NicheNCT05312775
Niche In CEsarean Scar Trial (NICEST)
A study testing Double-layer uterine closure and Single-layer uterine closure in people with Niche, run by Nguyen Thi Thu Ha at 1 site in Vietnam.
Trial summary
Rationale: Cesarean delivery (CD) rates are increasing rapidly worldwide. The consequences of cesarean section not only affect the next pregnancies such as uterine rupture or malplacentation but also cause many gynecological complications or infertility due to the formation of cesarean scar defect (CSD) or Niche. Read more about this study
- Who is it for?
- Ages 18 to 60 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Niche
- What is being tested?
- Double-layer uterine closure and Single-layer uterine closure
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 938 participants
- Where
- 1 siteVietnam
- Study dates
- 1 May 2022to Oct 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Pregnant women who undergo a primary CD (planned or unplanned)
- Age ≥ 18 years.
- Gestational age ≥ 37 0/7 weeks
Who cannot join
- Previous major uterine surgery (e.g. laparoscopic or laparotomic fibroid resection, septum resection).
- Women with abnormal menstrual bleeding (e.g. cervical dysplasia, communicating hydrosalpinx, uterine anomaly or endocrine disorders disturbing ovulation, drugs, polyps, fibroids, etc.).
- Women with dysmenorrhea, dyspareunia, suprapubic pain.
- Abnormal placenta: Placenta privia, Placenta percreta… in the current pregnancy.
Trial locations and contacts
1 site in 1 country.
Vietnam1 site, 1 recruiting
- Recruiting
Hanoi Obstetrics and Gynecology Hospital
Hanoi, Hanoi, 100000
Ha TT Nguyen Thi Thu, MD.PhD, 0084989661093, thuha.ivf@gmail.com
Giang TT Duong, MD, 0084972186390, dttgnts41@gmail.com
About this study
Official title: Single Versus Double-layer Closure of The Cesarean Scar In Niche Development: A Randomized Clinical Trial
Rationale: Cesarean delivery (CD) rates are increasing rapidly worldwide. The consequences of cesarean section not only affect the next pregnancies such as uterine rupture or malplacentation but also cause many gynecological complications or infertility due to the formation of cesarean scar defect (CSD) or Niche. One of the major factors for Niche formation is the techniques of hysterotomy closure at the time of cesarean delivery. Most common hysterotomy closures include single and double layers closure. However, there is limited literature to prove which technique decreases niche creation and associated gynecological complications.
Objective: To compare the effect of uterine closure techniques during CD on the formation of Niche evaluated on transvaginal ultrasound and gynecological complications.
Read more
Study design: a double-blinded, single-center, randomized clinical trial. Setting: Hanoi Obstetrics \& Gynecology Hospital (HOGH), Viet Nam. Study population: All women at gestational age ≥ 37 0/7 weeks who undergo a primary CD (planned or unplanned).
Intervention: After informed consent, women will be randomized to either unlocked single layer closure or unlocked double-layer closures of cesarean uterine scar in a 1:1 ratio Primary outcome: The proportion of Niche over time (at 6, 12, 18, 24 months after CD) in the two groups.
Power calculation: A sample size of 389 women is needed for each group. Nature and extent of the burden and risks associated with participation, benefit, and group relatedness: Both uterine closure methods followed by the Vietnam Ministry of Health (VN-MOH), transvaginal ultrasound is also not harmful. It is believed that there are no potential increased risks to patients taking part in this trial because of the standard care and management they receive.
Read the detailed description
Pregnancies at term, indicated for cesarean delivery for the first time, will be fully consulted information related to this study before surgery. Written consent will be obtained from each eligible pregnant woman before randomization into the study.
After signing the informed consent form, eligible women will be randomly assigned in a 1:1 ratio to receive either single-layer closure or double-layer closure, using block randomization with a variable block size of 4, 6. The computer-generated random list will be prepared by an independent statistician who has no other involvement in the study. To ensure allocation concealment, opaque and sealed envelopes will be prepared and controlled by two administrative staff in the Clinical Trial Unit who have no involvement in clinical work. Whenever there is an eligible participant, these two staff will hand over the envelope in sequence to the clinician. As the result, surgeons will not be blinded, but participants and sonographers will be unaware of closure techniques. Apart from randomization, patients will be followed up and treated according to local protocol.
The cesarean section with two uterine scar closure techniques will be performed by well-trained obstetricians. Participants and sonographers will be blinded for the closure technique.
Intervention (double-layer closure) In both study groups, women will undergo a CD following a standard way with respect to the mode of hysterotomy, non-closure of the peritoneum. In the intervention group, double-layer closure of the uterus will be performed using unlocked multifilament continuous running sutures for both layers and the endometrial layer will be included in the first layer. The second layer is a continuous running suture that imbricates the first layer.
Control group (single-layer closure) The control group will receive a single-layer closure using unlocked continuous running multifilament sutures and the endometrial layer will be included.
Complication during surgery
The cases that have complications during surgery will be excluded from the study. Complications encompass:
- Maternal mortality
- Maternal admitted ICU
- Hysterectomy
- Damage to internal organs (bowel, bladder or ureters).
