Physical Exam Indicated Cerclage in Twin Gestations (TWIN-PEIC)

Randomized Control Trial Physical Exam Indicated Cerclage in Twin Gestations

This is a multicenter randomized study designed to determine if physical exam indicated cerclage reduces the incidence of spontaneous preterm birth <34 weeks in asymptomatic women with twin gestations and dilated cervix, diagnosed by pelvic exam between 16 to 23 6/7 weeks of gestation.

Study Overview

• Status: Terminated
• Conditions: Preterm Birth; Twin Pregnancy, Antepartum Condition or Complication; Cervical Dilation Premature
• Intervention / Treatment: Procedure: Physical exam indicated cerclage

Detailed Description

Twin pregnancies have 58% 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. When cervical dilation is identified before 24 weeks in singleton pregnancies, the risk of preterm birth is 90%-100%; based on a small series of cases, approximately 50% of twin gestations with cervical dilation will be delivered prior to viability (24 weeks) and the risk of preterm birth prior to 34 and 37 weeks was 85% and 100%. Cervical dilation is the worst prognostic factor for preterm birth. There are a small number of case reports of cervical cerclage in twin pregnancies with a dilated cervix that suggest similar outcomes to those in singleton pregnancies. The investigators' objective is to determine if physical exam indicated cerclage reduces the incidence of spontaneous preterm birth <34 weeks and improve perinatal outcome in asymptomatic women with twin gestations and dilated cervix (1 to 5 cm) between 16 to 23 6/7 weeks of gestation.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Bologna, Italy
    • Bologna University
  • Brescia, Italy
    • University of Brescia
  • Naples, Italy
    • Università degli Studi di Napoli "Federico II"
• Poland
  • Warsaw, Poland
    • University of Warsaw
• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • George Washington University
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical Center
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
  • Ohio
    • Dayton, Ohio, United States, 45409
      • Wright State University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
  • Texas
    • Austin, Texas, United States, 78758
      • Austin Maternal Fetal Medicine St David's Health Care

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:

1. Pregnant women older than 18 years of age
2. Diamniotic twin pregnancy
3. Cervical dilation between 1 to 5 cm and/or visible membranes by pelvic exam or speculum exam between at 16-23 6/7 weeks gestation

Exclusion Criteria:

1. Singleton pregnancy or higher order than twins multiple gestation
2. Cervical dilation more than 5 cm
3. Amniotic membranes prolapsed beyond external os into the vagina, unable to visualize cervical tissue
4. More than 24 weeks of gestation
5. Multifetal reduction after 14 weeks
6. Monoamniotic twins
7. Twin-twin transfusion syndrome
8. Ruptured amniotic membranes at the time of diagnosis of dilated cervix
9. Major fetal structural anomaly
10. Fetal chromosomal abnormality
11. Cerclage already in place for other indications
12. Active vaginal bleeding
13. Suspicion of clinical or biochemical chorioamnionitis
14. Painful regular uterine contractions
15. Labor (progressing cervical dilation)
16. Placenta previa

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: Physical exam indicated cerclage; Cerclage	Procedure: Physical exam indicated cerclage; Cervical cerclage
No Intervention: Expectant management; No cerclage

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
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
Spontaneous preterm birth less than 34	Incidence of spontaneous preterm birth less than 34 weeks	at delivery
Gestational age at spontaneous rupture of membranes	Mean value (weeks) through study completion	at presentation of rupture membranes

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Maternal death	Incidence	Between birth and 6 weeks postpartum
Interval between diagnosis and delivery	Mean value (days) through study completion	at delivery
Chorioamnionitis	Incidence	Time of delivery
Fetal demise	Incidence	Incidence before delivery
Neonatal death	Incidence	Incidence between birth and 28 days of age
Perinatal death	Incidence	Incidence before and after birth ulntil 28 days of age

Collaborators and Investigators

• Sponsor: Thomas Jefferson University
• Collaborators: University Hospital, Geneva; University of Bologna; Columbia University; Federico II University; George Washington University; University of Rochester; Baystate Medical Center; Albany Medical College; Wright State University; Università degli Studi di Brescia; Maternal Fetal Medicine Associates; University of Warsaw
• Investigators: Principal Investigator: Amanda Roman, MD, amanda.roman@jefferson.edu

