Universitario de Donostia
state: San Sebastian
city: Barcelona
country: Spain
facility: University Hospital Quiron Dexeus
city: Burgos
country: Spain
facility: Burgos University Hospital
city: Ciudad Real
country: Spain
facility: Ciudad Real General University Hospital
city: Guadalajara
country: Spain
facility: Guadalajara General University Hospital
city: León
country: Spain
facility: University Hospital de León
city: Madrid
country: Spain
facility: Sanitas La Zarzuela Hospital
city: Madrid
country: Spain
facility: University Hospital Ramón y Cajal
city: Madrid
country: Spain
facility: Sanitas La Moraleja Hospital
city: Málaga
country: Spain
facility: University Hospital Quirón Málaga
city: Valladolid
country: Spain
facility: Valladolid Clinic Universitary Hospital
city: Valladolid
country: Spain
facility: University Hospital Rio Hortega
city: Zaragoza
country: Spain
facility: University Hospital Miguel Servet
Study officials:
affiliation: University Hospital Puerta de Hierro Majadahonda
name: Sara Cruz Melguizo, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital Puerta de Hierro Majadahonda
name: Cristina Martinez Payo, Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cruz-Melguizo S, San-Frutos L, Martinez-Payo C, Ruiz-Antoran B, Adiego-Burgos B, Campillos-Maza JM, Garcia-Gonzalez C, Martinez-Guisasola J, Perez-Carbajo E, Teulon-Gonzalez M, Avendano-Sola C, Perez-Medina T. Cervical Pessary Compared With Vaginal Progesterone for Preventing Early Preterm Birth: A Randomized Controlled Trial. Obstet Gynecol. 2018 Oct;132(4):907-915. doi: 10.1097/AOG.0000000000002884.
citation: Cabrera-Garcia L, Cruz-Melguizo S, Ruiz-Antoran B, Torres F, Velasco A, Martinez-Payo C, Avendano-Sola C; PESAPRO trial Group. Evaluation of two treatment strategies for the prevention of preterm birth in women identified as at risk by ultrasound (PESAPRO Trial): study protocol for a randomized controlled trial. Trials. 2015 Sep 25;16:427. doi: 10.1186/s13063-015-0964-y.