- Complications during postoperative period requiring further surgery. Follow-up Participants will be contacted via telephone to notify about follow-up visits within 10 days of the first day of every menstrual cycle at 6 months, 12 months, 18 months, 24 months (give or take 2 weeks).
Every regular follow-up visit, the participants will be examined and transvaginal ultrasound followed by saline infusion sonohysterography to evaluate Niche. The ultrasound evaluation is standardized as proposed by the latest standard of ISUOG(2019).
Reproductive outcomes at two years follow-up: Percentage of women that conceived at any time during the follow-up duration, time of conception, and results of said pregnancies (ongoing pregnancy, terminated pregnancy due to medical/ social indication).
Niche evaluation Every regular follow-up visit, the participants will be examined and transvaginal ultrasound followed by sonohysterography to evaluate Niche. The Niche evaluation is standardized as proposed by the latest standard of ISUOG(2019).
- Conditions
- Niche
- Being tested
- Double-layer uterine closure, Single-layer uterine closure
- Keywords
- single-layer uterine closure, double-layer uterine closure, niche
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Double-layer uterine closureProcedure or surgery
In the intervention group, double-layer closure of the uterus will be performed using unlocked multifilament continuous running sutures for both layers and the endometrial layer will be included in the first layer. The second layer is a continuous running suture that imbricates the first layer
Single-layer uterine closureProcedure or surgery
The control group will receive a single-layer closure using unlocked continuous running multifilament sutures and the endometrial layer will be included
| Study group | Role | What they receive |
|---|---|---|
| Single-layer uterine closure | Active comparator | Women will undergo a CD following a standard way with respect to the mode of hysterotomy, non-closure of the peritoneum. The control group will receive a single-layer closure using unlocked continuous running multifilament sutures and the endometrial layer will be included Receives: Procedure: Single-layer uterine closure |
| Double-layer uterine closure | Active comparator | Women will undergo a CD following a standard way with respect to the mode of hysterotomy, non-closure of the peritoneum. In the intervention group, double-layer closure of the uterus will be performed using unlocked multifilament continuous running sutures for both layers and the endometrial layer will be included in the first layer. The second layer is a continuous running suture that imbricates the first layer Receives: Procedure: Double-layer uterine closure |
What is being measured
The primary outcome is the main question the study is designed to answer.
The proportion of Niche at 6 months after cesarean delivery of Single-layer uterine closure group
The proportion of Niche at 6 months after cesarean delivery of Single-layer uterine closure group.
Measured: from delivery to 6 months from delivery
The proportion of Niche at 12 months after cesarean delivery of Single-layer uterine closure group
The proportion of Niche at 12 months after cesarean delivery of Single-layer uterine closure group.
Measured: from delivery to 12 months from delivery
The proportion of Niche at 18 months after cesarean delivery of Single-layer uterine closure group
The proportion of Niche at 18 months after cesarean delivery of Single-layer uterine closure group.
Measured: from delivery to 18 months from delivery
The proportion of Niche at 24 months after cesarean delivery of Single-layer uterine closure group
The proportion of Niche at 24 months after cesarean delivery of Single-layer uterine closure group.
Measured: from delivery to 24 months from delivery
The proportion of Niche at 6 months after cesarean delivery of Double-layer uterine closure group
The proportion of Niche at 6 months after cesarean delivery of Double-layer uterine closure group.
Measured: from delivery to 6 months from delivery)
The proportion of Niche at 12 months after cesarean delivery of Double-layer uterine closure group
The proportion of Niche at 12 months after cesarean delivery of Double-layer uterine closure group.
Measured: from delivery to 12 months from delivery
The proportion of Niche at 18 months after cesarean delivery of Double-layer uterine closure group
The proportion of Niche at 18 months after cesarean delivery of Double-layer uterine closure group.
Measured: from delivery to 18 months from delivery
The proportion of Niche at 24 months after cesarean delivery of Double-layer uterine closure group
The proportion of Niche at 24 months after cesarean delivery of Double-layer uterine closure group.
Measured: from delivery to 24 months from delivery
Secondary outcomes (21)
Number of participants with post-partum hemorrhage.
Defined as blood loss more than 1000ml with 24 hours after cesarean delivery
Measured: Within 24 hours from delivery
Number of participants having uterine atony
Defined as use of two or more uterotonics other oxytocin; other surgical interventions such as compression by hand and/or sutures, uterine arteries ligation, embolization, hypogastric arteries ligation, or balloon tamponade
Measured: During operation
Number of participants with maternal infection
Maternal infection as defined:
- Fever: defined as axillary temperature ≥ 37.5 degrees Celsius.
- Start of intravenous broad-spectrum antibiotics (with evidence of infection confirmed by clinical and subclinical presentation)
- Endometritis, myometritis or urinary tract infection (proven positive vaginal discharge/urine culture)
Measured: from delivery until maternal hospital discharge, assessed up to 28 days after delivery
Number of participants having postmenstrual spotting in women with Niche
Postmenstrual spotting is brownish discharge for more than two days at the end of menstruation with a total duration (menstruation and spotting) of more than seven days, or intermenstrual bleeding that starts after the end of menstruation, assessed at 6 months, 12 months, 18 months and 24 months after delivery.