Publications and helpful links

General Publications

• Romero R, Nicolaides K, Conde-Agudelo A, Tabor A, O'Brien JM, Cetingoz E, Da Fonseca E, Creasy GW, Klein K, Rode L, Soma-Pillay P, Fusey S, Cam C, Alfirevic Z, Hassan SS. Vaginal progesterone in women with an asymptomatic sonographic short cervix in the midtrimester decreases preterm delivery and neonatal morbidity: a systematic review and metaanalysis of individual patient data. Am J Obstet Gynecol. 2012 Feb;206(2):124.e1-19. doi: 10.1016/j.ajog.2011.12.003. Epub 2011 Dec 11.
• 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.
• 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.
• 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.
• Rouse DJ, Caritis SN, Peaceman AM, Sciscione A, Thom EA, Spong CY, Varner M, Malone F, Iams JD, Mercer BM, Thorp J, Sorokin Y, Carpenter M, Lo J, Ramin S, Harper M, Anderson G; National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. A trial of 17 alpha-hydroxyprogesterone caproate to prevent prematurity in twins. N Engl J Med. 2007 Aug 2;357(5):454-61. doi: 10.1056/NEJMoa070641.
• Schuit E, Stock S, Groenwold RH, Maurel K, Combs CA, Garite T, Spong CY, Thom EA, Rouse DJ, Caritis SN, Saade GR, Zachary JM, Norman JE, Rode L, Klein K, Tabor A, Cetingoz E, Morrison JC, Magann EF, Briery CM, Serra V, Perales A, Meseguer J, Nassar AH, Lim AC, Moons KG, Kwee A, Mol BW. Progestogens to prevent preterm birth in twin pregnancies: an individual participant data meta-analysis of randomized trials. BMC Pregnancy Childbirth. 2012 Mar 15;12:13. doi: 10.1186/1471-2393-12-13.
• 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.
• Rebarber A, Bender S, Silverstein M, Saltzman DH, Klauser CK, Fox NS. Outcomes of emergency or physical examination-indicated cerclage in twin pregnancies compared to singleton pregnancies. Eur J Obstet Gynecol Reprod Biol. 2014 Feb;173:43-7. doi: 10.1016/j.ejogrb.2013.11.016. Epub 2013 Nov 28.
• Gupta M, Emary K, Impey L. Emergency cervical cerclage: predictors of success. J Matern Fetal Neonatal Med. 2010 Jul;23(7):670-4. doi: 10.3109/14767050903387011.
• Zanardini C, Pagani G, Fichera A, Prefumo F, Frusca T. Cervical cerclage in twin pregnancies. Arch Gynecol Obstet. 2013 Aug;288(2):267-71. doi: 10.1007/s00404-013-2758-3. Epub 2013 Feb 21.
• Miller ES, Rajan PV, Grobman WA. Outcomes after physical examination-indicated cerclage in twin gestations. Am J Obstet Gynecol. 2014 Jul;211(1):46.e1-5. doi: 10.1016/j.ajog.2014.03.034. Epub 2014 Mar 18.
• Berghella V, Roman A. Cerclage in twins: we can do better! Am J Obstet Gynecol. 2014 Jul;211(1):5-6. doi: 10.1016/j.ajog.2014.03.037. No abstract available.
• Althuisius SM, Dekker GA, Hummel P, van Geijn HP; Cervical incompetence prevention randomized cerclage trial. Cervical incompetence prevention randomized cerclage trial: emergency cerclage with bed rest versus bed rest alone. Am J Obstet Gynecol. 2003 Oct;189(4):907-10. doi: 10.1067/s0002-9378(03)00718-x.
• Roman A, Rochelson B, Martinelli P, Saccone G, Harris K, Zork N, Spiel M, O'Brien K, Calluzzo I, Palomares K, Rosen T, Berghella V, Fleischer A. Cerclage in twin pregnancy with dilated cervix between 16 to 24 weeks of gestation: retrospective cohort study. Am J Obstet Gynecol. 2016 Jul;215(1):98.e1-98.e11. doi: 10.1016/j.ajog.2016.01.172. Epub 2016 Jan 28.
• Roman A, Zork N, Haeri S, Schoen CN, Saccone G, Colihan S, Zelig C, Gimovsky AC, Seligman NS, Zullo F, Berghella V. Physical examination-indicated cerclage in twin pregnancy: a randomized controlled trial. Am J Obstet Gynecol. 2020 Dec;223(6):902.e1-902.e11. doi: 10.1016/j.ajog.2020.06.047. Epub 2020 Jun 25.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2015
• Primary Completion (Actual): December 1, 2019
• Study Completion (Actual): December 12, 2019

Study Registration Dates

• First Submitted: June 29, 2015
• First Submitted That Met QC Criteria: July 1, 2015
• First Posted (Estimate): July 3, 2015

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

• Keywords: Cervical cerclage
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth
• Other Study ID Numbers: ThomasJeffersonU

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De identified data
• IPD Sharing Time Frame: June 2020 2 years
• IPD Sharing Access Criteria: x
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR