Carbetocin Versus Syntometrine for the Third Stage of Labour

Carbetocin Versus Syntometrine for the Third Stage of Labour Following Vaginal Delivery - A Double-blind Randomised Trial

Intramuscular carbetocin is as effective as intramuscular syntometrine for the prevention of postpartum haemorrhage

Study Overview

• Status: Completed
• Conditions: Postpartum Haemorrhage
• Intervention / Treatment: Drug: Syntommetrine and Carbetocin; Drug: Syntommetrine and Carbetocin

Detailed Description

Postpartum haemorrhage(PPH)or excessive bleeding at or after childbirth is a potentially life threatening complication and is one of the major contributors to maternal mortality and morbidity worldwide (Lewis 2001).Among the various agents that have been studied in addition to the routine oxytocin and syntometrine (which has adverse effects),oxytocin agonist (carbetocin) appears to be the most promising for this indication(Chong 2004).

Carbetocin is a licensed medication for the use of prevention of postpartum haemorrhage in Singapore and many other countries. It is a long-acting synthetic octapeptide analogue of oxytocin with agonist properties.The clinical and pharmacological properties of carbetocin are similar to those of naturally occurring oxytocin. Like oxytocin, carbetocin binds to oxytocin receptors present on the smooth musculature of the uterus, resulting in rhythmic contractions of the uterus, increased frequency of existing contractions, and increased uterine tone. In pharmacokinetic studies, intravenous injections of carbetocin produced tetanic uterine contractions within two minutes, lasting six minutes, followed by rhythmic contractions for a further hour.Intramuscular injection produced tetanic contractions in less than two minutes, lasting about 11 minutes, and followed by rhythmic contractions for an additional two hours. The prolonged duration of activity after intramuscular compared with the intravenous carbetocin was significant(Hunter 1992). In comparison to oxytocin, carbetocin induces a prolonged uterine response when administered postpartum, in terms of both amplitude and frequency of contractions.

The potential advantage of intramuscular carbetocin over intramuscular oxytocin is its longer duration of action. Its relative lack of gastrointestinal and cardiovascular side-effects should also prove advantageous compared to syntometrine and other ergot alkaloids.

• Study Type: Interventional
• Enrollment (Anticipated): 720
• Phase: Phase 4

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 119074
    • National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Any pregnant woman expected to deliver vaginally
2. Age more than 21 if not married
3. Ability to provide informed consent

Exclusion Criteria:

1. Multiple pregnancy
2. Patients with other risk factors for postpartum haemorrhage
3. Patients planning to have an elective caesarean section
4. History of vascular disease such as coronary artery disease
5. History of hypertension requiring treatment within the last 2 years
6. History of hepatic or renal disease
7. Known or suspected coagulopathy
8. History of hypersensitivity to oxytocin or carbetocin
9. Any condition where the use of syntometrine/carbetocin is contraindicated

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Primi	Drug: Syntommetrine and Carbetocin; Syntommetrine 1ml and Carbetocin 100microgram; Drug: Syntommetrine and Carbetocin; Syntommetrine 1ml and Carbetocin 100micgrams
Active Comparator: Multi	Drug: Syntommetrine and Carbetocin; Syntommetrine 1ml and Carbetocin 100microgram; Drug: Syntommetrine and Carbetocin; Syntommetrine 1ml and Carbetocin 100micgrams

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
1. Postpartum haemorrhage (less than or equal to 500 ml) 2. Postpartum haemorrhage (less than or equal to 1000ml) 3. Use of additional uterotonic therapy	Within 2 hours after delivery

Secondary Outcome Measures

Outcome Measure	Time Frame
1. Adverse effects with the intervention which include headache, nausea, vomiting, elevation of blood pressure and retained placenta 2. Cost effectiveness analysis of the intervention	Within 2 hours after delivery

Collaborators and Investigators

• Sponsor: National University Hospital, Singapore
• Collaborators: National Healthcare Group, Singapore
• Investigators: Principal Investigator: Su Lin Lin, MBBS, National University Hospital, Singapore

Study record dates

Study Major Dates

• Study Start: November 1, 2006
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): July 1, 2009

Study Registration Dates

• First Submitted: July 9, 2007
• First Submitted That Met QC Criteria: July 10, 2007
• First Posted (Estimate): July 11, 2007

Study Record Updates

• Last Update Posted (Estimate): September 21, 2009
• Last Update Submitted That Met QC Criteria: September 18, 2009
• Last Verified: September 1, 2009

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Pregnancy Complications; Obstetric Labor Complications; Puerperal Disorders; Uterine Hemorrhage; Hemorrhage; Postpartum Hemorrhage; Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Oxytocin; Carbetocin
• Other Study ID Numbers: DSRB Ref: D/04/209; NHG-SIG/07059