Cervical Occlusion Double-level Stitch Application (COSA)

Comparison of the Efficacy of Emergency Double-level and Single Cervical Cerclage in Cervical Insufficiency in the Second Trimester of Pregnancy - Multicenter Prospective Randomized Trial

Cervical insufficiency is defined as painless dilatation of the cervix during the second trimester of pregnancy. As a result of shortening and opening of the cervix, despite the lack of uterine contractions, the fetal membranes invade into the cervical canal and then into the vagina, which results in premature rupture of the membranes and miscarriage or preterm delivery. Cervical insufficiency occurs in approximately 1% of the women. The aim of the study is to evaluate the effectiveness of placing a double-level cervical cerclage in the treatment of advanced cervical insufficiency. The hypothesis assumes that the insertion of a double-level suture is associated with a reduction in the rate of deliveries < 34 weeks of gestation in comparison to single-level suture. The study will include women with fetal membranes visible through open external os of the cervix between 16+0 and 25+6 weeks. They will be randomized to two arms - McDonald's single cervical cerclage or two-level cerclage.

Study Overview

• Status: Completed
• Conditions: Cervical Incompetence
• Intervention / Treatment: Procedure: Double-level cervical cerclage; Procedure: Single-level cervical cerclage

Detailed Description

This is an open-label, multicentre, prospective, randomised controlled trial (RCT). Women will be randomized to the single-level cerclage arm or the double-level cerclage. Each patient will have a vaginal swab for aerobic and anaerobic bacteria and fungi culture, as well as for mycoplasmas, chlamydia and ureaplasma performed. Each patient will be treated with progesterone (vaginally 2 x 100 mg per day) and empirical antibiotic therapy (ceftriaxone 2.0 g iv + clarithromycin 2 x 500 mg po + metronidazole 3 x 500 mg iv for 7 days). If specific pathogens will be detected, the antibiotic therapy will be modified according to the antibiogram. If the diagnosis of cervical insufficiency will be made >23 weeks of gestation a single course of corticosteroid therapy will be administered (betamethasone 2 x 12 mg im) if the rsik of delivery within 7 days will be assessed as high. Indomethacin will also be administered for 48 hours (starting the day of cerclage administration, indomethacin 2 x 75 mg po for 48 hours). In the single-level cerclage arm McDonald suture will be administered. In the double-level cerclage arm two separate sutures analogous to McDonald technique will be placed, one approximately 1 cm higher above the other. Patients will be followed up until miscarriage or delivery and will receive standard perinatal care. Gestational age at delivery, the occurrence of cerclage complications and neonatal outcomes will be analyzed.

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Poland
  • Warsaw, Poland
    • Institute of Mother and Child
  • Kuyavian-Pomeranian Voivodeship
    • Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland, 85-168
      • Department of Obstetrics, Women's Diseases and Oncological Gynecology, Nicolaus Copernicus University
  • Masovian Voivodeship
    • Warsaw, Masovian Voivodeship, Poland, 01-004
      • 1st Department of Obstetrics and Gynecology, Center of Postagraduate Medical Education
    • Warsaw, Masovian Voivodeship, Poland, 01-809
      • Department of Obstetrics, Perinatology and Neonatology, Center of Postagraduate Medical Education
    • Warsaw, Masovian Voivodeship, Poland, 02-015
      • 1st Department of Obstetrics and Gynecology, Medical University of Warsaw
  • Pomeranian Voivodeship
    • Gdansk, Pomeranian Voivodeship, Poland, 80-952
      • Department of Obstetrics and Gynecology, Oncological Gynecology and Gynecological Endocrinology, Medical University of Gdansk
  • Łódź Voivodeship
    • Lodz, Łódź Voivodeship, Poland, 93-338
      • Polish Mother's Memorial Hospital - Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 46 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• singleton pregnancy,
• gestational age 16+0 to 25+6 weeks,
• live fetus,
• cervical incompetence with fetal membranes visible through external os before 24+0 weeks of gestation,
• informed written consent.