Measured: from delivery to 6 months, 12 months, 18 months, 24 months after cesarean delivery, up to 24 months from delivery
Duration of postmenstrual spotting in women with Niche
Duration of postmenstrual spotting in women with Niche defined as the average number of days of postmenstrual spotting in 6 months, in which duration of postmenstrual spotting in each month will be counted as follows: days with brownish discharge (more than two days) when the total duration of menstruation and spotting exceeds seven days plus days with intermenstrual bleeding, assessed at 6 months, 12 months, 18 months and 24 months after cesarean delivery.
Measured: from delivery to 6 months, 12 months, 18 months, 24 months after cesarean delivery, up to 24 months from delivery
Number of participants suffering from dysmenorrhea in women with Niche
Number of participants suffering from dysmenorrhea in women with Niche, assessed at 6 months, 12 months, 18 months and 24 months after cesarean delivery
Measured: from delivery to 6 months, 12 months, 18 months, 24 months after cesarean delivery, up to 24 months from delivery
Dysmenorrhea severity in women with Niche
Participants with dysmenorrhea self-assessed pain levels and scored 1 to 10 rely on the Numeric Rating Scale (NRS). The average score in span of 6 months will be calculated and the highest score will be noticed to reveal dysmenorrhea severity at 6 months, 12 months, 18 months, 24 months after cesarean delivery
Measured: from delivery to 6 months, 12 months, 18 months, 24 months after cesarean delivery, up to 24 months from delivery
Number of participants suffering from suprapubic pain in women with Niche
Number of participants suffering from suprapubic pain in women with Niche, assessed at 6 months, 12 months, 18 months and 24 months after cesarean delivery
Measured: from delivery to 6 months, 12 months, 18 months, 24 months after cesarean delivery, up to 24 months from delivery
Suprapubic pain severity in women with Niche
Participants with suprapubic pain self-assessed pain levels and scored 1 to 10 rely on the Numeric Rating Scale (NRS). The average score in span of 6 months will be calculated and the highest score will be noticed to reveal suprapubic pain severity at 6 months, 12 months, 18 months, 24 months after cesarean delivery
Measured: from delivery to 6 months, 12 months, 18 months, 24 months after cesarean delivery, up to 24 months from delivery
Number of participants suffering from dyspareunia in women with Niche
Number of participants suffering from dyspareunia in women with Niche, assessed at 6 months, 12 months, 18 months and 24 months after cesarean delivery
Measured: from delivery to 6 months, 12 months, 18 months, 24 months after cesarean delivery, up to 24 months from delivery
Dyspareunia severity in women with Niche
Participants with dyspareunia self-assessed pain levels and scored 1 to 10 rely on the Numeric Rating Scale (NRS). The average score in span of 6 months will be calculated and the highest score will be noticed to reveal dyspareunia severity at 6 months, 12 months, 18 months, 24 months after delivery
Measured: from delivery to 6 months, 12 months, 18 months, 24 months after cesarean delivery, up to 24 months from delivery
Niche length
The length at Niche base will be measured in the sagittal plane on transvaginal ultrasound, assessed at 6 months, 12 months, 18 months and 24 months after cesarean delivery.
Measured: from delivery to 6 months, 12 months, 18 months, 24 months after cesarean delivery, up to 24 months from delivery
Niche depth
The largest depth of Niche will be measured in the sagittal plane on ultrasound, assessed at 6 months, 12 months, 18 months and 24 months after cesarean delivery.
Measured: : from delivery to 6 months, 12 months, 18 months, 24 months after cesarean delivery, up to 24 months from delivery
Number of branches of Niche
Number of branches of Niche will be measured in the transverse plane on transvaginal ultrasound, assessed at 6 months, 12 months, 18 months and 24 months after cesarean delivery.
Measured: from delivery to 6 months, 12 months, 18 months, 24 months after cesarean delivery, up to 24 months from delivery
Residual myometrial thickness (RMT)
Thinnest point of residual myometrial thickness will be measured in the sagittal plane on transvaginal ultrasound, regardless of direction (measured perpendicular to serosa but not necessarily to uterine cavity), from the main Niche or branch with the thinnest RMT. Fibroid is not included in RMT measurement, assessed at 6 months, 12 months, 18 months and 24 months after cesarean delivery.
Measured: from delivery to 6 months, 12 months, 18 months, 24 months after cesarean delivery, up to 24 months from delivery
Ratio of residual myometrial thickness per adjacent myometrial thickness (RMT/AMT)
Adjacent myometrial thickness will be measured close to Niche in the sagittal plane on transvaginal ultrasound, where myometrium is thickness. Ratio of RMT/AMT will be assessed at 6 months, 12 months, 18 months and 24 months after cesarean delivery.
Measured: from delivery to 6 months, 12 months, 18 months, 24 months after cesarean delivery, up to 24 months from delivery
Niche-vesicovaginal fold distance
Distance between Niche and vesicovaginal fold will be measured in the sagittal plane on transvaginal ultrasound, from level of top main Niche (where residual myometrial thickness is smallest (dotted line)) to vesicovaginal fold, assessed at 6 months, 12 months, 18 months and 24 months after cesarean delivery.
