Condition category
Pregnancy and Childbirth
Date applied
27/11/2014
Date assigned
03/12/2014
Last edited
22/09/2017
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Every year about 3750 women in the UK will have complications where their cervix (the neck of the womb) becomes loose and opens during the early months of pregnancy. This can require a stitch being sewn into the cervix in an attempt to keep it closed. This is often referred to as ‘cervical suture’ or ‘cervical cerclage’. If this procedure is not performed the cervix can open too early and can result in a miscarriage or premature birth. Inserting a stitch into the cervix does not guarantee to keep the cervix closed, but it can sometimes allow the pregnancy to continue for a few more weeks. The stitches used for this procedure are available in different sizes and materials. Some of the stitch threads are made from a single, smooth fibre (e.g. nylon) while others are composed of many fibres which are woven to form a fine braided or net-like structure. A survey of consultants in the UK has shown most use braided threads when they stitch the cervix merely because it is the traditional material used and because it is thought to offer strength and enhanced support to an otherwise loose cervix. However, this survey also revealed that some surgeons thought that bacteria could grow more easily in the spaces of the braided thread than on the surface of the monofilament line. This could increase the risk of infection, which might cause an early labour. It is therefore essential to investigate whether the type of thread used for stitching the cervix increases or decreases the risk of infection. This study will therefore compare outcomes from the use of either smooth or braided stitches during this procedure.

Who can participate?
Eligible pregnant women can opt to be part of the study if they are due a planned stitch in their cervix between 12 and 22 weeks into their pregnancy.

What does the study involve?
The best way to compare the two methods of treatment is to undertake a clinical trial where the nature of the stitch used is decided randomly. Participants will be randomly allocated to receive either a monofilament suture or a braided suture to place a cervical cerclage. Apart from the type of thread used, participants will receive identical medical treatment to those not taking part in the study. Information will be collected concerning the risk of losing a baby during pregnancy or within a week of birth, the number of weeks the pregnancy lasted prior to birth, whether the baby was admitted to a Neonatal Unit, the length of stay in the unit and any sign of vaginal or womb infection.

What are the possible benefits and risks of participating?
As any participant has been advised that they will need a cervical stitch they will not gain any additional benefit by taking part in the study. Similarly, there are no additional risks associated with taking part above those associated with the cerclage itself. Seeing what bacteria grow on the vaginal swab and removed stitch will help doctors decide if the woman taking part in the study needs any antibiotics. By taking part participants will help doctors decide which is best type of thread to offer to women requiring a cervical stitch in the future. The results of this study can potentially save the lives of more than 300 babies a year in the UK alone who would otherwise be at risk of severe prematurity or miscarriage.

Where is the study run from?
Abertawe Bro Morgannwg University Health Board, Aneurin Bevan University Health Board, Barking, Havering and Redbridge University Hospitals NHS Trust, Barts Health NHS Trust, Bedford Hospital NHS Trust, Betsi Cadwaladr University Health Board, Birmingham Women’s and Children’s NHS Foundation Trust, Blackpool Teaching Hospitals NHS Foundation Trust, Bolton NHS Foundation Trust, Central Manchester University Hospitals NHS Trust, Chelsea and Westminster Hospital NHS Foundation Trust, City Hospitals Sunderland NHS Foundation Trust, East Lancashire Hospitals NHS Trust, Epsom and St Helier University Hospitals NHS Trust, Guy's and St Thomas' NHS Foundation Trust, Heart of England NHS Foundation Trust, Imperial College Healthcare NHS Trust, Kettering General Hospital NHS Trust, Kingston Hospital NHS Foundation Trust, Lancashire Teaching Hospitals NHS Foundation Trust, Leeds Teaching Hospitals NHS Trust, Lewisham and Greenwich NHS Trust, Liverpool Women's NHS Foundation Trust, Luton and Dunstable University Hospital NHS Foundation Trust, Mid Essex Hospitals NHS Trust, Milton Keynes University Hospital NHS Foundation Trust, NHS Fife, NHS Grampian, NHS Lothian, Northern Devon Healthcare NHS Trust, Nottingham University Hospitals NHS Foundation Trust, Pennine Acute Hospitals NHS Trust, Portsmouth Hospitals NHS Trust, Princess Alexandra Hospital NHS Trust, Sandwell and West Birmingham Hospitals NHS Trust, The Mid Yorkshire Hospitals NHS Trust, The Newcastle Upon Tyne NHS Foundation Trust, The Royal Wolverhampton NHS Trust, The Shrewsbury and Telford Hospital NHS Trust, Torbay and South Devon NHS Foundation Trust, University College London Hospitals NHS Foundation Trust, University Hospitals Bristol NHS Foundation Trust, University Hospitals Coventry and Warwickshire NHS Trust, University Hospitals of Leicester NHS Trust, Warrington and Halton Hospitals NHS Foundation Trust, Western Sussex Hospitals NHS Trust, Worcestershire Acute Hospitals NHS Trust, York Teaching Hospital NHS Foundation Trust.

