Intramuscular Oxytocics: A Randomised Control Trial

Post Partum Haemorrhage Clinical Trial

— IMox  

Official title:

Intramuscular Oxytocics: A Randomised Control Trial of Intramuscular Carbetocin, Syntocinon and Syntometrine for the Third Stage of Labour Following Vaginal Birth

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02216383
• Other study ID #: 3344
• Secondary ID: 2014-001948-37
• Status: Completed
• Phase: Phase 3
• Start date: February 2015
• Est. completion date: October 30, 2018

Study information

• Verified date: August 2018
• Source: North Bristol NHS Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A quarter of all pregnancy and child-birth related deaths are due to excessive bleeding after the birth, "post-partum haemorrhage" (PPH). In the UK, PPH affects approx 10% of new mothers. PPH can be frightening for women and cause them to need additional treatments prolonging their hospital stay.

Commonly PPH is caused by an inadequately contracted womb after childbirth. Giving the mother an injection of "uterotonic" medicine following the birth of their baby can prevent this. It reduces the risk of PPH by 66%.

In the UK, the two medicines most commonly used are Syntocinon and Syntometrine. Syntometrine is longer acting, but a published review of trials concluded that Syntometrine is no better at preventing severe blood loss. Syntometrine is associated with more side effects including nausea, vomiting, and high blood pressure, and has been linked with rare, but fatal, cases of stroke. All guidelines therefore recommend Syntocinon for preventing PPH.Following a telephone survey of all maternity units in the UK, 71.4% of units still routinely use Syntometrine.

Carbetocin is a newer medicine, already widely used after caesarean section, but not yet after vaginal birth. Other studies have shown that Carbetocin is slightly better at preventing bleeding after birth when compared to Syntometrine, has fewer side effects than Syntometrine, and that it may be just as good as Syntocinon at preventing PPH. No studies have directly compared all three medicines or compared their overall cost; information vital to the NHS.

Investigators propose a trial of 5712 women over 13 months, in four maternity units to compare the effectiveness, side effects and cost of Syntocinon, Syntometrine and Carbetocin, for women having a vaginal birth.

Women will be randomly allocated to receive one of these drugs. Women and staff will not know which drug they receive. Staff will collect data such as the number of extra drugs and treatments needed and the volume of blood lost. Women will be asked to complete a side effects questionnaire. Investigators will perform an analysis of cost effectiveness once all results are available.

Aim: To directly compare the effectiveness, side effects and cost of Syntocinon, Syntometrine and Carbetocin given intramuscularly to prevent PPH in the 3rd stage of labour.

Description:

BACKGROUND Around a quarter of all global pregnancy and child-birth related deaths are due to excessive bleeding after the birth of the baby and placenta, or "post-partum haemorrhage" (PPH). In the UK, PPH affects approximately 10% of new mothers. PPH can be extremely frightening for women and can cause them to need additional treatments including blood transfusion and removal of the womb as well as prolonging their hospital stay.

The most common cause of PPH is an inadequately contracted womb after childbirth. Giving the mother an injection of "uterotonic" medicine following the birth of their baby can prevent this. It reduces the risk of PPH by 66% and this should routinely be offered to all labouring women.

In the UK, the two medicines most commonly used for this purpose are Syntocinon and Syntometrine. Both mimic natural hormones. Syntometrine is longer acting, but a published review of trials comparing these two medicines concluded that Syntometrine is no better at preventing severe blood loss. Syntometrine is associated with more side effects including nausea, vomiting, and high blood pressure, and has been linked with rare, but fatal, cases of stroke. All guidelines therefore recommend Syntocinon for preventing PPH.

Our group conducted a telephone survey of all maternity units in the UK, and found that 71.4% of units still routinely use Syntometrine. Investigators estimate that 40,000-70,000 women per year are experiencing distressing nausea and vomiting in the emotionally important first few hours following childbirth. These women are also receiving a medicine with the potential to cause dangerous high blood pressure.

Carbetocin is a newer medicine, already widely used after caesarean section, but not yet after vaginal birth. Other studies have shown that Carbetocin is slightly better at preventing bleeding after birth when compared to Syntometrine, that it has fewer side effects than Syntometrine, and that it may be just as good as Syntocinon at preventing PPH. No studies have directly compared all three medicines or compared their overall cost; information vital to the NHS.

METHOD Investigators propose a trial of 5712 women over 13 months, in four maternity units in the South-West to compare the effectiveness, side effects and cost of Syntocinon, Syntometrine and Carbetocin, for women having a vaginal birth.

