TWIN-PEIC: Physical Exam Indicated Cerclage in Twin Gestations

• Sponsor: Thomas Jefferson University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02490384
• Collaborator: Columbia University (Other), Federico II University (Other), Albany Medical College (Other), University of Rochester (Other), George Washington University (Other), Wright State University (Other), Baystate Medical Center (Other), Università degli Studi di Brescia (Other), University of Bologna (Other), University Hospital, Geneva (Other), University of Warsaw (Other), Maternal Fetal Medicine Associates (Other)
• Enrollment: 30
• Locations: 11
• Arms: 2
• Actual Duration (Months): 54.4
• Patients Per Site: 2.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Twin Pregnancy, Antepartum Condition or Complication; Preterm Birth; Cervical Dilation Premature	Procedure: Physical exam indicated cerclage	N/A

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 Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized Control Trial Physical Exam Indicated Cerclage in Twin Gestations
• Actual Study Start Date: Jun 1, 2015
• Actual Primary Completion Date: Dec 1, 2019
• Actual Study Completion Date: Dec 12, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Physical exam indicated cerclage Cerclage	Procedure: Physical exam indicated cerclage; Cervical cerclage
No Intervention: Expectant management No cerclage

Outcome Measures

Primary Outcome Measures

1. Preterm delivery less than 34 weeks [at delivery]

   Incidence of preterm birth less than 34 weeks (any indication)

Secondary Outcome Measures

1. Spontaneous preterm birth less than 34 [at delivery]

   Incidence of spontaneous preterm birth less than 34 weeks

2. Preterm delivery less than <32 weeks, <28 weeks, or <24 weeks [at delivery]

   Incidence of preterm birth less than <32 weeks, <28 weeks, or <24 weeks

3. Mean gestational age at delivery [at delivery]

   Mean value of gestational age at delivery (weeks)

4. Birth weight at birth [at delivery]

   Mean value (grams)

5. Gestational age at spontaneous rupture of membranes [at presentation of rupture membranes]

   Mean value (weeks) through study completion

Other Outcome Measures

1. Chorioamnionitis [Time of delivery]

   Incidence

2. Composite adverse neonatal outcome [Incidence between birth and 28 days of age]

   Includes necrotizing enterocolitis, intraventricular hemorrhage (grade 3 or higher), respiratory distress syndrome, bronchopulmonary dysplasia, retinopathy, blood-culture proven sepsis

3. Fetal demise [Incidence before delivery]

   Incidence

4. Neonatal death [Incidence between birth and 28 days of age]

   Incidence

5. Perinatal death [Incidence before and after birth ulntil 28 days of age]

   Incidence

6. Maternal death [Between birth and 6 weeks postpartum]

   Incidence

7. Interval between diagnosis and delivery [at delivery]

   Mean value (days) through study completion

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	George Washington University	Washington	District of Columbia	United States	20037
2	Albany Medical Center	Albany	New York	United States	12208
3	Columbia University Medical Center	New York	New York	United States	10032
4	University of Rochester Medical Center	Rochester	New York	United States	14642
5	Wright State University	Dayton	Ohio	United States	45409
6	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania	United States	19107
7	Austin Maternal Fetal Medicine St David's Health Care	Austin	Texas	United States	78758
8	Bologna University	Bologna		Italy
9	University of Brescia	Brescia		Italy
10	Università degli Studi di Napoli "Federico II"	Naples		Italy
11	University of Warsaw	Warsaw		Poland

Sponsors and Collaborators

• Thomas Jefferson University
• Columbia University
• Federico II University
• Albany Medical College
• University of Rochester
• George Washington University
• Wright State University
• Baystate Medical Center
• Università degli Studi di Brescia
• University of Bologna
• University Hospital, Geneva
• University of Warsaw
• Maternal Fetal Medicine Associates

Investigators

• Principal Investigator: Amanda Roman, MD, [e-mail]

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 20, 2015
• Informed Consent Form - May 8, 2015

More Information

Publications

• 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.
• 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.
• 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. Review.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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. Review.
• 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.
• 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. Review.
• 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, Cetingöz 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.
• 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.

• Responsible Party: Thomas Jefferson University
• ClinicalTrials.gov Identifier: NCT02490384
• Other Study ID Numbers: ThomasJeffersonU
• First Posted: Jul 3, 2015
• Last Update Posted: Apr 27, 2020
• Last Verified: Apr 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Thomas Jefferson University: Cervical cerclage
• Additional relevant MeSH terms: Premature Birth

Study Results

No Results Posted as of Apr 27, 2020