The Trial of Pessary After Laser for TTTS (PECEPLASER)

Arabin Cervical Pessary for Prevention of Preterm Birth in Cases of Twin-to-twin Transfusion Syndrome Treated by Fetoscopic Laser Coagulation: The PECEP Laser Trial

Placing a cervical pessary in severe twin-to-twin transfusion syndrome (TTTS) cases treated by fetoscopic laser coagulation (FLC) decreases the spontaneous preterm birth rate.

Study Overview

• Status: Terminated
• Conditions: Premature Birth
• Intervention / Treatment: Device: Arabin Cervical Pessary

Detailed Description

Monochorionic (MC) twin pregnancies present with a high rate of fetal complications, most of them associated with the placental vascular anastomoses. Fetoscopic laser coagulation (FLC) is a surgical technique that allows minimally invasive access into the uterus and has emerged as a useful tool in the management of the most common and severe of these complications, twin to twin transfusion syndrome (TTTS). Even though, preterm birth remains a common cause of adverse outcome because TTTS is associated with a 29% risk of delivering before 28 weeks.

A short cervical length (CL), defined as a CL ≤ 25 mm, detected by transvaginal ultrasound is an independent risk factor for preterm birth in twin pregnancies but no effective treatment has been described to prevent it.

Although is usually accepted that in twin pregnancies cerclage may increase the risk of preterm birth, Salomon and co-workers, found that in cases of TTTS with a CL below the 5th percentile (15 mm) at the time of surgery, performing an emergency cerclage prolonged the pregnancy and allow for better outcome, But still preterm birth after FLC remains a big challenge, so new methods to prevent it must be investigated.

Previous studies in singletons and twins have shown that the use of cervical pessary significantly reduces the frequency of birth before 32 weeks and prolongs pregnancy. The advantage of using cervical pessary is that it is less invasive than cerclage and can be removed easily. That's the reason why pessaries could be considered an alternative, non invasive option to prevent preterm birth in cases of twin to twin transfusion syndrome (TTTS) treated by laser surgery.

• Study Type: Interventional
• Enrollment (Actual): 352
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • UZ Leuven. Campus Gasthuisberg
• Germany
  • Frankfurt, Germany, 60318
    • Frauenklinik - Zentrum für Ultraschalldiagnostik und Pränatalmedizin Bürgerhospital und Clementine Kinderhospital gemeinnützige GmbH
  • Hamburg, Germany, 20246
    • University Medical Center Eppendorf
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Monochorionic twin pregnancies with severe TTTS requiring intrauterine surgery
• Less than 26 weeks
• Minimal age of 18 years
• Informed consent signature

Exclusion Criteria:

• Major fetal abnormalities (requiring surgery or leading to infant death or severe handicap)
• Cerclage prior to randomisation
• Uterine malformation
• Placenta previa
• Active vaginal bleeding at the moment of randomization
• Spontaneous rupture of membranes at the time of randomization
• Death of both twins after the surgery
• Monochorionic-monoamniotic twin pregnancy
• Silicone allergy
• Current participation in other RCT

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Usual management; Usual management of monochorionic pregnancy without the pessary placement
Other: Arabin Cervical Pessary; The pessary will be inserted 24 hours after fetal surgery in the exploration room. This procedure does not need anaesthesia and it does not need to be done in a surgery room. During the following explorations the correct placement of the pessary is assessed, and if it does not, it can be easily adjusted. The pessary will be removed at 37 weeks of gestation, or before if any unexpected event occurs.	Device: Arabin Cervical Pessary; The Arabin cervical pessary, which is CE-certified for preventing SPB (CE 0482 / EN ISO 13485: 2003 annex III of the council directive 93/42 EEC). It is a vaginal device which is used to treat pregnant women for preventing spontaneous preterm birth. This device can be easily placed around the uterine cervix without pain.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delivery before 32 weeks	Rate of delivery before 32 weeks	Within the first 15 days after delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Birth weight	Median weight (g) of the newborns at birth.	Within the first 15 days after delivery
Fetal or neonatal death	Rate of intrauterine demise or neonatal death during the first 24 hours.	Within the first 15 days after the death
Neonatal morbidity	Rate of major adverse neonatal outcomes before discharge from the hospital.	30 days after the discharge from the hospital
Significant maternal adverse events	Rate of heavy bleeding (bleeding that requires a medical intervention), cervical tear (cervical rupture due to the pessary placement), and/or uterine rupture (rupture of the uterus due to contractions or surgery).	Within 15 days after discharge from the hospital
Physical or psychological intolerance to pessary	Discomfort or pain due to the pessary that makes daily life uncomfortable (number of cases).	Within 15 days after discharge from hospital
Preterm birth before 37 weeks	Rate of delivery before 36+6 weeks	Within 15 days after delivery
Rupture of membranes before 32 weeks	Rupture of amniotic membranes before 31+6 weeks	Within 15 days after delivery
Hospitalisation for threatened preterm labour before 32 weeks	Requirement of hospitalisation due to preterm contractions that need medical treatment to try to stop them before 31+6 weeks (rate).	Within 15 days after delivery
Time to birth		Within 15 days after delivery
Preterm birth before 34 weeks	rate of delivery before 33+6 weeks	Within 15 days after delivery
Preterm birth before 30 weeks	rate of delivery before 29+6 weeks	Within 15 days after delivery
Preterm birth before 28 weeks	rate of delivery before 27+6 weeks	Within 15 days after delivery

