Intramuscular Oxytocics: A Randomised Control Trial

NCT ID: NCT02216383

Last Updated: 2018-11-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 5798 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-02-28
• Study Completion Date: 2018-10-30

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.

Conditions

Post Partum Haemorrhage

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Carbetocin

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

Group Type: EXPERIMENTAL

Carbetocin

Intervention Type: DRUG

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

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

Group Type: ACTIVE_COMPARATOR

Syntocinon

Intervention Type: DRUG

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

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

Group Type: ACTIVE_COMPARATOR

Syntometrine

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Other Intervention Names

Pabal; Oxytocin; Syntometrine 500 micrograms/5 IU Solution for Injection

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Ferring Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

University of Bristol

OTHER

Sponsor Role: collaborator

University of the West of England

OTHER

Sponsor Role: collaborator

Royal United Hospital Bath NHS Trust

OTHER

Sponsor Role: collaborator

Gloucestershire Hospitals NHS Foundation Trust

OTHER

Sponsor Role: collaborator

University Hospitals Bristol and Weston NHS Foundation Trust

OTHER

Sponsor Role: collaborator

North Bristol NHS Trust

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tim Draycott, BMBS

Role: STUDY_DIRECTOR

North Bristol NHS Trust/University of Bristol

Helen van der Nelson, BMBS

Role: STUDY_CHAIR

North Bristol NHS Trust/University of Bristol

Locations

North Bristol NHS Trust

Bristol, Avon, United Kingdom

Gloucestershire Hospitals NHS Trust

Gloucester, Gloucestershire, United Kingdom

Royal United Hospital NHS Trust

Bath, Somerset, United Kingdom

Nottingham University Hospitals NHS Trust

Nottingham, , United Kingdom

Great Western Hospital

Swindon, , United Kingdom

Countries

United Kingdom

References

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.

Reference Type: DERIVED

PMID: 30606246 (View on PubMed)

Other Identifiers

2014-001948-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

3344

Identifier Type: -

Identifier Source: org_study_id