Clinical trial NCT03629028: Single or Double-layer Uterine Closure Techniques
Official title: Single or Double-layer Uterine Closure Techniques Following Cesarean: An Ongoing Debate
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Uterine Scar
Cesarean Section Complications
Cesarean Section; Dehiscence
Keywords: cesarean section, niche, isthmocele, uterine closure
Lead sponsor: Baskent University
Sponsor class: OTHER
First posted: 2018-08-14
Enrollment: 282
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective Randomised Trial
Primary purpose: PREVENTION

Brief summary: There are different surgical techniques of uterine closure during cesarean. A growing data has suggested that the closure technique has an effect on uterine scar healing. Residual myometrium thickness and uterine scar defect (niche) development seems to be related to the single or double layer closure of uterus. In that study, investigators will search for the effect of single or double layer closure of uterus during cesarean on the uterine scar defect.

Detailed description: Study design and participants This study will be assessed cesarean delivery (CD) patients who will admit to the Obstetrics and Gynecology Clinic of the Başkent University Adana Dr. Turgut Noyan Research and Application Center between July 2018 and September 2019. Specifically, participants will be singleton pregnancy patients between 18-45 years of age who will be in gestational weeks 24-41 and had not previously received any uterine operations such as CS or myomectomy. Patients with multiple pregnancies and/or chronic inflammatory diseases such as systemic lupus erythematosus, rheumatoid arthritis, and insulin-dependent diabetes mellitus will be excluded. All patients who meet the inclusion criteria will be randomized into two treatment groups (i.e., single- or double-layer closures).

This study was approved by Başkent University Institutional Review Board and Ethics Committee (Project no= KA18-71, Approval Date= 7/27/2018), and supported by Başkent University Research Fund. Patients who will agree to participate in the study will be informed about the purpose of the study before their operations, and each provided signed written consent.

Participants will be also assessed for maternal age, gravidity, parity, body mass index, smoking status, diabetes mellitus, hypertensive diseases of pregnancy, and medical history. Regardless of whether they had contractions before surgery, this study also will be determined patient CD indications, levels of cervical dilatation, and how CD will be established (i.e., elective or emergent).

Randomization and masking A table of random numbers is used as a simple randomization method for placing participants into the two treatment groups. The Research Randomizer website (https://www.randomizer.org/) was used to create this table. Before the intervention, the next envelope among a previously prepared, sealed, and the number-ordered stack will be opened by a nurse for each procedure.

Surgery technique Six operators will perform CD operations. Access to the abdomen will be achieved via Pfannenstiel incision, while the Kerr incision technique will be applied to the uterus for all patients. Patients in the single-layer group will be received uterus closures with locking, while patients in the double-layer group will be received uterus closures with locking in the first layer, but without locking and using the Lambert style in the second layer. The decidua will be deliberately excluded during all suturations. A synthetic absorbable suture material (Vicryl 1.0, Ethicon, Somerville, NJ, USA) will be used during all uterus closures, with corner stitches that will be applied to all patients. Additional suture usages and numbers will be reported only in cases of bleeding. Both uterine closure and whole operation times will be recorded by the respective operating room technicians. Finally, intravenous prophylactic antibiotics (2 g cefazolin sodium) and uterotonic medications (10 IU oxytocin) will be routinely applied during all CD procedures.

