Cervical Occlusion Double-level Stitch Application

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Cervical Incompetence

Intervention / Treatment
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* Procedure: Double-level cervical cerclage
* Procedure: Single-level cervical cerclage


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Double-level cerclage<br>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<br>* two cervical sutures + regimen of antibiotics + indomethacin + progesterone<br>|
| Active Comparator: Single-level cerclage<br>single-level cervical cerclage of McDonald technique | Procedure: Single-level cervical cerclage<br>* single cervical suture + regimen of antibiotics + indomethacin + progesterone<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pregnancy, premature birth, cervix, pregnancy complication