Measured: from delivery to 6 months, 12 months, 18 months, 24 months after cesarean delivery, up to 24 months from delivery
Niche-external os distance
Distance between niche and external os will be measured parallel to cervical canal, from most distal point of niche to external os in the sagittal plane on transvaginal ultrasound, assessed at 6 months, 12 months, 18 months and 24 months after cesarean delivery.
Measured: from delivery to 6 months, 12 months, 18 months, 24 months after cesarean delivery, up to 24 months from delivery
Evaluating the correlation between Niche characteristics and gynecological symptoms
Correlation between characteristics of Niche (include length, depth, branches, RMT, RMT/AMT, Niche-vesicovaginal fold distance and Niche-external os distance) and gynecological symptoms (involve postmenstrual spotting, dysmenorrhea, suprapubic pain and dyspareunia) will be analyzed at 6 months, 12 months, 18 months and 24 months after cesarean delivery
Measured: from delivery to 6 months, 12 months, 18 months, 24 months after cesarean delivery, up to 24 months from delivery
Evaluating factors contributing to Niche development
Correlation between Niche formation and risk factors include labor (cervical dilation, duration of labor), planned or unplanned cesarean section, maternal factors, short-term outcomes such as uterine atony, post-partum hemorrhage, post-partum blood transfusion, maternal infection will be analyzed at 6 months, 12 months, 18 months and 24 months after cesarean delivery
Measured: from delivery to 6 months, 12 months, 18 months, 24 months after cesarean delivery, up to 24 months from delivery
Comparison between the rate of niche detection by regular TVUS and sonohysterography
Comparison between rate of niche detection (percentage) in all follow-up events by regular TVUS and sonohysterography
Measured: from delivery to 6 months, 12 months, 18 months, 24 months after cesarean delivery, up to 24 months from delivery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2022
- Study start1 May 2022
- Primary completionApr 2026 (estimated)
- Study completionOct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for NicheStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 938 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nguyen Thi Thu Ha
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Nguyen Thi Thu Ha, Hanoi Obstetrics and Gynecology Hospital
- Investigators
- Anh D Nguyen, PhD. MD, Study director, Hanoi Obstetric and Gynecology HospitalYves Ville, PhD. MD, Study chair, Hôpital Necker-Enfants MaladesHa TT Nguyen, PhD.MD, Principal investigator, Hanoi Obstetric and Gynecology HospitalGiang TT Duong, MD, Principal investigator, Hanoi Obstetric and Gynecology Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05312775
- Sponsor's protocol ID
- PSHN.0005.2021
- Status last verified
- Feb 2024
- First submitted
- 1 Mar 2022
- Last updated
- 1 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Delport S. Global epidemiology of use of and disparities in caesarean sections. Lancet. 2019 Jul 6;394(10192):23-24. doi: 10.1016/S0140-6736(19)30717-2. Epub 2019 Jul 4. No abstract available.
PubMed 31282354Naji O, Wynants L, Smith A, Abdallah Y, Saso S, Stalder C, Van Huffel S, Ghaem-Maghami S, Van Calster B, Timmerman D, Bourne T. Does the presence of a Caesarean section scar affect implantation site and early pregnancy outcome in women attending an early pregnancy assessment unit? Hum Reprod. 2013 Jun;28(6):1489-96. doi: 10.1093/humrep/det110. Epub 2013 Apr 12.
PubMed 23585560Naji O, Wynants L, Smith A, Abdallah Y, Stalder C, Sayasneh A, McIndoe A, Ghaem-Maghami S, Van Huffel S, Van Calster B, Timmerman D, Bourne T. Predicting successful vaginal birth after Cesarean section using a model based on Cesarean scar features examined by transvaginal sonography. Ultrasound Obstet Gynecol. 2013 Jun;41(6):672-8. doi: 10.1002/uog.12423.
PubMed 23371440Roberge S, Demers S, Berghella V, Chaillet N, Moore L, Bujold E. Impact of single- vs double-layer closure on adverse outcomes and uterine scar defect: a systematic review and metaanalysis. Am J Obstet Gynecol. 2014 Nov;211(5):453-60. doi: 10.1016/j.ajog.2014.06.014. Epub 2014 Jun 6.
PubMed 24912096Hesselman S, Hogberg U, Ekholm-Selling K, Rassjo EB, Jonsson M. The risk of uterine rupture is not increased with single- compared with double-layer closure: a Swedish cohort study. BJOG. 2015 Oct;122(11):1535-41. doi: 10.1111/1471-0528.13015. Epub 2014 Aug 4.
PubMed 25088680Clark EA, Silver RM. Long-term maternal morbidity associated with repeat cesarean delivery. Am J Obstet Gynecol. 2011 Dec;205(6 Suppl):S2-10. doi: 10.1016/j.ajog.2011.09.028. Epub 2011 Oct 6.
