Clinical trial NCT05268640: Cervical Occlusion Double-level Stitch Application
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Cervical Incompetence
Keywords: pregnancy
premature birth
cervix
pregnancy complication
Lead sponsor: Centre of Postgraduate Medical Education
Sponsor class: OTHER
Collaborators: name: Pomeranian Medical University Szczecin
name: Polish Mother Memorial Hospital Research Institute
name: Medical University of Warsaw
name: Medical University of Gdansk
name: Nicolaus Copernicus University
First posted: 2022-03-07
Enrollment: 78
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: deliveries below 34+0 weeks of gestation
timeFrame: observation after intervention for 26 weeks of until birth
Secondary outcomes:
measure: gestational age at delivery
timeFrame: observation after intervention for 26 weeks of until birth
measure: time from cerclage administration to delivery
timeFrame: observation after intervention for 26 weeks of until birth
measure: fetal demise
timeFrame: observation after intervention for 26 weeks of until birth
measure: neonatal outcomes
timeFrame: observation after intervention for 26 weeks of until birth
measure: birth weight
timeFrame: observation after intervention for 26 weeks of until birth
measure: 5th minute Apgar score
timeFrame: observation after intervention for 26 weeks of until birth
measure: maternal outcomes
timeFrame: observation after intervention for 26 weeks of until birth
Other outcomes:
measure: cerclage procedure complications occurring within 48 hours after cerclage placement
timeFrame: observation after intervention for 48 hours
Locations:
city: Bydgoszcz
country: Poland
facility: Department of Obstetrics, Women's Diseases and Oncological Gynecology, Nicolaus Copernicus University
state: Kujawsko-pomorskie
city: Warsaw
country: Poland
facility: 1st Department of Obstetrics and Gynecology, Center of Postagraduate Medical Education
state: Mazowieckie
city: Warsaw
country: Poland
facility: Department of Obstetrics, Perinatology and Neonatology, Center of Postagraduate Medical Education
state: Mazowieckie
city: Warsaw
country: Poland
facility: 1st Department of Obstetrics and Gynecology, Medical University of Warsaw
state: Mazowieckie
city: Gdańsk
country: Poland
facility: Department of Obstetrics and Gynecology, Oncological Gynecology and Gynecological Endocrinology, Medical University of Gdansk
state: Pomorskie
city: Szczecin
country: Poland
facility: Pomeranian Medical University Szczecin
state: Zachodniopomorskie
city: Łódź
country: Poland
facility: Polish Mother's Memorial Hospital - Research Institute
state: Łodzkie
Study officials:
affiliation: Center of Postgraduate Medical Education
name: Katarzyna Kosinska Kaczynska, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Center of Postgraduate Medical Education
name: Anna Kajdy, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Pomeranian Medical University Szczecin
name: Sebastian Kwiatkowski, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Polish Mother's Memorial Hospital - Research Institute
name: Mariusz Grzesiak, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
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.
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: 10.1016/j.ejogrb.2007.11.009. Epub 2008 Feb 20.
citation: 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.
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 Obstet Gynecol. 2019 Aug;221(2):140.e1-140.e18. doi: 10.1016/j.ajog.2019.03.017. Epub 2019 Mar 28.
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.
citation: Wood SL, Owen J. Cerclage: Shirodkar, McDonald, and Modifications. Clin Obstet Gynecol. 2016 Jun;59(2):302-10. doi: 10.1097/GRF.0000000000000190.
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.
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.2012.11.039. Epub 2012 Nov 28.
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/j.ajog.2007.10.782. Epub 2008 Feb 21.