Intramuscular Oxytocics: A Randomised Control Trial

NCT02216383 | Completed Phase 3 DMC

• 2 other identifiers: 33442014-001948-37
• Study Type: interventional
• Target: 5,798
• Locations: 1 country
• Sites: 5

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.

Conditions

Post Partum Haemorrhage

Keywords

Post partum haemorrhage; Active Management of Third Stage of Labour; Carbetocin; Syntocinon; Syntometrine; Birth experience; Labour

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (12)

• Estimated volume of blood loss at delivery

  Within 24 hours of delivery

• Transfusion of blood products (type and number of units given)

  From delivery until transfer from Labour Ward, within an expected average of 6 hours.

• Manual removal of placenta in theatre

  From delivery until transfer from Labour Ward

• Requirement for surgical intervention to manage PPH

  From delivery until transfer from Labour Ward, within an expected average of 2 days

• Maternal hypertension

  First two postnatal hours following administration of study drug

Study Arms (3)

Carbetocin

EXPERIMENTAL

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

Drug: Carbetocin

Syntocinon

ACTIVE COMPARATOR

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

Drug: Syntocinon

Syntometrine

ACTIVE COMPARATOR

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

Drug: Syntometrine

Interventions

Carbetocin 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.

Also known as: Pabal

Carbetocin

Syntocinon 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.

Also known as: Oxytocin

Syntocinon

Syntometrine 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.

Also known as: Syntometrine 500 micrograms/5 IU Solution for Injection

Syntometrine

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥18 years of age at time of delivery
• Singleton pregnancy
• Vaginal birth (spontaneous and instrumental)
• \>24 weeks gestation

You may not qualify if:

• 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

Sponsors & Collaborators

• North Bristol NHS Trust: lead
• Ferring Pharmaceuticals: collaborator
• University of Bristol: collaborator
• University of the West of England: collaborator
• Royal United Hospital Bath NHS Trust: collaborator
• Gloucestershire Hospitals NHS Foundation Trust: collaborator
• University Hospitals Bristol and Weston NHS Foundation Trust: collaborator

Study Sites (5)

North Bristol NHS Trust

Bristol, Avon, BS10 5NB, United Kingdom

Location

Gloucestershire Hospitals NHS Trust

Gloucester, Gloucestershire, GL1 3NN, United Kingdom

Location

Royal United Hospital NHS Trust

Bath, Somerset, BA1 3NG, United Kingdom

Location

Nottingham University Hospitals NHS Trust

Nottingham, United Kingdom

Location

Great Western Hospital

Swindon, SN3 6BB, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 30606246 DERIVED

MeSH Terms

Conditions

Postpartum Hemorrhage

Interventions

carbetocin; Oxytocin; syntometrine; Injections

Condition Hierarchy (Ancestors)

Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Puerperal Disorders; Uterine Hemorrhage; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Tim Draycott, BMBS

  North Bristol NHS Trust/University of Bristol

  STUDY DIRECTOR

• Helen van der Nelson, BMBS

  North Bristol NHS Trust/University of Bristol

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2014
• First Posted: August 15, 2014
• Study Start: February 1, 2015
• Primary Completion: August 31, 2018
• Study Completion: October 30, 2018
• Last Updated: November 14, 2018

Record last verified: 2018-08

Locations

GB (5)