High Or low dose Syntocinon® for delay in labour

ISRCTN	ISRCTN99841044
DOI	https://doi.org/10.1186/ISRCTN99841044
Clinical Trials Information System (CTIS)	2015-005537-50
Protocol serial number	v2.0; HTA Project: 14/140/44
Sponsor	Birmingham Womens NHS Foundation Trust
Funder	Health Technology Assessment Programme

Submission date: 11/07/2016
Registration date: 03/08/2016
Last edited: 20/09/2023

Recruitment status: No longer recruiting
Overall study status: Completed
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
It is not currently known what the best care for first time mothers with delayed progress in the first stage of labour is. This topic is a research priority for the Royal College of Obstetricians and Gynaecologists. Delayed labour is relatively common, affecting between 11- 30% (equivalent to between one and three in ten) of first time mothers. The only recommended treatment is artificial oxytocin (Syntocinon®) which is given intravenously (through the vein) to stimulate contractions. A standard regimen (concentration and rate of administration) is recommended by NICE Guidelines 2014 and is widely used in the UK. Information from studies looking at different dose regimens of Syntocinon ® for delayed labour suggest that a high dose regimen may reduce the chance of Caesarean section but the available evidence is not conclusive. Syntocinon ® may cause the uterus to contract too much and the baby to become distressed so both mother and baby are carefully monitored and the dose adjusted in relation to the number of contractions and how the baby is. Research shows currently around 32% (equivalent to about three in ten) of the women who need Syntocinon® for delayed labour have an unplanned Caesarean section , which is related to a longer hospital stay, higher risk of infection, bleeding and blood clots and to increase risk of Caesarean section being required in future pregnancies. By reducing the number of Caesarean sections, these risks can also be reduced. A reduction in the Caesarean section rate of 5-8% (equivalent to nearly one in ten) in these women could save the NHS nearly £1M per year, as well as possible annual savings of £2.6M from the impact of avoiding Caesarean section in future pregnancies. The study is looking at whether treatment with a high dose of Syntocinon® reduces the need for Caesarean section in women with delayed labour.

Who can participate?
Women having their first baby and confirmed as being in delayed labour.

What does the study involve?
Participants are randomly allocated to one of two groups. Those in group 1 are treated with the standard dose of oxytocin. Those in group 2 are treated with a high dose of oxytocin, which is double the concentration of the standard dose. All participants from both groups are followed to see, for example, whether they have to have a caesarean section, have an epidural during the labour, how long each of the three stages of labour takes and how long the birth takes altogether.

What are the possible benefits and risks of participating?
Syntocinon ® may cause the uterus to contract too much and the baby to become distressed so both mother and baby are carefully monitored and the dose adjusted in relation to the number of contractions and how the baby is.

Where is the study run from?
Birmingham Womens NHS Foundation Trust (UK)

When is the study starting and how long is it expected to run for?
March 2016 to May 2019