When is the study starting and how long is it expected to run for?
March 2015 to October 2018

Who is funding the study?
NIHR Health Technology Assessment Programme - HTA (UK)

Who is the main contact?
1. Ms Joy Rahman (public)
J.K.Rahman@bham.ac.uk
2. Mr Phil Toozs-Hobson (scientific)

Trial website

http://www.birmingham.ac.uk/C-Stich

Contact information

Type

Public

Primary contact

Ms Joy Rahman

ORCID ID

Contact details

Birmingham Clinical Trials Unit
Institute of Applied Health Research
University of Birmingham
Birmingham
B15 2TT
United Kingdom
+44 (0)1214148335
J.K.Rahman@bham.ac.uk

Type

Scientific

Additional contact

Mr Phil Toozs-Hobson

ORCID ID

Contact details

Birmingham Women’s and Children’s Hospital NHS Foundation Trust
Birmingham Women’s Hospital
Mindelsohn Way
Edgbaston
Birmingham
B15 2TG
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

5.0; HTA 13/04/107

Study information

Scientific title

Cerclage Suture Type for an Insufficient Cervix and its effect on Health outcomes (C-STICH)

Acronym

C-STICH

Study hypothesis

Every year approximately 3750 women in the UK will have complications where their cervix (the neck of the womb) becomes loose and opens during the early months of pregnancy. This can require a stitch being sewn into the cervix in an attempt to keep it closed. This is often referred to as ‘cervical suture’ or ‘cervical cerclage’. If this procedure is not performed the cervix can open too early and can result in a miscarriage or premature birth. Inserting a stitch into the cervix does not guarantee to keep the cervix closed, but it can sometimes allow the pregnancy to continue for a few more weeks.

The stitches used for this procedure are available in different sizes and materials. Some of the stitch threads are made from a single, smooth fibre (e.g. nylon) while others are composed of many fibres which are woven to form a fine braided or net-like structure. A survey of consultants in the UK has shown most use braided threads when they stitch the cervix merely because it is the traditional material used and because it is thought to offer strength and enhanced support to an otherwise loose cervix. However, this survey also revealed that some surgeons thought that bacteria could grow more easily in the spaces of the braided thread than on the surface of the monofilament line. This could increase the risk of infection which might cause an early labour. It is therefore essential to investigate whether thread-type used for stitching the cervix increases or decreases risk of infection.

More details can be found at http://www.nets.nihr.ac.uk/projects/hta/1304107
Protocol can be found at http://www.birmingham.ac.uk/Documents/college-mds/trials/bctu/C-stich/CSTICH-protocol-V5.0-23-Mar-2017-clean.pdf

Ethics approval

Cambridgeshire & Hertfordshire (East of England), 04/03/2015, ref: 14/EE/1293

Study design

Multicentre open randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

http://www.birmingham.ac.uk/Documents/college-mds/trials/bctu/C-stich/C-STICH-PIS-V4.0-23-Mar-2017-clean.doc

Condition

Insufficient cervix

Intervention

Participants will be randomly allocated to receive either a monofilament suture or a braided suture to place a cervical cerclage. Apart from the type of thread used, participants will receive identical medical treatment to those not taking part in the study. Information will be collected concerning the risk of losing a baby during pregnancy or within a week of birth, the number of weeks the pregnancy lasted prior to birth, whether the baby was admitted to a Neonatal Unit, the length of stay in the unit and any sign of vaginal or womb infection.