Women will be randomly allocated to receive one of these drugs. Women and staff will not know which drug they receive, so as not to influence the results collected. Staff will collect data such as the number of extra drugs and treatments needed and the volume of blood lost. Women will be asked to complete a side effects questionnaire. Investigators will perform an analysis of cost effectiveness once all results are available.

AIMS To directly compare the effectiveness, side effects and cost of Syntocinon, Syntometrine and Carbetocin given intramuscularly to prevent PPH in the 3rd stage of labour.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5798
• Est. completion date: October 30, 2018
• Est. primary completion date: August 31, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• =18 years of age at time of delivery

• Singleton pregnancy

• Vaginal birth (spontaneous and instrumental)

• >24 weeks gestation

Exclusion Criteria:

• Significant APH (>50ml) or suspected or proven placenta abruption

• Maternal coagulation disorder

• Intrauterine fetal death

• Patients who would decline blood products if required

• Known or suspected hypertensive disorders, including pre-eclampsia, pregnancy induced hypertension, essential hypertension (even if blood pressure well controlled)

• Hypertension in labour, or patients who have not had their blood pressure checked in labour

• Patients with peripheral, hepatic or cardiac disease

• Patients with an allergy or hypersensitivity to any of the active ingredients in Carbetocin, Syntometrine or Syntocinon

• Epilepsy

Related Conditions & MeSH terms

• Hemorrhage
• Post Partum Haemorrhage
• Postpartum Hemorrhage

Intervention

Drug:
• Carbetocin
The intervention is the administration of one dose of study drug to the recruited patient at the time of delivery. Carbetocin, listed here, is one of the of the three study drugs.
• Syntocinon
The intervention is the administration of one dose of study drug to the recruited patient at the time of delivery. Syntocinon, listed here, is one of the of the three study drugs.
• Syntometrine
The intervention is the administration of one dose of study drug to the recruited patient at the time of delivery. Syntometrine, listed here, is one of the of the three study drugs.

Locations

Country	Name	City	State
United Kingdom	Royal United Hospital NHS Trust	Bath	Somerset
United Kingdom	North Bristol NHS Trust	Bristol	Avon
United Kingdom	Gloucestershire Hospitals NHS Trust	Gloucester	Gloucestershire
United Kingdom	Nottingham University Hospitals NHS Trust	Nottingham
United Kingdom	Great Western Hospital	Swindon

Sponsors (7)

Lead Sponsor	Collaborator
North Bristol NHS Trust	Ferring Pharmaceuticals, Gloucestershire Hospitals NHS Foundation Trust, Royal United Hospital Bath NHS Trust, University Hospitals Bristol NHS Foundation Trust, University of Bristol, University of the West of England

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Requirement for additional uterotonic drugs within 24 hours of birth	Proportion of patients requiring additional uterotonic drugs after administration of study drug	From administration of prophylactic uterotonic agent to discharge from labour ward, within an expected average of 6 hours.
Secondary	Estimated volume of blood loss at delivery	Estimated volume of blood loss at delivery	Within 24 hours of delivery
Secondary	Transfusion of blood products (type and number of units given)	Number of units of blood transfused, or volume of own blood returned to patient if intraoperative cell salvage used	From delivery until transfer from Labour Ward, within an expected average of 6 hours.
Secondary	Manual removal of placenta in theatre	The requirement for the placenta to be removed in theatre	From delivery until transfer from Labour Ward
Secondary	Requirement for surgical intervention to manage PPH	As a result of significant PPH a surgical intervention was required to manage the PPH	From delivery until transfer from Labour Ward, within an expected average of 2 days
Secondary	Maternal hypertension	Hypertension	First two postnatal hours following administration of study drug
Secondary	Maternal hypotension	BP <90/60	In first two postnatal hours
Secondary	Maternally-reported health-related quality of life	health-related quality of life reported by mother	24 hours after delivery and 14 days after delivery
Secondary	Abdominal pain in the first two postnatal hours, recorded in Case Report Form (CRF) by midwife	Patient reported secondary outcome	First 2 post natal hours
Secondary	Post-partum vomiting	Patient reported secondary outcome	First 2 post natal hours
Secondary	Need for anti-emetic	Patient reported secondary outcome; By definition, labour starts when the patient is at least 3-4cm dilated with regular, painful contractions.	First 2 post natal hours
Secondary	Headache	Patient reported secondary outcome	First two post natal hours
Secondary	Maternal experience of side effects	Captured using maternal side effects questionnaire	In first two post natal hours