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

Who is the main contact?
Dr Sara Kenyon
HOLDS@trials.bham.ac.uk

Contact information

Dr Sara Kenyon
Public

University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom

Phone	0121 415 8298
Email	HOLDS@trials.bham.ac.uk

Study information

Primary study design	Interventional
Study design	Multicentre pragmatic randomized double-blind controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	High Or Low Dose Syntocinon® for delay in labour: the HOLDS trial
Study acronym	HOLDS
Study objectives	HOLDS will provide robust evidence of clinical effectiveness of a high dose compared to the current standard dose regimen of oxytocin in reducing the need for Caesarean section (CS) for nulliparous women with confirmed delay in the first stage of labour.
Ethics approval(s)	West Midlands - Edgbaston Research Ethics Committee, 24/02/2016, ref: 16/WM/0014
Health condition(s) or problem(s) studied	Nulliparous women with a singleton cephalic pregnancy at term (37-42 weeks gestation) with confirmed delay in labour and ruptured membranes as defined by NICE Intrapartum Care Guidelines for whom the clinical decision has been made to prescribe Syntocinon for augmentation of labour.
Intervention	HOLDS is a double- blinded randomised controlled trial which will compare the standard dose regimen of oxytocin with a high dose regimen. NICE guidance recommends a standard dose regimen of oxytocin (2mU/min increasing every 30 minutes to a maximum 32mU/min). The comparator is high dose regimen (4mU/min increasing every 30 minutes to a maximum of 64mU/min). The high dose regimen ( i.e. double the concentration) has a higher starting dose, earlier attainment of conventional maximum doses (at 2 hours rather than over 4 hours) and the possible use of higher maximum doses of oxytocin compared to the standard regimen. Once delay in labour is confirmed women will be randomised to the standard dose will receive a solution containing 2 x 5iu ampoules in 50mls or 500mls and those to the high dose a solution containing 2 x 10iu in 50 mls or 500mls. Ampoules are manufactured as 5 and 10 iu and these regimens have been selected to enable the trial to be double-blinded. Intervention will last for the remainder of the first stage and until completion of the second stage of labour. Data will be collected by the research midwife through CRFs (i.e., labour, birth and discharge and a neonatal CRFs) from clinical data routinely recorded. Data collection will start after the participant has given consent and end at discharge from hospital.
Intervention type	Drug
Phase	Phase III
Drug / device / biological / vaccine name(s)	Syntocinon (Oxytocin)
Primary outcome measure(s)	Incidence of caesarean section, data taken from medical notes
Key secondary outcome measure(s)	1. Incidence of epidural use during labour 2. Duration of first, second and third stages of labour 3. Time to birth from randomisation 4. Prevalence of mode of birth (spontaneous vaginal birth (SVB), instrumental or caesarean section) 5. Degree of perineal trauma (first, second, third and fourth) 6. Reason for caesarean section and decision to delivery interval for CS 7. Confirmed urinary retention requiring catheterisation and pulmonary oedema 8. Tachysystole (uterine contractions greater than 5 in 10 mins for 20 minutes) requiring reduction in oxytocin and/or tocolysis 9. Hyperstimulation (uterine contractions greater than 5 in 10 mins for 20 minutes resulting in non-ressurring or abnormal fetal heart rate) 10. Fetal blood sampling (FBS) during labour or significant STAN event (for those Units that use ST waveform analysis for intrapartum fetal monitoring) 11. Abnormal cardiotocogram leading to immediate birth without fetal blood sample 12. Incidence of maternal morbidity (anaphylaxis, pulmonary oedema, postpartum haemorrhage, shoulder dystocia, chorioamnioitis, uterine rupture/hysterectomy) 13. Active management of third stage of labour 14. Length of time after birth in hospital [days] 15. Admission to HDU/ITU 16. Maternal death 17. Time from randomisation to commencement of allocation 18. Total oxytocin dose 19. Time to maximum oxytocin rate 20. Maximum oxytocin dose reached 21. Gender and birthweight of neonate 22. Apgar score at 5 minutes 23. Arterial cord blood gases when collected 24. Breastfeeding rates on discharge from hospital 25. Length of time after birth in hospital [days] 26. Incidence of need to resuscitate neonate 27. Reason for neonatal review on ward (excluding routine baby check) 28. Reason for admission to neonatal unit (NNU) and level of care received (level 1,2,3) including intensive care 29. Duration of respiratory support for neonate 30. Number of days to full oral feeds 31. Incidence of seizures of neonate 32. Incidence of neonatal encephalopathy ( SARNAT grade) 33. Incidence of therapeutic hypothermia (cooling) of neonate required 34. Incidence of intrapartum still birth 35. Incidence of early neonatal death (within seven days of birth) All data taken from medical notes other than outcome 18, where the data is recorded directly onto the Clinical Records Form.
Completion date	31/05/2019