Intervention type

Procedure/Surgery

Phase

Drug names

Primary outcome measure

Pregnancy loss rate (i.e. miscarriage and perinatal mortality, defined as any stillbirth or neonatal death in the first week of life), collected from the medical records at 7 days after delivery

Secondary outcome measures

Current secondary outcome measures as of 22/09/2017:

Maternal outcomes, collected at discharge from hospital or 7 days, whichever is sooner:
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 outcomes, collected from the medical records at 28 days for babies born at term and at the estimated delivery date for babies born preterm:
1. Early neonatal death (defined as a death within 7 days after delivery)
2. Late neonatal death (defined as a death beyond 7 days and before 28 days after delivery)
3. Birth weight adjusted for gestational age and sex (in live births >= 24 weeks)
4. Small for gestational age and sex (<10th centile; in live births >= 24 weeks)
5. Resuscitation at birth/additional care required (SCBU/NICU/HDU/transitional)/length of stay in additional care
6. Antibiotics within 72 hours/sepsis (clinically diagnosed/proven)
7. Early neurodevelopmental morbidity (severe abnormality on cranial ultrasound scan)
8. Respiratory support (ventilation/CPAP)/days on respiratory support/supplementary oxygen requirements at 36 weeks post menstrual age
9. Necrotising enterocolitis (Bell’s stage 2 or 3)
10. Retinopathy of prematurity requiring laser treatment/disabilities/congenital abnormalities
11. Serious adverse events

Microbiological outcomes, measured at cerclage placement and removal:
Full cultures will be undertaken to identify the complete range of potentially pathogenic bacteria isolated from the suture, and high vaginal area. The likely significance of microorganisms isolated from each clinical sample will be assessed in the context of clinical evidence of infection in the mother and her baby.

Previous secondary outcome measures:

Maternal:
1. Gestation at delivery
2. Mode of initiation of labour
3. Mode of delivery
4. Adverse events: suture-related cervical tears, chorioamnionitis, maternal pyrexia of 38C, systemic infection requiring antibiotics (infection parameters based on Centre for Disease Control/National Healthcare Safety Network [CDC/NHSN] guidance)

Neonatal:
1. Late neonatal death, defined as a death beyond 7 days and before 28 days after delivery
2. Length of stay in neonatal unit (including level of care)
3. Severe abnormality on cranial ultrasound scan
4. Oxygen dependency at 36 weeks corrected gestation
5. Necrotising enterocolitis (Bell’s stage 2 or 3)
6. Retinopathy of prematurity requiring laser treatment

Microbiological:
Full cultures will be undertaken to identify the complete range of potentially pathogenic bacteria isolated from the suture and cervix. The likely significance of microorganisms isolated from each clinical sample will be assessed in the context of clinical evidence of infection in the mother and her baby.

Overall trial start date

01/03/2015

Overall trial end date

01/10/2018

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Singleton pregnancy
2. Indication for cervical cerclage (any of the below):
2.1. A history of three or more previous midterm losses or premature births (≤ 28 weeks)
2.2. Insertion of cervical sutures in previous pregnancies
2.3. A history of midtrimester loss or premature birth with a shortened (≤ 25 mm) cervix
2.4. Women whom clinicians deem to be at risk of preterm birth either by history or the results of an ultrasound scan and in whom the placement of a cervical cerclage is considered the most appropriate treatment
3. Aged 18 and over

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

900

Participant exclusion criteria

Current exclusion criteria as of 07/06/2017:
1. Women who have taken part in C-STICH previously
2. Women aged less than 18 years old at the time of presentation
3. Those with a multiple pregnancy
4. Those requiring a rescue cerclage*
5. Women who are unwilling or unable to give informed consent
6. Those in whom a cerclage will be placed by any route other than vaginally (e.g. via an abdominal route)
7. Immediate need for insertion of a suture**
8. Women who have membranes that have ruptured or are surfacing***
* For study purposes, rescue cerclage is defined as: emergency cerclage where stitches are inserted in women who have had their preterm labours (e.g. uterine contractions, progressive cervical dilatation, bulging membranes) sufficiently halted by tocolysis or other means between 15 and 28 weeks.
** Immediate need for insertion of a suture should not be delayed by the trial (thus, if giving information about the trial and waiting for the participant to decide upon whether or not she wants to participate will delay the insertion of an urgently needed suture, then treatment should go ahead and the woman should be excluded from the trial).
***Woman with membranes that are ruptured or bulging through the external OS should have a rescue cerclage and be excluded from trial participation.