Exclusion Criteria - any of the following occuring before the administration of the cerclage:

• preterm premature rupture of membranes,
• vaginal bleeding,
• active regular uterine contractions,
• fetal demise,
• fever,
• intrauterine infection (diagnosed in case of maternal body temperature ≥ 38°C with no alternative cause identified and at least 2 symptoms among the following appear: fetal tachycardia > 160 bpm for 10 minutes or longer, uterine pain, purulent vaginal discharge, white blood cell count > 15 G/L in the absence of corticosteroid treatment or increased plasma C-reactive protein > 10 mg/L),
• known genetic defects of the fetus,
• known lethal fetal malformations,
• congenital uterine defects,
• multiple pregnancy.

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: Double-level cerclage; double-level cervical cerclage placement with one suture above the other approximately 1 cm higher. Suture will be placed analogous to McDonald technique	Procedure: Double-level cervical cerclage; two cervical sutures + regimen of antibiotics + indomethacin + progesterone
Active Comparator: Single-level cerclage; single-level cervical cerclage of McDonald technique	Procedure: Single-level cervical cerclage; single cervical suture + regimen of antibiotics + indomethacin + progesterone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
deliveries below 34+0 weeks of gestation	number and rate of deliveries below 34+0 weeks of gestation	observation after intervention for 26 weeks of until birth

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
gestational age at delivery	duration of pregnancy untill delivery in weeks and days	observation after intervention for 26 weeks of until birth
time from cerclage administration to delivery	time from cerclage administration to delivery in days	observation after intervention for 26 weeks of until birth
fetal demise	number and rate of pregnancies complicated by fetal demise	observation after intervention for 26 weeks of until birth
neonatal outcomes	number and rate of: congenital infections, respiratory morbidity, hospitalizations in the Neonatal Intensive Care Unit, early neurodevelopmental morbidity, gastrointestinal morbidity, retinopathy of prematurity, newborn's death before the discharge home	observation after intervention for 26 weeks of until birth
birth weight	neonatal weight at delivery in grams	observation after intervention for 26 weeks of until birth
5th minute Apgar score	neonatal general condition at 5th minute after delivery according to the Apgar Scale	observation after intervention for 26 weeks of until birth
maternal outcomes	maternal mortality, miscarriage, intrauterine infection, prelabour rupture of membranes, o cervical laceration	observation after intervention for 26 weeks of until birth

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
cerclage procedure complications occurring within 48 hours after cerclage placement	excessive vaginal bleeding, intrauterine infection, prelabour rupture of membranes	observation after intervention for 48 hours

Collaborators and Investigators

• Sponsor: Centre of Postgraduate Medical Education
• Collaborators: Medical University of Warsaw; Polish Mother Memorial Hospital Research Institute; Medical University of Gdansk; Institute of Mother and Child, Warsaw, Poland; Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz
• Investigators: Principal Investigator: Katarzyna Kosinska Kaczynska, Prof., Center of Postgraduate Medical Education; Principal Investigator: Anna Kajdy, MD PhD, Center of Postgraduate Medical Education; Principal Investigator: Mariusz Grzesiak, Prof., Polish Mother's Memorial Hospital - Research Institute

