Clinical trial NCT02216383: Intramuscular Oxytocics: A Randomised Control Trial
Official title: Intramuscular Oxytocics: A Randomised Control Trial of Intramuscular Carbetocin, Syntocinon and Syntometrine for the Third Stage of Labour Following Vaginal Birth
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Post Partum Haemorrhage
Keywords: Post partum haemorrhage
Active Management of Third Stage of Labour
Carbetocin
Syntocinon
Syntometrine
Birth experience
Labour
Lead sponsor: North Bristol NHS Trust
Sponsor class: OTHER
Collaborators: name: Ferring Pharmaceuticals
name: University of Bristol
name: University of the West of England
name: Royal United Hospital Bath NHS Trust
name: Gloucestershire Hospitals NHS Foundation Trust
name: University Hospitals Bristol and Weston NHS Foundation Trust
First posted: 2014-08-15
Enrollment: 5798
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Requirement for additional uterotonic drugs within 24 hours of birth
timeFrame: From administration of prophylactic uterotonic agent to discharge from labour ward, within an expected average of 6 hours.
Secondary outcomes:
measure: Estimated volume of blood loss at delivery
timeFrame: Within 24 hours of delivery
measure: Transfusion of blood products (type and number of units given)
timeFrame: From delivery until transfer from Labour Ward, within an expected average of 6 hours.
measure: Manual removal of placenta in theatre
timeFrame: From delivery until transfer from Labour Ward
measure: Requirement for surgical intervention to manage PPH
timeFrame: From delivery until transfer from Labour Ward, within an expected average of 2 days
measure: Maternal hypertension
timeFrame: First two postnatal hours following administration of study drug
measure: Maternal hypotension
timeFrame: In first two postnatal hours
measure: Maternally-reported health-related quality of life
timeFrame: 24 hours after delivery and 14 days after delivery
measure: Abdominal pain in the first two postnatal hours, recorded in Case Report Form (CRF) by midwife
timeFrame: First 2 post natal hours
measure: Post-partum vomiting
timeFrame: First 2 post natal hours
measure: Need for anti-emetic
timeFrame: First 2 post natal hours
measure: Headache
timeFrame: First two post natal hours
measure: Maternal experience of side effects
timeFrame: In first two post natal hours
Other outcomes:
Locations:
city: Bristol
country: United Kingdom
facility: North Bristol NHS Trust
state: Avon
city: Gloucester
country: United Kingdom
facility: Gloucestershire Hospitals NHS Trust
state: Gloucestershire
city: Bath
country: United Kingdom
facility: Royal United Hospital NHS Trust
state: Somerset
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
city: Swindon
country: United Kingdom
facility: Great Western Hospital
Study officials:
affiliation: North Bristol NHS Trust/University of Bristol
name: Tim Draycott, BMBS
role: STUDY_DIRECTOR
affiliation: North Bristol NHS Trust/University of Bristol
name: Helen van der Nelson, BMBS
role: STUDY_CHAIR
References:
citation: van der Nelson H, O'Brien S, Lenguerrand E, Marques E, Alvarez M, Mayer M, Burnard S, Siassakos D, Draycott T. Intramuscular oxytocin versus oxytocin/ergometrine versus carbetocin for prevention of primary postpartum haemorrhage after vaginal birth: study protocol for a randomised controlled trial (the IMox study). Trials. 2019 Jan 3;20(1):4. doi: 10.1186/s13063-018-3109-2.