Previous exclusion criteria:
1. Women aged less than 16 years old at the time of presentation
2. Those with a multiple pregnancy
3. Those requiring a rescue cerclage
4. Women who are unwilling or unable to give informed consent

Recruitment start date

01/03/2015

Recruitment end date

31/01/2018

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Birmingham Women's Hospital
Birmingham
B15 2TG
United Kingdom

Trial participating centre

Royal Infirmary
Edinburgh
EH16 4SA
United Kingdom

Trial participating centre

Leeds General Infirmary
Leeds
LS1 3EX
United Kingdom

Trial participating centre

Royal Victoria Infirmary
Newcastle upon Tyne
NE1 4LP
United Kingdom

Trial participating centre

University College Hospital
London
NW1 2BU
United Kingdom

Trial participating centre

St. Mary's Hospital, Paddington
London
W2 1NY
United Kingdom

Trial participating centre

Royal London Hospital
London
E1 1BB
United Kingdom

Trial participating centre

University College London Hospital (UCLH)
London
NW1 2BU
United Kingdom

Trial participating centre

St. Thomas' Hospital
London
SE1 7EH
United Kingdom

Trial participating centre

Queen Charlotte's Hospital
London
W12 0HS
United Kingdom

Trial participating centre

Chelsea and Westminster Hospital
London
SW10 9NH
United Kingdom

Trial participating centre

St James’s University Hospital
Leeds
LS9 7TF
United Kingdom

Trial participating centre

Whipps Cross University Hospital
London
E11 1NR
United Kingdom

Trial participating centre

North Manchester General Hospital
Manchester
M8 5RB
United Kingdom

Trial participating centre

Royal Bolton Hospital
Bolton
BL4 0JR
United Kingdom

Trial participating centre

St Mary’s Hospital
Manchester
M13 9WL
United Kingdom

Trial participating centre

Queen Margaret Hospital
Dunfermline
KY12 0SU
United Kingdom

Trial participating centre

Heartlands Hospital
Birmingham
B9 5SS
United Kingdom

Trial participating centre

Victoria Hospital
Blackpool
FY3 8NR
United Kingdom

Trial participating centre

Kettering General Hospital
Kettering
NN16 8UZ
United Kingdom

Trial participating centre

University Hospital Coventry
Coventry
CV2 2DX
United Kingdom

Trial participating centre

Burnley General Hospital
Burnley
BB10 2PQ
United Kingdom

Trial participating centre

Royal Blackburn Hospital
Blackburn
BB2 3HH
United Kingdom

Trial participating centre

West Middlesex University Hospital
Isleworth
TW7 6AF
United Kingdom

Trial participating centre

Newham University Hospital
London
E13 8SL
United Kingdom

Trial participating centre

Queen's Medical Centre
Nottingham
NG7 2UH
United Kingdom

Trial participating centre

Nottingham City Hospital
Nottingham
NG5 1PB
United Kingdom

Trial participating centre

Liverpool Women’s Hospital
Liverpool
L8 7SS
United Kingdom

Trial participating centre

Sunderland Royal Hospital
Sunderland
SR4 7TP
United Kingdom

Trial participating centre

Birmingham City Hospital
Birmingham
B18 7QH
United Kingdom

Trial participating centre

Kingston Hospital
Kingston upon Thames
KT2 7QB
United Kingdom

Trial participating centre

Royal Preston Hospital
Preston
PR2 9HT
United Kingdom

Trial participating centre

St Michael’s Hospital
Bristol
BS2 8EG
United Kingdom

Trial participating centre

Princess Royal Hospital
Telford
TF1 6TF
United Kingdom

Trial participating centre

Queen’s Hospital
Romford
RM7 0AG
United Kingdom

Trial participating centre

Leicester Royal Infirmary
Leicester
LE1 5WW
United Kingdom

Trial participating centre

St Richard’s Hospital
Chichester
PO19 6SE
United Kingdom

Trial participating centre

Nevill Hall Hospital
Abergavenny
NP7 7EG
United Kingdom

Trial participating centre

Royal Gwent Hospital
Newport
NP20 2UB
United Kingdom

Trial participating centre

New Cross Hospital
Wolverhampton
WV10 0QP
