Cerclage for Twins With Short Cervical Length ≤ 15mm (TWIN-UIC)

Cervical Cerclage for Preventing Spontaneous Preterm Birth in Twin Pregnancies With Transvaginal Ultrasound Cervical Length ≤ 15mm: a Study Protocol for a Randomized Clinical Trial

This is a multicenter randomized study designed to determine if ultrasound indicated cerclage reduces the incidence of spontaneous preterm birth <34 weeks in asymptomatic women with twin gestations and cervical length ≤15mm, diagnosed by transvaginal ultrasound between 16 to 23 6/7 weeks of gestation.

Study Overview

• Status: Recruiting
• Conditions: Preterm Birth; Twin Pregnancy With Antenatal Problem; Short Cervix
• Intervention / Treatment: Procedure: Cervical cerclage

Detailed Description

Twin pregnancies have 59% incidence of preterm delivery (before 37 weeks of gestation), with increased perinatal mortality and neonatal morbidity. No therapy has proven effective in preventing preterm birth in twins. The transvaginal cervical length (TVCL) performed before 24 weeks have been determined to be the best tool to identified women with twin pregnancy at risk of preterm birth (PTB). When short TVCL is identified before 24 weeks, the risk of preterm birth is 60%-70% for TVCL ≤25mm and 80%-90% for TVCL ≤15mm. There are a small number of case reports of cervical cerclage in twin pregnancies with cervical length ≤15mm that suggest decreased preterm birth by 80%. The investigators' objective is to determine if ultrasound indicated cerclage in reduces the incidence of spontaneous preterm birth <34 weeks and improve perinatal outcome in asymptomatic women with twin gestations and cervical length ≤15mm between 16 to 23 6/7 weeks of gestation.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Amanda Roman, MD; Phone Number: 215.955.9200; Email: amanda.roman@jefferson.edu

Study Locations

• Egypt
  • Cairo, Egypt
    • Recruiting
    • The Egyptian IVF Center
    • Contact: Mona Aboulghar, MD; Email: monaaboulghar71@gmail.com
    • Contact: Yahia EL faissal, MD; Email: yahiaelfaissal@gmail.com
• Italy
  • Bologna, Italy
    • Recruiting
    • Bologna University
    • Contact: Giuliana Simonazzi, MD; Email: giuliana.simonazzi@unibo.it
    • Contact: Nicola Rizzo; Email: nicola.rizzo@unibo.it
  • Brescia, Italy
    • Recruiting
    • University of Brescia
    • Contact: Anna Fichera, MD; Email: anna.fichera@gmail.com
    • Contact: Federico Prefumo, MD; Email: federico.prefumo@gmail.com
  • Naples, Italy
    • Recruiting
    • Università degli Studi di Napoli "Federico II"
    • Contact: Gabriele Saccone, MD; Email: gabriele.saccone@libero.it
    • Contact: Pasquale Martinelli, MD; Email: martinel@unina.it
• Spain
  • Barcelona, Spain
    • Recruiting
    • University of Barcelona
    • Contact: Núria Baños, MD; Email: NBANOS@clinic.cat
• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20052
      • Not yet recruiting
      • George Washington University
      • Contact: Alexis Gimovsky, MD; Email: agimovsky@gmail.com
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Thomas Jefferson University Hospital
      • Contact: Amanda Roman, MD; Phone Number: 215-955-9200; Email: amanda.roman@jefferson.edu
  • Texas
    • Austin, Texas, United States, 78758
      • Recruiting
      • Austin Maternal Fetal Medicine St David's Health Care
      • Contact: Sina Haeri, MD
      • Contact: Email: sinahaeri@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 56 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Pregnant women more than 18 years of age (limits the participants to female gender)
2. Diamniotic twin pregnancy
3. Asymptomatic
4. Transvaginal cervical length ≤ 15 mm between 16-23 6/7 weeks gestation

Exclusion Criteria:

1. Singleton or higher order than twins multiple gestation
2. Transvaginal cervical length >15mm
3. Cervical dilation with visible amniotic membranes
4. Amniotic membranes prolapsed into the vagina
5. Fetal reduction after 14 weeks form higher order
6. Monoamniotic twins
7. Twin-twin transfusion syndrome
8. Ruptured membranes
9. Major fetal structural anomaly
10. Fetal chromosomal abnormality
11. Cerclage already in place for other indication
12. Active vaginal bleeding
13. Clinical chorioamnionitis
14. Placenta previa
15. Painful regular uterine contractions
16. Labor