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Female
Target sample size at registration	1500
Key inclusion criteria	1. Nulliparous women with singleton cephalic pregnancy at term (37-42 weeks gestation) 2. Confirmed delay in labour and ruptured membranes for whom the clinical decision has been made to prescribe Syntocinon for augmentation of labour According to NICE guidance [NICE 2014], labour is established when there are regular painful contractions and progressive cervical dilation from 4 cm. Delay is suspected when cervical dilation of < 2 cm in 4 hours occurs once labour is established. Delay is confirmed when progress of <1 cm in 2 hours is found on repeat vaginal examination.
Key exclusion criteria	1. Multiparous women 2. Nulliparous women who: 2.1. Are undergoing induction of labour 2.2. Have a BMI >40 at booking 2.3. Have a multiple pregnancy 2.4. Have existing cardiac disease, bleeding disorders, diabetes (either pre-existing or gestational), previous uterine surgery 2.5. Have had significant antepartum haemorrhage 2.6. Are under 16 years of age 2.7. Have a known contra-indication to oxytocin therapy as listed in the Summary of marketing Product Characteristics
Date of first enrolment	01/03/2017
Date of final enrolment	31/08/2018

Locations

Countries of recruitment

United Kingdom
England
Wales

Study participating centres

Birmingham Womens NHS Foundation Trust

Mindelsohn Way
Edgbaston
Birmingham
B15 2TG
United Kingdom

Birmingham Women and Children`s Hospital

Steelhouse Lane
Birmingham
B4 6NH
United Kingdom

Royal Victoria Infirmary Newcastle

Queen Victoria Road
Newcastle upon Tyne
NE1 4LP
United Kingdom

St Mary’s Hospital

Oxford Road
Manchester
M13 9WL
United Kingdom

James Cook University Hospital

Marton Road
Middlesbrough
TS4 3BW
United Kingdom

University Hospital of Wales

Heath Park Way
Cardiff
CF14 4XW
United Kingdom

St Thomas’ Hospital London

Westminster Bridge Road
Lambeth
London
SE1 7EH
United Kingdom

Nottingham City Hospital

Hucknall Road
Nottingham
NG5 1PB
United Kingdom

Burnley General Hospital

Casterton Avenue
Burnley
BB10 2PQ
United Kingdom

Queens Medical Centre

Derby Road
Nottingham
NG7 2UH
United Kingdom

Sunderland Royal Hospital

Kayll Road
Sunderland
SR4 7TP
United Kingdom

Liverpool Women’s Hospital

Crown Street
Liverpool
L8 7SS
United Kingdom

West Middlesex University hospital

Twickenham Road
Isleworth
TW7 6AF
United Kingdom

Norfolk and Norwich Hospital

Colney Lane
Norwich
NR4 7UY
United Kingdom

Royal Preston

Sharoe Green Lane North
Fulwood
Preston
PR2 9HT
United Kingdom

Princess Anne Hospital

Coxford Road
Southampton
Southampton
SO16 5YA
United Kingdom

The Princess Royal Hospital, Telford

Apley Castle
Apley
Telford
TF1 6TF
United Kingdom

St James’s University Hospital Leeds

Beckett Street
Leeds
LS9 7TF
United Kingdom

Leeds General Hospital

Great George Street
Leeds
LS1 3EX
United Kingdom

Royal Cornwall Hospital

Treliske
Truro
TR1 3LQ
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Data sharing statement to be made available at a later date
IPD sharing plan	The data sharing plans for the current study are unknown and will be made available at a later date

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
HRA research summary			20/09/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

20/09/2023: A link to the HRA research summary was added.
04/09/2017: Individual patient data sharing statement has been added. The following have been added as trial participating sites: Birmingham Women and Children's Hospital, Royal Victoria Infirmary Newcastle, St Mary’s Hospital Manchester, James Cook, University Hospital of Wales, St Thomas’ Hospital London, Nottingham City Hospital, Burnley General Hospital, Queens Medical Centre Nottingham, Sunderland Royal Hospital, Liverpool Women’s Hospital, West Middlesex University Hospital, Norfolk and Norwich Hospital, Royal Preston, Princess Anne Hospital, Southampton, The Princess Royal Hospital, Telford, St James’s University Hospital Leeds, Leeds General Hospital, Royal Cornwall Hospital.