Oxytocin in Cesarean Delivery

Post Partum Hemorrhage Clinical Trial

Official title:

Comparing Oxytocin and Oxytocin-ergometrine Combinations for Increasing Uterine Tone in Cesarean Delivery: a Pharmacokinetic-pharmacodynamic Study.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01236482
• Other study ID #: oxytocined50-HMO-CTIL
• Status: Not yet recruiting
• Phase: Phase 4
• First received: September 27, 2010
• Last updated: November 5, 2010
• Start date: November 2010
• Est. completion date: May 2011

Study information

• Verified date: September 2010
• Source: Hadassah Medical Organization
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

In this study the investigators hypothesize that infused combinations of oxytocin and ergometrine will exhibit fewer cardiac and neurological side effects than equipotent infusion of oxytocin alone. In order to perform this study the investigators perform the following steps:

1. The investigators validate a quantitative measure of uterine tone as our primary endpoint.

2. The investigators use this endpoint measure in order to determine equipotential doses of different tocotonic drug regimens, based on the ED50 for each.

3. Using equipontial ratios based on the ED50, the investigators compare hemodynamic and other side effects of these tocotonic drug regimes. Plasma levels of oxytocin will be measured.

Description:

Obstetric hemorrhage is associated with severe maternal morbidityש and maternal death. The use of tocotonic drugs following delivery is routine practice as part of the active management of the third stage of labor, to increase uterine tone and reduce blood loss. However, the use of these drugs is not without side effects and complications. Oxytocin causes profound vasodilatation, hypotension and increased cardiac output and has been associated with chest pain, reduced arterial oxygen saturation and ST segment changes on ECG. Ergometrine, on the other hand, causes systemic vasoconstriction and hypertension, and reduced cardiac output. As oxytocin and ergometrine are associated with opposing hemodynamic sequelae, there is a rationale to justify the co-administration of both of these drugs in an attempt to cancel out their side effects.

No clinical studies have attempted to titrate the dose of tocotonic drugs against a quantified measure of uterine tone. As a consequence, comparisons of the hemodynamic side effects of oxytocin and other tocotonic agents (particularly ergometrine) have not been based on a knowledge of equipotential doses, making the rational comparison of side effects impossible.

In this study we hypothesize that infused combinations of oxytocin and ergometrine will exhibit fewer cardiac and neurological side effects than equipotent infusion of oxytocin alone. In order to perform this study we perform the following steps:

1) We validate a quantitative measure of uterine tone as our primary endpoint. 2) We use this endpoint measure in order to determine equipotential doses of different tocotonic drug regimens, based on the ED50 for each. 3) Using equipontial ratios based on the ED50, we compare hemodynamic and other side effects of these tocotonic drug regimes. Plasma levels of oxytocin will be measured to enable pharmacokinetic-pharmacodynamic assessments to be made.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 80
• Est. completion date: May 2011
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• 80 healthy women presenting for elective repeat cesarean delivery under regional anesthesia.

• All women are ASA class 1-2, aged 18 - 45, with body weight 60-100 kg.

Exclusion Criteria:

• Obstetric risk factors: Pre-eclampsia, abnormalities of placentation (eg placenta accrete, placenta previa), amnionitis, multiple gestation, preterm delivery (< 37 completed weeks), more than three previous cesarean deliveries, previous history of ante-partum or post-partum hemorrhage.

• Maternal medical risk factors: Chronic hypertension, cardiac disease, intracranial pathology, known allergies to oxytocin or ergometrine, autoimmune disorders, SLE, coagulation defect or anticoagulation therapy, amnionitis.

• Women asking for cord blood donations are not included in this study due to the long elapsed time between delivery and the commencement of oxytocin.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hemorrhage
• Post Partum Hemorrhage
• Postpartum Hemorrhage

Intervention

Drug:
• Oxytocin versus oxytocin-ergometrine
Group 1: Oxytocin 0.1 I.U./kg/hr (plain) Group 2: Oxytocin 0.1 I.U./kg/hr with ergometrine 2 mcg/kg/hr co-administered Infusion rates determined to achieve equipotential doses based on an earlier PKPD study

Locations

Country	Name	City	State
Israel	Hadassah Hebrew University Medical Center	Jerusalem

Sponsors (1)

Lead Sponsor	Collaborator
Hadassah Medical Organization

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Uterine tone	Uterine tone as measured by tissue durometry	Up to 30 minutes	No
Secondary	Plasma levels of oxytocin		Up to 30 minutes	No
Secondary	Subjective side effects	Headache, chest pain, shortness of breath	Up to 120 minutes	Yes