C-STICH2: Rescue cervical stitching to prevent miscarriage and premature birth

ISRCTN	ISRCTN12981869
DOI	https://doi.org/10.1186/ISRCTN12981869
EudraCT/CTIS number	2012-005627-32

Submission date: 11/06/2018
Registration date: 13/06/2018
Last edited: 31/10/2024

Recruitment status: No longer recruiting
Overall study status: Ongoing
Condition category: Pregnancy and Childbirth

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
A cervical cerclage is the placement of a stitch to keep the neck of the womb (cervix) closed. A stitch can be placed in a planned way because of a perceived risk of premature birth based on a woman’s pregnancy history or because the neck of the womb is shorter than normal on an ultrasound scan but still closed. Sometimes the neck of the womb can start to open early and the bag of water around the baby (amniotic sac) can come through the neck of womb. If this happens between 16 and 28 weeks of pregnancy an emergency rescue stitch can be performed to try and delay delivery. Prolonging the pregnancy so that the baby can be born when they are bigger and stronger may give them a better chance of surviving and suffering from fewer complications of prematurity. Doctors do not know if a rescue cerclage works. There is some evidence it may prolong pregnancy but it is possible that it may also speed up delivery by causing infection or cause damage to the neck of the womb of the mother. It is therefore very important to perform a study to decide if rescue cerclages delay delivery and if it does whether this benefits the baby (and mother). The best way to work out if rescue cerclage works, and is safe, is to ask women to be randomly allocated to the treatment. This is what we need to do to ensure we know what is best for future women and babies to prevent harm. This study will ask women who have an open neck of the womb with the bag of waters around the baby coming through, to have either a rescue stitch or no rescue stitch the treatment arm will be decided by a process that randomly allocate to one group or the other. All women in the study irrespective of the allocated group will be able to have other treatments that may help prolong pregnancy such as antibiotics, progesterone and medicines that stop the womb contracting (although none of these have been proven to delay labour or improve health of babies). The study team will collect what happens to the mum and baby from their medical notes. All babies will also be reviewed at 2 years of age to assess how they are developing by a postal questionnaire completed by the parents.

Who can participate?
Women who have an open neck of the womb with the bag of waters around the baby coming through at 16-27 weeks of pregnancy..

What does the study involve?
Women will be randomly allocated to receive the stitch or not. All women in the study, whether they have the stitch or not, will be able to have other treatments that may help prolong pregnancy such as antibiotics, progesterone and medicines that stop the womb contracting (although none of these have been proven to delay labour or improve health of babies).

What are the possible benefits and risks of participating?
Risks relating the the rescue cervical cerclage will be detailed to you by the doctor looking after you, but include infection, bleeding, failure to perform the procedure, and rupture of the membranes around your baby leading to delivery of the baby. The potential benefit of rescue cervical cerclage in terms of prolonging pregnancy is not known.

Where is the study run from?
Birmingham Women's Hospital

When is the study starting and how long is it expected to run for?
July 2018 to February 2027

Who is funding the study?
National Institute for Health Research (UK)

Who is the main contact?
Kiran Sunner, K.K.Sunner@bham.ac.uk
(updated 12/04/2021, previously: Dr Katie Morris, r.k.morris@bham.ac.uk)

Study website

Contact information

Mr Kirandeep Sunner
Scientific

Birmingham Clinical Trials Unit
Institute of Applied Health Research
Public Health Building
College of Medical and Dental Sciences
University of Birmingham
Birmingham
B15 2TT
United Kingdom