PubMed 22114995Jordans IPM, de Leeuw RA, Stegwee SI, Amso NN, Barri-Soldevila PN, van den Bosch T, Bourne T, Brolmann HAM, Donnez O, Dueholm M, Hehenkamp WJK, Jastrow N, Jurkovic D, Mashiach R, Naji O, Streuli I, Timmerman D, van der Voet LF, Huirne JAF. Sonographic examination of uterine niche in non-pregnant women: a modified Delphi procedure. Ultrasound Obstet Gynecol. 2019 Jan;53(1):107-115. doi: 10.1002/uog.19049.
PubMed 29536581Bij de Vaate AJ, van der Voet LF, Naji O, Witmer M, Veersema S, Brolmann HA, Bourne T, Huirne JA. Prevalence, potential risk factors for development and symptoms related to the presence of uterine niches following Cesarean section: systematic review. Ultrasound Obstet Gynecol. 2014 Apr;43(4):372-82. doi: 10.1002/uog.13199.
PubMed 23996650Dodd JM, Anderson ER, Gates S, Grivell RM. Surgical techniques for uterine incision and uterine closure at the time of caesarean section. Cochrane Database Syst Rev. 2014 Jul 22;2014(7):CD004732. doi: 10.1002/14651858.CD004732.pub3.
PubMed 25048608Di 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.
PubMed 28070914Hanacek J, Vojtech J, Urbankova I, Krcmar M, Krepelka P, Feyereisl J, Krofta L. Ultrasound cesarean scar assessment one year postpartum in relation to one- or two-layer uterine suture closure. Acta Obstet Gynecol Scand. 2020 Jan;99(1):69-78. doi: 10.1111/aogs.13714. Epub 2019 Sep 26.
PubMed 31441500Stegwee SI, Jordans IPM, van der Voet LF, Bongers MY, de Groot CJM, Lambalk CB, de Leeuw RA, Hehenkamp WJK, van de Ven PM, Bosmans JE, Pajkrt E, Bakkum EA, Radder CM, Hemelaar M, van Baal WM, Visser H, van Laar JOEH, van Vliet HAAM, Rijnders RJP, Sueters M, Janssen CAH, Hermes W, Feitsma AH, Kapiteijn K, Scheepers HCJ, Langenveld J, de Boer K, Coppus SFPJ, Schippers DH, Oei ALM, Kaplan M, Papatsonis DNM, de Vleeschouwer LHM, van Beek E, Bekker MN, Huisjes AJM, Meijer WJ, Deurloo KL, Boormans EMA, van Eijndhoven HWF, Huirne JAF. Single- versus double-layer closure of the caesarean (uterine) scar in the prevention of gynaecological symptoms in relation to niche development - the 2Close study: a multicentre randomised controlled trial. BMC Pregnancy Childbirth. 2019 Mar 4;19(1):85. doi: 10.1186/s12884-019-2221-y.
PubMed 30832681Dahlke JD, Mendez-Figueroa H, Maggio L, Sperling JD, Chauhan SP, Rouse DJ. The Case for Standardizing Cesarean Delivery Technique: Seeing the Forest for the Trees. Obstet Gynecol. 2020 Nov;136(5):972-980. doi: 10.1097/AOG.0000000000004120.
PubMed 33030865
Study at a glance
From the registry record, last updated by the sponsor on 1 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single Versus Double-layer Closure of The Cesarean Scar In Niche Development: A Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT05312775
- Acronym / sponsor ID
- PSHN.0005.2021
- Conditions
- Niche
- Keywords
- single-layer uterine closure, double-layer uterine closure, niche
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 938 participants (estimated)
- Lead sponsor
- Nguyen Thi Thu HaUniversity, hospital or other
- Study start
- 1 May 2022 (actual)
- Primary completion
- Apr 2026 (estimated)
- Study completion
- Oct 2026 (estimated)
- First posted
- 6 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Rationale: Cesarean delivery (CD) rates are increasing rapidly worldwide. The consequences of cesarean section not only affect the next pregnancies such as uterine rupture or malplacentation but also cause many gynecological complications or infertility due to the formation of cesarean scar defect (CSD) or Niche. One of the major factors for Niche formation is the techniques of hysterotomy closure at the time of cesarean delivery. Most common hysterotomy closures include single and double layers closure. However, there is limited literature to prove which technique decreases niche creation and associated gynecological complications.
Objective: To compare the effect of uterine closure techniques during CD on the formation of Niche evaluated on transvaginal ultrasound and gynecological complications.
Study design: a double-blinded, single-center, randomized clinical trial. Setting: Hanoi Obstetrics \& Gynecology Hospital (HOGH), Viet Nam. Study population: All women at gestational age ≥ 37 0/7 weeks who undergo a primary CD (planned or unplanned).
Intervention: After informed consent, women will be randomized to either unlocked single layer closure or unlocked double-layer closures of cesarean uterine scar in a 1:1 ratio Primary outcome: The proportion of Niche over time (at 6, 12, 18, 24 months after CD) in the two groups.
Power calculation: A sample size of 389 women is needed for each group. Nature and extent of the burden and risks associated with participation, benefit, and group relatedness: Both uterine closure methods followed by the Vietnam Ministry of Health (VN-MOH), transvaginal ultrasound is also not harmful. It is believed that there are no potential increased risks to patients taking part in this trial because of the standard care and management they receive.
