Intramuscular Oxytocics: A Randomised Control Trial (IMox)

NHS Trust

Status and phase: Completed; Phase 3

Conditions: Post Partum Haemorrhage

Treatments: Drug: Syntometrine; Drug: Carbetocin; Drug: Syntocinon

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02216383

2014-001948-37 (EudraCT Number)

3344

Details and patient eligibility

About

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.

Full 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.

Enrollment: 5,798 patients

Sex: Female

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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5,798 participants in 3 patient groups

Carbetocin

Experimental group

Description:

One dose of 100 micrograms intramuscular Carbetocin given for active management of the third stage of labour, immediately after the birth of the baby

Treatment:

Drug: Carbetocin

Syntocinon

Active Comparator group

Description:

One dose of 10 International Units intramuscular Syntocinon given for active management of the third stage of labour, immediately after the birth of the baby

Treatment:

Drug: Syntocinon

Syntometrine

Active Comparator group

Description:

One dose of 500micrograms/5 International Units intramuscular Syntometrine given for active management of the third stage of labour, immediately after the birth of the baby

Treatment:

Drug: Syntometrine