Phone	+44 (0)121 4159100
Email	K.K.Sunner@bham.ac.uk

Study information

Study design	Randomised controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available at time of registration
Scientific title	C-STICH2: Rescue cervical cerclage to prevent miscarriage and preterm birth: A randomised controlled, multicentre trial (RCT) with internal pilot, a nested qualitative study and cost-effectiveness analysis.
Study acronym	C-STICH2
Study objectives	Does a rescue cervical cerclage prolong pregnancy when performed at 16-28 weeks at amniotic sac prolapse?
Ethics approval(s)	We anticipate submitting for ethics approval on 01/08/2018.
Health condition(s) or problem(s) studied	Obstetrics: Mid Trimester Miscarriage and Preterm Birth
Intervention	Women will be randomised via a web based application provided by the Birmingham Clinical Trials Unit. Women will be randomised to rescue cerclage, an emergency cervical cerclage performed as quickly as feasible, or expectant management which will be pragmatic and involve other treatment at the discretion on the clinician caring for the women.
Intervention type	Procedure/Surgery
Primary outcome measure	Pregnancy loss rate (miscarriage and perinatal mortality, including any stillbirth or neonatal death in the first week of life )
Secondary outcome measures	Maternal (from medical records): 1. Time from conception to pregnancy end (any reason) 2. Miscarriage and pre-viable neonatal death (defined as delivery <24 weeks) 3. Stillbirth (defined as interuterine death >=24 weeks) 4. Gestation at delivery (in live births >= 24 weeks ) 5. Gestational age <28/<32/<37 weeks at delivery (in live births >= 24 weeks) 6. Time from conception to onset of spontaneous vaginal delivery (in live births >= 24 weeks) 7. Sepsis (at any time in pregnancy and until 7 days postnatal) 8. Preterm pre-labour rupture of membranes (PPROM) 9. Gestational age at PPROM 10. Mode of initiation of labour (spontaneous or induced) 11. Mode of delivery (vaginal or operative vaginal or caesarean) 12. Cerclage placement complications (cervical laceration/bleeding from cervix/ruptured membranes/bladder injury) 13. Cerclage removal complications (cervical tears/need for anaesthetic/difficult to remove) 14. Other maternal complications: vaginal bleeding/steroid use/chorioamnionitis/maternal pyrexia of 38°C (intrapartum/postnatal)/systemic infection requiring antibiotics (intrapartum/postnatal)/admission to HDU or ITU (pre/post-delivery) 15. Serious adverse events Neonatal (from medical records): 16. Early neonatal death (defined as a death within 7 days after delivery ) 17. Late neonatal death (defined as a death beyond 7 days and before 28 days after delivery) 18. Birth weight adjusted for gestational age and sex (in live births >= 24 weeks) 19. Small for gestational age and sex (<10th centile; in live births >= 24 weeks) 20. Resuscitation at birth/additional care required (SCBU/NICU/HDU/transitional)/length of stay in additional care 21. Antibiotics within 72 hours/sepsis (clinically diagnosed/proven) 22. Early neurodevelopmental morbidity (severe abnormality on cranial ultrasound scan) 23. Respiratory support (ventilation/CPAP)/days on respiratory support/supplementary oxygen requirements at 36 weeks post-menstrual age 24. Necrotising enterocolitis (Bell’s stage 2 or 3) 25. Retinopathy of prematurity requiring laser treatment/disabilities/congenital abnormalities 26. Serious adverse events Infant (from medical records): 27. Infant death after 28 days until 21 years Child (2-year outcomes collected through a general health questionnaire and PARCA-R): 28. Non-verbal cognition 29. Linguistic skills (from vocabulary and sentence complexity sub-scales) 30. Parent report composite score (from 1 and 2)
Overall study start date	01/07/2018
Completion date	28/02/2027

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	16 Years
Sex	Female
Target number of participants	260
Key inclusion criteria	1. Aged 16 years or older 2. Cervical dilatation with exposed, unruptured foetal membranes 3. Singleton pregnancy 4. Gestational age 16+0 to 27+6 weeks 5. Able to give informed written consent
Key exclusion criteria	1. Contraindication to rescue cerclage as judged by the clinician 2. Cervical cerclage (vaginal or abdominal) inserted earlier in this pregnancy
Date of first enrolment	01/01/2019
Date of final enrolment	31/10/2024

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Katie Morris

Birmingham Women's Hospital
Birmingham
B15 2TT
United Kingdom

Sponsor information

Birmingham Women's and Children's NHS foundation trust.
Hospital/treatment centre

Mindelsohn Way, Birmingham B15 2TG
birmingham
b152TG
England
United Kingdom

Website	https://bwc.nhs.uk/birmingham-womens-hospital
"ROR"	https://ror.org/056ajev02

Funders

Funder type

Government

National Institute for Health Research
Government organisation / National government

Alternative name(s): National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
Location: United Kingdom

Results and Publications

Intention to publish date	01/06/2027
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
Publication and dissemination plan	Planned publication in a high-impact peer-reviewed journal
IPD sharing plan	The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. K.K.Sunner@bham.ac.uk

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Protocol article		11/08/2021	26/09/2023	Yes	No

Editorial Notes

31/10/2024: The following changes were made to the trial record:
1. The overall end date was changed from 31/10/2024 to 28/02/2027.
2. The intention to publish date was changed from 01/06/2025 to 01/06/2027.
3. The plain English summary was updated to reflect these changes.
26/09/2023: The following changes were made to the trial record:
1. The recruitment end date was changed from 01/06/2024 to 31/10/2024.
2. The overall end date was changed from 31/08/2024 to 31/10/2024.
3. The plain English summary was updated to reflect these changes.
4. The participant level data sharing statement was added.
5. The plain English summary was updated to reflect these changes.
12/04/2021: The following changes were made to the trial record:
1. The study contact was updated.
2. The plain English summary was updated to reflect these changes.
12/05/2020: The recruitment to this study is no longer paused.
20/04/2020: Due to current public health guidance, recruitment for this study has been paused.
12/12/2019: The EudraCT number was added.