Publications and helpful links

General 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. doi: 10.1067/s0002-9378(03)00718-x.
• Daskalakis G, Papantoniou N, Mesogitis S, Antsaklis A. Management of cervical insufficiency and bulging fetal membranes. Obstet Gynecol. 2006 Feb;107(2 Pt 1):221-6. doi: 10.1097/01.AOG.0000187896.04535.e6.
• Stupin JH, David M, Siedentopf JP, Dudenhausen JW. Emergency cerclage versus bed rest for amniotic sac prolapse before 27 gestational weeks. A retrospective, comparative study of 161 women. Eur J Obstet Gynecol Reprod Biol. 2008 Jul;139(1):32-7. doi: 10.1016/j.ejogrb.2007.11.009. Epub 2008 Feb 20.
• Oh KJ, Romero R, Park JY, Lee J, Conde-Agudelo A, Hong JS, Yoon BH. Evidence that antibiotic administration is effective in the treatment of a subset of patients with intra-amniotic infection/inflammation presenting with cervical insufficiency. Am J Obstet Gynecol. 2019 Aug;221(2):140.e1-140.e18. doi: 10.1016/j.ajog.2019.03.017. Epub 2019 Mar 28.
• Miller ES, Grobman WA, Fonseca L, Robinson BK. Indomethacin and antibiotics in examination-indicated cerclage: a randomized controlled trial. Obstet Gynecol. 2014 Jun;123(6):1311-1316. doi: 10.1097/AOG.0000000000000228.
• Wood SL, Owen J. Cerclage: Shirodkar, McDonald, and Modifications. Clin Obstet Gynecol. 2016 Jun;59(2):302-10. doi: 10.1097/GRF.0000000000000190.
• Park JM, Tuuli MG, Wong M, Carbone JF, Ismail M, Macones GA, Odibo AO. Cervical cerclage: one stitch or two? Am J Perinatol. 2012 Jun;29(6):477-81. doi: 10.1055/s-0032-1304831. Epub 2012 Mar 7.
• Giraldo-Isaza MA, Fried GP, Hegarty SE, Suescum-Diaz MA, Cohen AW, Berghella V. Comparison of 2 stitches vs 1 stitch for transvaginal cervical cerclage for preterm birth prevention. Am J Obstet Gynecol. 2013 Mar;208(3):209.e1-9. doi: 10.1016/j.ajog.2012.11.039. Epub 2012 Nov 28.
• Woensdregt K, Norwitz ER, Cackovic M, Paidas MJ, Illuzzi JL. Effect of 2 stitches vs 1 stitch on the prevention of preterm birth in women with singleton pregnancies who undergo cervical cerclage. Am J Obstet Gynecol. 2008 Apr;198(4):396.e1-7. doi: 10.1016/j.ajog.2007.10.782. Epub 2008 Feb 21.
• Kosinska Kaczynska K, Rebizant B, Bednarek K, Dabrowski FA, Kajdy A, Muzyka-Placzynska K, Filipecka-Tyczka D, Uzar P, Kwiatkowski S, Torbe A, Grzesiak M, Kaczmarek P, Zyla M, Brawura-Biskupski-Samaha R. Emergency cerclage using double-level versus single-level suture in the management of cervical insufficiency (Cervical Occlusion double-level Stitch Application, COSA): study protocol for a multicentre, non-blinded, randomised controlled trial. BMJ Open. 2023 Jun 7;13(6):e071564. doi: 10.1136/bmjopen-2023-071564.

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2022
• Primary Completion (Actual): March 10, 2025
• Study Completion (Actual): March 10, 2025

Study Registration Dates

• First Submitted: January 19, 2022
• First Submitted That Met QC Criteria: February 24, 2022
• First Posted (Actual): March 7, 2022

Study Record Updates

• Last Update Posted (Estimated): September 30, 2025
• Last Update Submitted That Met QC Criteria: September 29, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: pregnancy; premature birth; cervix; pregnancy complication
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Obstetric Labor, Premature; Obstetric Labor Complications; Uterine Diseases; Genital Diseases, Female; Uterine Cervical Diseases; Abortion, Habitual; Abortion, Spontaneous; Premature Birth; Pregnancy Complications; Uterine Cervical Incompetence
• Other Study ID Numbers: nr 1/2022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD share with other researchers will include all IPD that underlie results in a publication
• IPD Sharing Time Frame: Data will become available after completing of recruitment and will be available for 12 months
• IPD Sharing Access Criteria: Data will be available od request sent to the principal researchers. All requests for information will be reviewed by the Study Officials.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No