Pessary to Prevent Prematurity in Twins in Case of Short Cervix (PESSAR'ONE)

For 25 years, the twin pregnancy rate has regularly increased in the majority of European countries and in the United States, by 35% between 1981 and 2006. Increased use of medically assisted procreation and older maternal age are the two main causes. At the present time twin pregnancies represent nearly 20% of premature deliveries. The rate of very premature births (< 32-34 weeks) is 7 times higher in twin pregnancies than in singleton pregnancies. As prematurity accounts for 75% of neonatal morbidity and mortality, and extreme prematurity is the principal cause of neonatal mortality and of brain sequelae in twins, the search for a preventive treatment appears as a priority in perinatal medicine. The investigators recently showed in a prospective multicenter study that cervical ultrasound at 22 and 27 wks was a better predictive investigation of premature delivery < 34 wks than digital examination. Recently in a randomized trial in a population of short-cervix singleton pregnancies, the premature delivery rate decreased by 40% in the pessary group compared with the usual management group. No other trial of pessary use in short-cervix twin pregnancies was published today. Recently, in a historical comparison of twins with twin-to-twin transfusion syndrome treated with laser, Carreras et al. have showed a decreased rate of preterm delivery with the use of pessary in case of short cervix. The investigators wish to set up a randomized multicenter study in France in the population of short-cervix twin pregnancies to show a potential benefit of the pessary compared with simple surveillance.

Study Overview

• Status: Completed
• Conditions: Pregnancy
• Intervention / Treatment: Device: Pessary

Detailed Description

For 25 years, the twin pregnancy rate has regularly increased in the majority of European countries and in the United States, by 35% between 1981 and 2006. Increased use of medically assisted procreation and older maternal age are the two main causes. At the present time twin pregnancies represent nearly 20% of premature deliveries. The rate of very premature births (< 32-34 weeks) is 7 times higher in twin pregnancies than in singleton pregnancies. As prematurity accounts for 75% of neonatal morbidity and mortality, and extreme prematurity is the principal cause of neonatal mortality and of brain sequelae in twins, the search for a preventive treatment appears as a priority in perinatal medicine. The investigators recently showed in a prospective multicenter study that cervical ultrasound at 22 and 27 wks was a better predictive investigation of premature delivery < 34 wks than digital examination.[1] As there is currently no recommended preventive treatment for prematurity in twin pregnancies[2], the 2009 guidelines of the College of Obstetricians leave the teams with the option of carrying out systematic cervical ultrasound or not during follow-up investigations.[3] Recently in a randomized trial in a population of short-cervix singleton pregnancies, the premature delivery rate decreased by 40% in the pessary group compared with the usual management group.[4] In a recent multicenter trial (ProTWIN), while therapeutic efficacy of the pessary (versus usual management) was not demonstrated in the overall group of twin pregnancies, in the short-cervix subgroup (< 25th percentile of the population) the < 32 wks delivery rate decreased from 29% to 14% (OR= 0.49 (0.24-0.97) and neonatal morbidity also decreased.[5] No other trial of pessary use in short-cervix twin pregnancies was published today. Recently, in a historical comparison of twins with twin-to-twin transfusion syndrome treated with laser, Carreras et al. have showed a decreased rate of preterm delivery with the use of pessary in case of short cervix.[6] The investigators wish to set up a randomized multicenter study in France in the population of short-cervix twin pregnancies to show a potential benefit of the pessary compared with simple surveillance.

• Study Type: Interventional
• Enrollment (Actual): 324
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Angers, France
    • CHU Angers
  • Bordeaux, France
    • CHU Bordeaux
  • Caen, France
    • CHU caen
  • Lille, France
    • CHRU Lille
  • Marseille, France
    • Hôpital Saint-Joseph
  • Marseille, France
    • Hôpital Marseille AP-HM
  • Nantes, France
    • CHU Nantes
  • Paris, France
    • Hôpital Robert Debré
  • Paris, France
    • Hôpital Necker
  • Paris, France
    • Hôpital Bicêtre
  • Paris, France
    • GH Pitié Salpêtrière
  • Paris, France
    • Hôpital Antoine Béclère
  • Paris, France
    • Maternité Port-Royal Cochin
  • Poissy, France
    • CHI Poissy
  • Saint-Etienne, France
    • CHU Saint-etienne
  • Strasbourg, France
    • Hôpital Universitaire de Strasbourg
  • Toulouse, France, 31059
    • CHU Toulouse
  • Tours, France
    • Chu Tours

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

Asymptomatic twin pregnancies between 16 and 24+0 weeks CL < 25th percentile for GA

- < 35mm between 16 and 24+0d weeks Vaginal swabs for bacteriological analysis < 72 hours Patient age > 18 years Written informed consent obtained French first language (speak, read, understand) French social security cover

Exclusion Criteria:

• Painful regular contractions
• Major fetal abnormalities
• Fetal malformation
• Active vaginal bleeding, placenta praevia
• Discordance fetal weight more than 40%
• Treatment with progesterone
• Patient with cerclage
• Ruptured of membrane
• Twin to twin transfusion syndrome
• Uterine malformation
• Chronic maternal disease (diabetes, hypertension, renal insufficiency, Heparin Treatment)
• Conisation history
• patients subject to a judicial safeguard order, participating in another research study including an exclusion period which has not expired at the time of screening will not be included

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pessary; The device will be placed in the vagina during the consultation. It is rinsed in sterile water for lubrification and left in place until delivery or remove at 36 weeks in case of no delivery before. There is no need to use any analgesia. The good position of the pessary is checking in the same time than the placement with digital examination.	Device: Pessary; The device will be placed in the vagina during the consultation. It is rinsed in sterile water for lubrification and left in place until delivery or remove at 36 weeks in case of no delivery before. There is no need to use any analgesia. The good position of the pessary is checking in the same time than the placement with digital examination.
No Intervention: No pessary; No pessary will be placed in the vagina.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
perinatal death or significant neonatal morbidity until discharge from the hospital	it's a composite outcome : perinatal death (i.e medical interruption of pregnancy, intrauterine fetal death, or death occurring during the first four weeks after birth, before day 29), or significant neonatal morbidity until discharge from the hospital, defined as one or more of the following complications: bronchopulmonary dysplasia (BPD), intraventricular haemorrhage (IVH) grade III or IV, periventricular leucomalacia (PVL), necrotizing enterocolitis (NEC) grade II or higher, culture proven sepsis, retinopathy of prematurity (ROP) requiring treatment.	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Preterm delivery	6 months
To evaluate the prolongation of pregnancy in days	6 months
The differential cost-efficacy ratio of the two strategies	6 months
Tolerance of the pessary	6 months

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Investigators: Study Director: Christophe Vayssière, PhD, CHU Toulouse

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Actual): October 1, 2018
• Study Completion (Actual): October 1, 2018

Study Registration Dates

• First Submitted: October 1, 2014
• First Submitted That Met QC Criteria: December 29, 2014
• First Posted (Estimate): December 31, 2014

Study Record Updates

• Last Update Posted (Actual): July 30, 2020
• Last Update Submitted That Met QC Criteria: July 28, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: prematurity; short cervix; twin pregnancy; pessary
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth
• Other Study ID Numbers: 13 7048 01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No