Collaborators and Investigators

• Sponsor: Hospital Universitari Vall d'Hebron Research Institute
• Collaborators: Universitaire Ziekenhuizen KU Leuven; Universitätsklinikum Hamburg-Eppendorf; Maternal-Infantil Vall d´Hebron Hospital; Bürgerhospital Frankfurt
• Investigators: Principal Investigator: Elena Carreras, PhD, Hospital Vall d'Hebron

Publications and helpful links

General Publications

• Goya M, Pratcorona L, Merced C, Rodo C, Valle L, Romero A, Juan M, Rodriguez A, Munoz B, Santacruz B, Bello-Munoz JC, Llurba E, Higueras T, Cabero L, Carreras E; Pesario Cervical para Evitar Prematuridad (PECEP) Trial Group. Cervical pessary in pregnant women with a short cervix (PECEP): an open-label randomised controlled trial. Lancet. 2012 May 12;379(9828):1800-6. doi: 10.1016/S0140-6736(12)60030-0. Epub 2012 Apr 3. Erratum In: Lancet. 2012 May 12;379(9828):1790.
• Liem S, Schuit E, Hegeman M, Bais J, de Boer K, Bloemenkamp K, Brons J, Duvekot H, Bijvank BN, Franssen M, Gaugler I, de Graaf I, Oudijk M, Papatsonis D, Pernet P, Porath M, Scheepers L, Sikkema M, Sporken J, Visser H, van Wijngaarden W, Woiski M, van Pampus M, Mol BW, Bekedam D. Cervical pessaries for prevention of preterm birth in women with a multiple pregnancy (ProTWIN): a multicentre, open-label randomised controlled trial. Lancet. 2013 Oct 19;382(9901):1341-9. doi: 10.1016/S0140-6736(13)61408-7. Epub 2013 Aug 5.
• Carreras E, Arevalo S, Bello-Munoz JC, Goya M, Rodo C, Sanchez-Duran MA, Peiro JL, Cabero L. Arabin cervical pessary to prevent preterm birth in severe twin-to-twin transfusion syndrome treated by laser surgery. Prenat Diagn. 2012 Dec;32(12):1181-5. doi: 10.1002/pd.3982. Epub 2012 Oct 11.
• Goya M, Pratcorona L, Higueras T, Perez-Hoyos S, Carreras E, Cabero L. Sonographic cervical length measurement in pregnant women with a cervical pessary. Ultrasound Obstet Gynecol. 2011 Aug;38(2):205-9. doi: 10.1002/uog.8960. Epub 2011 Jul 18.
• Rodo C, Arevalo S, Lewi L, Couck I, Hollwitz B, Hecher K, Carreras E. Arabin cervical pessary for prevention of preterm birth in cases of twin-to-twin transfusion syndrome treated by fetoscopic LASER coagulation: the PECEP LASER randomised controlled trial. BMC Pregnancy Childbirth. 2017 Aug 1;17(1):256. doi: 10.1186/s12884-017-1435-0.

Helpful Links

• Arabin Cervical Pessary

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2012
• Primary Completion (Actual): January 1, 2020
• Study Completion (Actual): June 25, 2020

Study Registration Dates

• First Submitted: April 12, 2011
• First Submitted That Met QC Criteria: April 12, 2011
• First Posted (Estimate): April 13, 2011

Study Record Updates

• Last Update Posted (Actual): August 27, 2020
• Last Update Submitted That Met QC Criteria: August 25, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Cervical length; Cervical pessary; Twin to twin transfusion syndrome; Monochorionic pregnancy
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth
• Other Study ID Numbers: PECEP_LASER Trial

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No