Detailed description
Pregnancies at term, indicated for cesarean delivery for the first time, will be fully consulted information related to this study before surgery. Written consent will be obtained from each eligible pregnant woman before randomization into the study.
After signing the informed consent form, eligible women will be randomly assigned in a 1:1 ratio to receive either single-layer closure or double-layer closure, using block randomization with a variable block size of 4, 6. The computer-generated random list will be prepared by an independent statistician who has no other involvement in the study. To ensure allocation concealment, opaque and sealed envelopes will be prepared and controlled by two administrative staff in the Clinical Trial Unit who have no involvement in clinical work. Whenever there is an eligible participant, these two staff will hand over the envelope in sequence to the clinician. As the result, surgeons will not be blinded, but participants and sonographers will be unaware of closure techniques. Apart from randomization, patients will be followed up and treated according to local protocol.
The cesarean section with two uterine scar closure techniques will be performed by well-trained obstetricians. Participants and sonographers will be blinded for the closure technique.
Intervention (double-layer closure) In both study groups, women will undergo a CD following a standard way with respect to the mode of hysterotomy, non-closure of the peritoneum. In the intervention group, double-layer closure of the uterus will be performed using unlocked multifilament continuous running sutures for both layers and the endometrial layer will be included in the first layer. The second layer is a continuous running suture that imbricates the first layer.
Control group (single-layer closure) The control group will receive a single-layer closure using unlocked continuous running multifilament sutures and the endometrial layer will be included.
Complication during surgery
The cases that have complications during surgery will be excluded from the study. Complications encompass:
- Maternal mortality
- Maternal admitted ICU
- Hysterectomy
- Damage to internal organs (bowel, bladder or ureters).
- Complications during postoperative period requiring further surgery. Follow-up Participants will be contacted via telephone to notify about follow-up visits within 10 days of the first day of every menstrual cycle at 6 months, 12 months, 18 months, 24 months (give or take 2 weeks).
Every regular follow-up visit, the participants will be examined and transvaginal ultrasound followed by saline infusion sonohysterography to evaluate Niche. The ultrasound evaluation is standardized as proposed by the latest standard of ISUOG(2019).
Reproductive outcomes at two years follow-up: Percentage of women that conceived at any time during the follow-up duration, time of conception, and results of said pregnancies (ongoing pregnancy, terminated pregnancy due to medical/ social indication).
Niche evaluation Every regular follow-up visit, the participants will be examined and transvaginal ultrasound followed by sonohysterography to evaluate Niche. The Niche evaluation is standardized as proposed by the latest standard of ISUOG(2019).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Single-layer uterine closure | Active comparator | Procedure: Single-layer uterine closureWomen will undergo a CD following a standard way with respect to the mode of hysterotomy, non-closure of the peritoneum. The control group will receive a single-layer closure using unlocked continuous running multifilament sutures and the endometrial layer will be included |
| Double-layer uterine closure | Active comparator | Procedure: Double-layer uterine closureWomen will undergo a CD following a standard way with respect to the mode of hysterotomy, non-closure of the peritoneum. In the intervention group, double-layer closure of the uterus will be performed using unlocked multifilament continuous running sutures for both layers and the endometrial layer will be included in the first layer. The second layer is a continuous running suture that imbricates the first layer |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Pregnant women who undergo a primary CD (planned or unplanned)
- Age ≥ 18 years.
- Gestational age ≥ 37 0/7 weeks
Key exclusion criteria (4 listed)
- Previous major uterine surgery (e.g. laparoscopic or laparotomic fibroid resection, septum resection).
- Women with abnormal menstrual bleeding (e.g. cervical dysplasia, communicating hydrosalpinx, uterine anomaly or endocrine disorders disturbing ovulation, drugs, polyps, fibroids, etc.).
- Women with dysmenorrhea, dyspareunia, suprapubic pain.
- Abnormal placenta: Placenta privia, Placenta percreta… in the current pregnancy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Double-layer uterine closureIn the intervention group, double-layer closure of the uterus will be performed using unlocked multifilament continuous running sutures for both layers and the endometrial layer will be included in the first layer. The second layer is a continuous running suture that imbricates the first layer | Procedure or surgery | Double-layer uterine closure |
| Single-layer uterine closureThe control group will receive a single-layer closure using unlocked continuous running multifilament sutures and the endometrial layer will be included | Procedure or surgery | Single-layer uterine closure |
Primary outcome
The proportion of Niche at 6 months after cesarean delivery of Single-layer uterine closure group
Time frame: from delivery to 6 months from delivery
The proportion of Niche at 6 months after cesarean delivery of Single-layer uterine closure group.
The proportion of Niche at 12 months after cesarean delivery of Single-layer uterine closure group
Time frame: from delivery to 12 months from delivery
The proportion of Niche at 12 months after cesarean delivery of Single-layer uterine closure group.
The proportion of Niche at 18 months after cesarean delivery of Single-layer uterine closure group
Time frame: from delivery to 18 months from delivery
The proportion of Niche at 18 months after cesarean delivery of Single-layer uterine closure group.