United Kingdom

Trial participating centre

Dewsbury Hospital
Dewsbury
WF13 4HS
United Kingdom

Trial participating centre

Pinderfields Hospital
Wakefield
WF1 4DG
United Kingdom

Trial participating centre

York Hospital
York
YO31 8HE
United Kingdom

Trial participating centre

North Devon District Hospital
Barnstaple
EX31 4JB
United Kingdom

Trial participating centre

Warrington Hospital
Warrington
WA5 1QG
United Kingdom

Trial participating centre

Singleton Hospital
Swansea
SA2 8QA
United Kingdom

Trial participating centre

Bedford Hospital
Bedford
MK42 9DJ
United Kingdom

Trial participating centre

Broomfield Hospital
Chelmsford
CM1 7ET
United Kingdom

Trial participating centre

Princess Alexandra Hospital
Harlow
CM20 1QX
United Kingdom

Trial participating centre

Milton Keynes Hospital
Milton Keynes
MK6 5LD
United Kingdom

Trial participating centre

Aberdeen Maternity Hospital
Aberdeen
AB25 2ZL
United Kingdom

Trial participating centre

Torbay Hospital
Torbay
TQ2 7AA
United Kingdom

Trial participating centre

University Hospital Lewisham
Lewisham
SE13 6LH
United Kingdom

Trial participating centre

Queen Elizabeth Hospital, Woolwich
Woolwich
SE18 4QH
United Kingdom

Trial participating centre

Worcestershire Royal Hospital
Worcester
WR5 1DD
United Kingdom

Trial participating centre

Epsom Hospital
Epsom
KT18 7EG
United Kingdom

Trial participating centre

St Helier Hospital
Carshalton
SM5 1AA
United Kingdom

Trial participating centre

Luton and Dunstable University Hospital
Luton
LU4 0DZ
United Kingdom

Trial participating centre

Wrexham Maelor Hospital
Wrexham
LL13 7TD
United Kingdom

Trial participating centre

Ysbyty Glan Clwyd
Rhyl
LL18 5UL
United Kingdom

Trial participating centre

Ysbyty Gwynedd
Bangor
LL57 2PW
United Kingdom

Trial participating centre

Queen Alexandra Hospital
Portsmouth
PO6 3LY
United Kingdom

Sponsor information

Organisation

Birmingham Women’s Hospital

Sponsor details

Birmingham Women’s NHS Foundation Trust
Norton Court
Mindelsohn Way
Edgbaston
Birmingham
B15 2TG
United Kingdom

Sponsor type

Hospital/treatment centre

Website

http://www.bwnft.nhs.uk/research-developments

Funders

Funder type

Government

Funder name

Health Technology Assessment Programme

Alternative name(s)

NIHR Health Technology Assessment Programme, HTA

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

A meeting will be held after the end of the study to allow discussion of the main results among the collaborators prior to publication. The success of the study depends entirely on the wholehearted collaboration of a large number of doctors, nurses and others. For this reason, chief credit for the main results will be given not to the committees or central organisers but to all those who have collaborated in the study. Centres will be permitted to publish data obtained from participants in the C-STICH trial that use trial outcome measures but do not relate to the trial randomised evaluation and hypothesis.

IPD sharing statement
The datasets generated during and/or analysed during the current study will be stored on a secure serve at Birmingham Clinical Trials Unit, with ethics and consent.

Intention to publish date

31/10/2019

Participant level data

Stored in repository

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

22/09/2017: The following changes were made to the trial record: 1. The recruitment end date was changed from 01/04/2016 to 31/01/2018. 2. The overall trial end date was changed from 01/05/2018 to 01/10/2018. 07/06/2017: The following changes were made to the trial record: 1. The overall trial end date was changed from 01/03/2018 to 01/05/2018. 2. The sponsor was changed from University of Birmingham to Birmingham Women’s Hospital. 11/04/2016: Ethics approval information added