Cervical Occlusion Double-level Stitch Application

Cervical Incompetence Clinical Trial

— COSA  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05268640
• Other study ID #: nr 1/2022
• Status: Recruiting
• Phase: N/A
• Start date: March 11, 2022
• Est. completion date: February 28, 2025

Study information

• Verified date: May 2023
• Source: Centre of Postgraduate Medical Education
• Contact: Katarzyna Kosinska-Kaczynska, Prof.
• Phone: 22 5690274
• Email: katarzyna.kosinska-kaczynska[@]cmkp.edu.pl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 23+6 weeks. They will be randomized to two arms - McDonald's single cervical cerclage or two-level cerclage.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 78
• Est. completion date: February 28, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• singleton pregnancy,

• gestational age 16+0 to 23+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.

Related Conditions & MeSH terms

• Cervical Incompetence
• Uterine Cervical Incompetence

Intervention

Procedure:
• Double-level cervical cerclage
two cervical sutures + regimen of antibiotics + indomethacin + progesterone
• Single-level cervical cerclage
single cervical suture + regimen of antibiotics + indomethacin + progesterone

Locations

Country	Name	City	State
Poland	Department of Obstetrics, Women's Diseases and Oncological Gynecology, Nicolaus Copernicus University	Bydgoszcz	Kujawsko-pomorskie
Poland	Department of Obstetrics and Gynecology, Oncological Gynecology and Gynecological Endocrinology, Medical University of Gdansk	Gdansk	Pomorskie
Poland	Polish Mother's Memorial Hospital - Research Institute	Lódz	Lodzkie
Poland	Pomeranian Medical University Szczecin	Szczecin	Zachodniopomorskie
Poland	1st Department of Obstetrics and Gynecology, Center of Postagraduate Medical Education	Warsaw	Mazowieckie
Poland	1st Department of Obstetrics and Gynecology, Medical University of Warsaw	Warsaw	Mazowieckie
Poland	Department of Obstetrics, Perinatology and Neonatology, Center of Postagraduate Medical Education	Warsaw	Mazowieckie

Sponsors (6)

Lead Sponsor	Collaborator
Centre of Postgraduate Medical Education	Medical University of Gdansk, Medical University of Warsaw, Nicolaus Copernicus University, Polish Mother Memorial Hospital Research Institute, Pomeranian Medical University Szczecin

Country where clinical trial is conducted

Poland, 

References & Publications (9)

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 — View Citation

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. — View Citation

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.2012.1 — View Citation

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. — View Citation

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 Obste — View Citation

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. — View Citation

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: 10.1 — View Citation

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 — View Citation

Wood SL, Owen J. Cerclage: Shirodkar, McDonald, and Modifications. Clin Obstet Gynecol. 2016 Jun;59(2):302-10. doi: 10.1097/GRF.0000000000000190. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Primary	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	gestational age at delivery	duration of pregnancy untill delivery in weeks and days	observation after intervention for 26 weeks of until birth
Secondary	time from cerclage administration to delivery	time from cerclage administration to delivery in days	observation after intervention for 26 weeks of until birth
Secondary	fetal demise	number and rate of pregnancies complicated by fetal demise	observation after intervention for 26 weeks of until birth
Secondary	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
Secondary	birth weight	neonatal weight at delivery in grams	observation after intervention for 26 weeks of until birth
Secondary	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
Secondary	maternal outcomes	maternal mortality, miscarriage, intrauterine infection, prelabour rupture of membranes, o cervical laceration	observation after intervention for 26 weeks of until birth