Follow-up Postoperative follow-ups will be completed in March 2020. All participants will be called after delivery and will be invited to complete sixth-month evaluations. However, participants who will experience post-CD pregnancies or uterine surgeries will be excluded. All remaining participants will be examined at six to nine months period after CD for niche presence in the scar region, niche measurements, scar shape, distance between niche and the external cervical os and residual myometrium thickness (RMT), and adjacent myometrium thicknesses (AMT). The distance between the niche and external os should be measured parallel to the top of the main niche, from the most distal niche point to external os. These examinations will be conducted by two experienced sonographers who will be blinded to clinical information regarding the closure technique. Procedures will be specifically completed using a 4-10 MHz transducer (E8C-RS micro convex endocavity probe, Voluson S6, GE, Milwaukee, US), ultrasonography, and through the saline infusion sonohysterography (SIS) method. The cervix will be first cleaned with povidone iodine while the patient will be on the gynecological examination table prior to ultrasonography. The SIS process then will be progressed toward the inside of the endometrial cavity by passing from the cervical os with an intrauterine insemination cannula (intrauterine insemination catheter, Wallace Artificial Insemination Catheter, Smiths Medical International Ltd., Ashford, Kent, UK). A sterile saline solution will be applied to sufficiently distend the cavity, while ultrasonography will be conducted via transvaginal probe. At this time, the presence of a hypoechogenic area with a depth of 2mm or deeper in the CD scar region within the endometrial cavity will be accepted as a niche. Niche dimensions will be determined via 3-axis measurements for depth, length, and width. Niche shape, distance to the external cervical os, RMT, and AMT will be evaluated. During these follow-ups, patients will be also asked about their menstruation processes and any experiences of cervical pain, menstruation pain, postmenstrual bleeding (PMB) in the form of spotting, and other abnormal bleeding patterns. Those who will experience bleeding for two days or more in the form of spotting after menstruation will be defined as PMB. Participants who will use intrauterine devices after CD and/or those who could not tolerate speculum application will be examined via transvaginal ultrasonography (TV USG).

Outcomes Primary outcomes will be considered niche presence and measurements, while secondary outcomes will be considered RMT, AMT, healing ratio, postmenstrual spotting, and dysmenorrhea.

Statistical analyses The sample size was calculated based on a study by Di Spiezio Sardo et al. (2017) titled Risk of Cesarean Scar Defect Following Single- vs Double-Layer Uterine Closure: Systematic Review and Meta-Analysis of Randomized Controlled Trials. Their study revealed niche formation rates for single- and double-layer closure types of 25% and 43%, respectively. Based on tools available at the Power and Sample Size website (http://powerandsamplesize.com/Calculators), the needed sample size was calculated at 141 for each treatment group with 90% power and 0.05 alpha error.

All data were statistically analyzed using the IBM SPSS 21.0 software. Categorical measurements will be presented as frequencies and percentages, while continuous measurements will be summarized as means and standard deviations (median and range when needed). Distributions will be checked and the student's t-test was will be used for variables meeting the parametric test assumptions when comparing the continuous measurements based on groups, while the Mann Whitney U test will be used for those that will not meet the parametric test assumptions. Finally, chi-square or Fisher's test statistics will be used to compare categorical variables. Statistical significance is set to 0.05 for all tests.

Eligibility criteria: Inclusion Criteria:

* Primary cesarean, singleton pregnancy,

Exclusion Criteria:

* Multiple pregnancy, History of any uterine surgery, wound healing diseases (insulin dependent diabetes mellitus, rheumatoid arthritis, systemic lupus erythematous, inflammatory bowel disease)

Primary outcomes:
measure: Number of Participants With Niche Visualized by Saline Infusion Sonography
timeFrame: 6 to 9 months
measure: Median Depth of Niche
timeFrame: 6-9 months
measure: Median Length of Niche
timeFrame: 6-9 months
measure: Median Width of Niche in Transverse Plane
timeFrame: 6-9 months
Secondary outcomes:
measure: Residual Myometrium Thickness - 6 to 9 Months
timeFrame: 6 to 9 months
measure: Adjacent Myometrium Thickness
timeFrame: 6 to 9 months
Other outcomes:
Locations:
city: Adana
country: Turkey
facility: Baskent University Adana Seyhan Uygulama Hastanesi
Study officials:
affiliation: Baskent University Department of Obstetrics and Gynecology
name: Şafak YILMAZ BARAN, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Di Spiezio Sardo A, Saccone G, McCurdy R, Bujold E, Bifulco G, Berghella V. Risk of Cesarean scar defect following single- vs double-layer uterine closure: systematic review and meta-analysis of randomized controlled trials. Ultrasound Obstet Gynecol. 2017 Nov;50(5):578-583. doi: 10.1002/uog.17401. Epub 2017 Oct 9.