The proportion of Niche at 24 months after cesarean delivery of Single-layer uterine closure group
Time frame: from delivery to 24 months from delivery
The proportion of Niche at 24 months after cesarean delivery of Single-layer uterine closure group.
The proportion of Niche at 6 months after cesarean delivery of Double-layer uterine closure group
Time frame: from delivery to 6 months from delivery)
The proportion of Niche at 6 months after cesarean delivery of Double-layer uterine closure group.
The proportion of Niche at 12 months after cesarean delivery of Double-layer uterine closure group
Time frame: from delivery to 12 months from delivery
The proportion of Niche at 12 months after cesarean delivery of Double-layer uterine closure group.
The proportion of Niche at 18 months after cesarean delivery of Double-layer uterine closure group
Time frame: from delivery to 18 months from delivery
The proportion of Niche at 18 months after cesarean delivery of Double-layer uterine closure group.
The proportion of Niche at 24 months after cesarean delivery of Double-layer uterine closure group
Time frame: from delivery to 24 months from delivery
The proportion of Niche at 24 months after cesarean delivery of Double-layer uterine closure group.
21 secondary outcomes
Number of participants with post-partum hemorrhage.
Time frame: Within 24 hours from delivery
Number of participants having uterine atony
Time frame: During operation
Number of participants with maternal infection
Time frame: from delivery until maternal hospital discharge, assessed up to 28 days after delivery
Number of participants having postmenstrual spotting in women with Niche
Time frame: from delivery to 6 months, 12 months, 18 months, 24 months after cesarean delivery, up to 24 months from delivery
Duration of postmenstrual spotting in women with Niche
Time frame: from delivery to 6 months, 12 months, 18 months, 24 months after cesarean delivery, up to 24 months from delivery
Number of participants suffering from dysmenorrhea in women with Niche
Time frame: from delivery to 6 months, 12 months, 18 months, 24 months after cesarean delivery, up to 24 months from delivery
Dysmenorrhea severity in women with Niche
Time frame: from delivery to 6 months, 12 months, 18 months, 24 months after cesarean delivery, up to 24 months from delivery
Number of participants suffering from suprapubic pain in women with Niche
Time frame: from delivery to 6 months, 12 months, 18 months, 24 months after cesarean delivery, up to 24 months from delivery
Suprapubic pain severity in women with Niche
Time frame: from delivery to 6 months, 12 months, 18 months, 24 months after cesarean delivery, up to 24 months from delivery
Number of participants suffering from dyspareunia in women with Niche
Time frame: from delivery to 6 months, 12 months, 18 months, 24 months after cesarean delivery, up to 24 months from delivery
Dyspareunia severity in women with Niche
Time frame: from delivery to 6 months, 12 months, 18 months, 24 months after cesarean delivery, up to 24 months from delivery
Niche length
Time frame: from delivery to 6 months, 12 months, 18 months, 24 months after cesarean delivery, up to 24 months from delivery
Niche depth
Time frame: : from delivery to 6 months, 12 months, 18 months, 24 months after cesarean delivery, up to 24 months from delivery
Number of branches of Niche
Time frame: from delivery to 6 months, 12 months, 18 months, 24 months after cesarean delivery, up to 24 months from delivery
Residual myometrial thickness (RMT)
Time frame: from delivery to 6 months, 12 months, 18 months, 24 months after cesarean delivery, up to 24 months from delivery
Ratio of residual myometrial thickness per adjacent myometrial thickness (RMT/AMT)
Time frame: from delivery to 6 months, 12 months, 18 months, 24 months after cesarean delivery, up to 24 months from delivery
Niche-vesicovaginal fold distance
Time frame: from delivery to 6 months, 12 months, 18 months, 24 months after cesarean delivery, up to 24 months from delivery
Niche-external os distance
Time frame: from delivery to 6 months, 12 months, 18 months, 24 months after cesarean delivery, up to 24 months from delivery
Evaluating the correlation between Niche characteristics and gynecological symptoms
Time frame: from delivery to 6 months, 12 months, 18 months, 24 months after cesarean delivery, up to 24 months from delivery
Evaluating factors contributing to Niche development
Time frame: from delivery to 6 months, 12 months, 18 months, 24 months after cesarean delivery, up to 24 months from delivery
Comparison between the rate of niche detection by regular TVUS and sonohysterography
Time frame: from delivery to 6 months, 12 months, 18 months, 24 months after cesarean delivery, up to 24 months from delivery
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Mar 2024.
- Background: PubMed 31282354Delport S. Global epidemiology of use of and disparities in caesarean sections. Lancet. 2019 Jul 6;394(10192):23-24. doi: 10.1016/S0140-6736(19)30717-2. Epub 2019 Jul 4. No abstract available.
- Background: PubMed 23585560Naji O, Wynants L, Smith A, Abdallah Y, Saso S, Stalder C, Van Huffel S, Ghaem-Maghami S, Van Calster B, Timmerman D, Bourne T. Does the presence of a Caesarean section scar affect implantation site and early pregnancy outcome in women attending an early pregnancy assessment unit? Hum Reprod. 2013 Jun;28(6):1489-96. doi: 10.1093/humrep/det110. Epub 2013 Apr 12.