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
Active Comparator: Cervical cerclage + vaginal progesterone; Cervical cerclage in twin pregnancy with transvaginal cervical length ≤15mm and Daily vaginal progesterone 400mg from diagnosis of short cervix to 36 weeks	Procedure: Cervical cerclage; Cervical cerclage indicated by short cervix ≤15mm
No Intervention: Vaginal progesterone; Daily vaginal progesterone 400mg from diagnosis of short cervix to 36 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Preterm delivery less than 34 weeks	Incidence of preterm birth less than 34 weeks (any indication)	at delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Spontaneous preterm birth rates	Incidence of spontaneous preterm birth less than 34 weeks	at delivery
Preterm delivery less than <32 weeks, <28 weeks, or <24 weeks	Incidence of preterm birth less than <32 weeks, <28 weeks, or <24 weeks	at delivery
Mean gestational age at delivery	Mean value of gestational age at delivery (weeks)	at delivery
Birth weight at birth	Mean value (grams)	at delivery
Gestational age at spontaneous rupture of membranes	Mean value (weeks) through study completion	at delivery
Premature rupture of membranes	Incidence	at delivery
Chorioamnionitis	Incidence	at delivery
Composite adverse neonatal outcome	Includes necrotizing enterocolitis, intraventricular hemorrhage (grade 3 or higher), respiratory distress syndrome, bronchopulmonary dysplasia, retinopathy, blood-culture proven sepsis	Incidence between birth and 28 days of age
Neonatal death	Incidence	Between birth and 28 days of age
Maternal death	Incidence	Between birth and 6 weeks postpartum
Interval between diagnosis and delivery	Mean value (days) through study completion	at delivery

Collaborators and Investigators

• Sponsor: Thomas Jefferson University
• Collaborators: Federico II University
• Investigators: Principal Investigator: Amanda Roman, MD, Thomas Jefferson University

Publications and helpful links

General Publications

• Hamilton BE, Hoyert DL, Martin JA, Strobino DM, Guyer B. Annual summary of vital statistics: 2010-2011. Pediatrics. 2013 Mar;131(3):548-58. doi: 10.1542/peds.2012-3769. Epub 2013 Feb 11.
• Goldenberg RL, Iams JD, Miodovnik M, Van Dorsten JP, Thurnau G, Bottoms S, Mercer BM, Meis PJ, Moawad AH, Das A, Caritis SN, McNellis D. The preterm prediction study: risk factors in twin gestations. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Am J Obstet Gynecol. 1996 Oct;175(4 Pt 1):1047-53. doi: 10.1016/s0002-9378(96)80051-2.
• Conde-Agudelo A, Romero R, Hassan SS, Yeo L. Transvaginal sonographic cervical length for the prediction of spontaneous preterm birth in twin pregnancies: a systematic review and metaanalysis. Am J Obstet Gynecol. 2010 Aug;203(2):128.e1-12. doi: 10.1016/j.ajog.2010.02.064. Epub 2010 Jun 23.
• Saccone G, Rust O, Althuisius S, Roman A, Berghella V. Cerclage for short cervix in twin pregnancies: systematic review and meta-analysis of randomized trials using individual patient-level data. Acta Obstet Gynecol Scand. 2015 Apr;94(4):352-8. doi: 10.1111/aogs.12600. Epub 2015 Mar 1.
• Roman A, Rochelson B, Fox NS, Hoffman M, Berghella V, Patel V, Calluzzo I, Saccone G, Fleischer A. Efficacy of ultrasound-indicated cerclage in twin pregnancies. Am J Obstet Gynecol. 2015 Jun;212(6):788.e1-6. doi: 10.1016/j.ajog.2015.01.031. Epub 2015 Jan 28.
• Romero R, Conde-Agudelo A, El-Refaie W, Rode L, Brizot ML, Cetingoz E, Serra V, Da Fonseca E, Abdelhafez MS, Tabor A, Perales A, Hassan SS, Nicolaides KH. Vaginal progesterone decreases preterm birth and neonatal morbidity and mortality in women with a twin gestation and a short cervix: an updated meta-analysis of individual patient data. Ultrasound Obstet Gynecol. 2017 Mar;49(3):303-314. doi: 10.1002/uog.17397.

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2017
• Primary Completion (Anticipated): June 1, 2024
• Study Completion (Anticipated): June 1, 2025

Study Registration Dates

• First Submitted: November 8, 2017
• First Submitted That Met QC Criteria: November 8, 2017
• First Posted (Actual): November 13, 2017

Study Record Updates

• Last Update Posted (Actual): April 27, 2020
• Last Update Submitted That Met QC Criteria: April 23, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth
• Other Study ID Numbers: 17D.326

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)

Drug and device information, study documents

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