Comparison of IV Ergonovine With IM Carboprost, With Oxytocin IV, During Cesarean Section for Failure to Progress

Comparison of Intravenous Ergonovine With Intramuscular Carboprost, Both in Combination With Oxytocin Infusion, During Cesarean Section for Failure to Progress in Labor: A Double-blinded Placebo-controlled Randomized Controlled Trial

Patients having Cesarean section after they have been in labor for many hours bleed much more, in average twice as much, as compared with patients having an elective Cesarean section. The investigators believe a simple change in practice might contribute to reduce this bleeding. This study will involve the use of oxytocin (also known as syntocinon), ergonovine (also known as ergot) and carboprost (also known as hemabate). Oxytocin is routinely used to help contract the uterus and keep it contracted after the delivery of the baby and placenta, so as to reduce the amount of blood loss. Ergonovine is also given through the intravenous line, while carboprost is given as an injection in the muscle. Although they are not routinely given in every case, these are very frequently given as rescue medications to patients who fail to respond appropriately to oxytocin. This study is designed to determine if ergonovine or carboprost given in association with oxytocin, in a preventive way, after delivery of the baby and placenta, can reduce the amount of blood loss during Cesarean sections following a trial of labour.

Study Overview

• Status: Completed
• Conditions: Postpartum Hemorrhage
• Intervention / Treatment: Drug: Oxytocin; Drug: Ergot; Drug: Carboprost

Detailed Description

The objective of the investigators study is to compare the efficacy of intravenous ergonovine and intramuscular carboprost, when administered with oxytocin infusion, prophylactically to decrease blood loss at Cesarean section for labor arrest. Desensitization of the oxytocin receptors has been recently demonstrated in cultured human myometrial cells after continuous and prolonged exposure to oxytocin in-vitro. This could be also the reason for a greater risk of uterine atony and postpartum hemorrhage (PPH) seen in women requiring induction and augmentation of labor. Therefore, addition of a different uterotonic agent, involving a different mechanism of action, to oxytocin infusion is likely to be beneficial, especially in women undergoing CS following failure to progress in labor, who are at a greater risk for PPH.

• Study Type: Interventional
• Enrollment (Actual): 105
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G1X5
      • Mount Sinai Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 51 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• patients who give written informed consent
• patients undergoing Cesarean section for failure to progress in labour, under regional anesthesia
• patients should be in the first stage of labour and have received oxytocin for at least 4 hours

Exclusion Criteria:

• patients who refuse to give written informed consent
• patients who require general anesthesia
• patients who claim allergy or hypersensitivity to oxytocin, ergot derivatives or prostaglandins
• patients with cardiac diseases and hypertension or preeclampsia ( diastolic blood pressure > 90 mmHg, systolic blood pressure > 140 mmHg )
• patients with asthma or any other respiratory disease
• patients with conditions at risk of PPH such as placenta previa, multiple gestation, preeclampsia, macrosomia, polyhydramnios, uterine fibroids, previous history of uterine atony and postpartum bleeding, bleeding diathesis and known infection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Oxytocin only; Oxytocin 5IU IV bolus, followed by an infusion of oxytocin 20IU/L, running at at rate of 40mIU/min for 8 hours	Drug: Oxytocin; Oxytocin 5IU IV bolus, followed by an infusion of oxytocin 20IU/L, running at at rate of 40mIU/min for 8 hours; Other Names: syntocinon
Active Comparator: Oxytocin + Ergot; Oxytocin 5IU IV bolus + Ergot 0.25mg IV, followed by an infusion of oxytocin 20IU/L, running at at rate of 40mIU/min for 8 hours	Drug: Oxytocin; Oxytocin 5IU IV bolus, followed by an infusion of oxytocin 20IU/L, running at at rate of 40mIU/min for 8 hours; Other Names: syntocinon; Drug: Ergot; Ergot 0.25mg IV; Other Names: ergonovine maleate
Active Comparator: Oxytocin + Carboprost; Oxytocin 5IU IV bolus + Carboprost 0.25mg IM, followed by an infusion of oxytocin 20IU/L, running at at rate of 40mIU/min for 8 hours	Drug: Oxytocin; Oxytocin 5IU IV bolus, followed by an infusion of oxytocin 20IU/L, running at at rate of 40mIU/min for 8 hours; Other Names: syntocinon; Drug: Carboprost; Carboprost 0.25mg IM; Other Names: Hemabate®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Need for additional uterotonics intraoperatively	Need for additional uterotonics intraoperatively if requested by the surgeon, YES or NO	1 hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effectiveness of uterine contraction	Adequate/inadequate uterine tone at 3,5 & 10 min	10 min
Need for blood transfusion	Any blood products administered	24 hours
Vital signs	In the OR, heart rate, blood pressure, and oxygen saturation will be measured and looked at for abnormalities	2 hours
Side effects	The presence of nausea, vomiting,other dysrhythmias, chest pain, headache, bronchospasm and any others will be recorded.	24 hours
Estimated blood loss	calculated blood loss = EBV (Pre-op Htc-Post-op Htc) EBV (estimated blood volume, mL)=patient's weight in kg x 85	48 hours
Need for additional uterotonics or interventions post-operatively	Need for additional uterotonics or interventions post-operatively up to 24 hours post-partum	24 hours

Collaborators and Investigators

• Sponsor: Samuel Lunenfeld Research Institute, Mount Sinai Hospital

Publications and helpful links

General Publications

• Balki M, Downey K, Walker A, Seaward G, Carvalho JCA. Prophylactic Administration of Uterotonics to Prevent Postpartum Hemorrhage in Women Undergoing Cesarean Delivery for Arrest of Labor: A Randomized Controlled Trial. Obstet Gynecol. 2021 Mar 1;137(3):505-513. doi: 10.1097/AOG.0000000000004288.

Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2013
• Primary Completion (Actual): July 8, 2019
• Study Completion (Actual): September 30, 2019

Study Registration Dates

• First Submitted: May 31, 2013
• First Submitted That Met QC Criteria: June 4, 2013
• First Posted (Estimate): June 5, 2013

Study Record Updates

• Last Update Posted (Actual): September 24, 2020
• Last Update Submitted That Met QC Criteria: September 22, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: pregnancy; postpartum hemorrhage; Cesarean delivery; failure to progress in labor
• Additional Relevant MeSH Terms: Pathologic Processes; Pregnancy Complications; Obstetric Labor Complications; Puerperal Disorders; Uterine Hemorrhage; Hemorrhage; Dystocia; Postpartum Hemorrhage; Physiological Effects of Drugs; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Oxytocics; Oxytocin; Carboprost; Ergonovine
• Other Study ID Numbers: 13-05