- Background: PubMed 23371440Naji O, Wynants L, Smith A, Abdallah Y, Stalder C, Sayasneh A, McIndoe A, Ghaem-Maghami S, Van Huffel S, Van Calster B, Timmerman D, Bourne T. Predicting successful vaginal birth after Cesarean section using a model based on Cesarean scar features examined by transvaginal sonography. Ultrasound Obstet Gynecol. 2013 Jun;41(6):672-8. doi: 10.1002/uog.12423.
- Background: PubMed 24912096Roberge S, Demers S, Berghella V, Chaillet N, Moore L, Bujold E. Impact of single- vs double-layer closure on adverse outcomes and uterine scar defect: a systematic review and metaanalysis. Am J Obstet Gynecol. 2014 Nov;211(5):453-60. doi: 10.1016/j.ajog.2014.06.014. Epub 2014 Jun 6.
- Background: PubMed 25088680Hesselman S, Hogberg U, Ekholm-Selling K, Rassjo EB, Jonsson M. The risk of uterine rupture is not increased with single- compared with double-layer closure: a Swedish cohort study. BJOG. 2015 Oct;122(11):1535-41. doi: 10.1111/1471-0528.13015. Epub 2014 Aug 4.
- Background: PubMed 22114995Clark EA, Silver RM. Long-term maternal morbidity associated with repeat cesarean delivery. Am J Obstet Gynecol. 2011 Dec;205(6 Suppl):S2-10. doi: 10.1016/j.ajog.2011.09.028. Epub 2011 Oct 6.
- Background: PubMed 29536581Jordans IPM, de Leeuw RA, Stegwee SI, Amso NN, Barri-Soldevila PN, van den Bosch T, Bourne T, Brolmann HAM, Donnez O, Dueholm M, Hehenkamp WJK, Jastrow N, Jurkovic D, Mashiach R, Naji O, Streuli I, Timmerman D, van der Voet LF, Huirne JAF. Sonographic examination of uterine niche in non-pregnant women: a modified Delphi procedure. Ultrasound Obstet Gynecol. 2019 Jan;53(1):107-115. doi: 10.1002/uog.19049.
- Background: PubMed 23996650Bij de Vaate AJ, van der Voet LF, Naji O, Witmer M, Veersema S, Brolmann HA, Bourne T, Huirne JA. Prevalence, potential risk factors for development and symptoms related to the presence of uterine niches following Cesarean section: systematic review. Ultrasound Obstet Gynecol. 2014 Apr;43(4):372-82. doi: 10.1002/uog.13199.
- Background: PubMed 25048608Dodd JM, Anderson ER, Gates S, Grivell RM. Surgical techniques for uterine incision and uterine closure at the time of caesarean section. Cochrane Database Syst Rev. 2014 Jul 22;2014(7):CD004732. doi: 10.1002/14651858.CD004732.pub3.
- Background: PubMed 28070914Di 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.
- Background: PubMed 31441500Hanacek J, Vojtech J, Urbankova I, Krcmar M, Krepelka P, Feyereisl J, Krofta L. Ultrasound cesarean scar assessment one year postpartum in relation to one- or two-layer uterine suture closure. Acta Obstet Gynecol Scand. 2020 Jan;99(1):69-78. doi: 10.1111/aogs.13714. Epub 2019 Sep 26.
- Background: PubMed 30832681Stegwee SI, Jordans IPM, van der Voet LF, Bongers MY, de Groot CJM, Lambalk CB, de Leeuw RA, Hehenkamp WJK, van de Ven PM, Bosmans JE, Pajkrt E, Bakkum EA, Radder CM, Hemelaar M, van Baal WM, Visser H, van Laar JOEH, van Vliet HAAM, Rijnders RJP, Sueters M, Janssen CAH, Hermes W, Feitsma AH, Kapiteijn K, Scheepers HCJ, Langenveld J, de Boer K, Coppus SFPJ, Schippers DH, Oei ALM, Kaplan M, Papatsonis DNM, de Vleeschouwer LHM, van Beek E, Bekker MN, Huisjes AJM, Meijer WJ, Deurloo KL, Boormans EMA, van Eijndhoven HWF, Huirne JAF. Single- versus double-layer closure of the caesarean (uterine) scar in the prevention of gynaecological symptoms in relation to niche development - the 2Close study: a multicentre randomised controlled trial. BMC Pregnancy Childbirth. 2019 Mar 4;19(1):85. doi: 10.1186/s12884-019-2221-y.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anh D Nguyen, PhD. MD study director
Hanoi Obstetric and Gynecology Hospital
Yves Ville, PhD. MD study chair
Hôpital Necker-Enfants Malades
Ha TT Nguyen, PhD.MD principal investigator
Hanoi Obstetric and Gynecology Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Double-layer uterine closure and Single-layer uterine closure in people with Niche, run by Nguyen Thi Thu Ha at 1 site in Vietnam.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 1 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Vietnam. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ha TT Nguyen, PhD.MD (0989661093, dr.hanguyen@hogh.vn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The proportion of Niche at 6 months after cesarean delivery of Single-layer uterine closure group (time frame: from delivery to 6 months from delivery). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05312775, which also lists 13 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Mar 2024.