Carbetocin Versus Buccal Misoprostol Plus IV Tranexamic Acid for Prevention of Postpartum Hemorrhage at Cesarean Section

Carbetocin Versus Buccal Misoprostol Plus IV Tranexamic Acid for Prevention of Postpartum Hemorrhage at Cesarean Section: A Double-blind, Randomized, Placebo-controlled Trial

The Millennium Development Goal of reducing the maternal mortality ratio by 75 % by 2015 will remain beyond our reach unless we prioritize the prevention and treatment of postpartum hemorrhage(PPH) in low-resource countries. Consequently, the administration of uterotonic drugs during cesarean section (CS) and in the third stage of labor for vaginal delivery has become essential to diminish the risk of PPH and improve maternal safety.

Oxytocin is regarded as the gold standard uterotonic agent but only has a half-life of 4-10 min; therefore, at cesarean section oxytocin must be administered as a continuous intravenous infusion to attain sustained uterotonic activity throughout the surgical procedure and immediate postpartum period.

Misoprostol is a prostaglandin E1 analog proven in several randomized controlled trials to be effective in preventing PPH because of its strong uterotonic effects. In addition, misoprostol is inexpensive, stable at room temperature, and easy to administer.

Misoprostol has been broadly studied in the prevention and treatment of PPH after vaginal delivery; however, its use in conjunction with CS has not been investigated as much.

The buccal route is recognized as having the greatest benefit due to its rapid uptake, long-acting effect, and greatest bioavailability compared with other routes of misoprostol administration.

Carbetocin is a long-acting synthetic analog of oxytocin that can be administered as a single-dose injection; intravenously administered carbetocin has a half-life of approximately 40 min.

A single intravenous bolus of carbetocin produces a tetanic uterine contraction within 2 min and persists for an average of 60 min following injection.

The aim of this study was to compare the effectiveness of combined buccal misoprostol and IV tranexamic acid (TA)with intravenous carbetocin for prevention of PPH in patients with risk factors during cesarean section.

Study Overview

• Status: Completed
• Conditions: Cesarean Section Complications
• Intervention / Treatment: Drug: carbetocin; Drug: Tranexamic Acid; Drug: misoprostol

Detailed Description

Eligible and consenting participants were randomized via a computer-generated random number sequence into one of two groups: one group received a pre-prepared sealed and opaque packet containing 400 μg of misoprostol (2 tablets of 200 μg), 2 ampoules of TA. The other group received similar packets containing two placebo tablets, two placebo ampoules (distilled water) and separate carbetocin ampoule (100 μg) for slow intravenous injection. The misoprostol and placebo tablets were similar in size, shape, and color, and ampoules of TA and carbetocin will be also similar to placebo. Randomization was done by the resident doctors immediately before transfer to the theater, whereas preparation of packets and confidential record maintenance was done by the labor room nursing staff.

Study drug administration Group 1 100 μg carbetocin ampoule will be diluted in 10 mL normal saline and administered slowly (over 30-60 s) intravenously by the anesthetist after the birth of the baby

Group 2 400 μg buccal misoprostol (2 tablets of 200 μg) will be given after spinal anesthesia and few minutes before skin incision in addition to 1 gm tranexamic acid in 100 mL of intravenous solution infusion over 15 min.

.

• Study Type: Interventional
• Enrollment (Actual): 400
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Aswan, Egypt, 81528
    • Aswan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• pregnant women scheduled for an elective cesarean section with at least one risk factor for postpartum hemorrhage

Exclusion Criteria:

• suspected coagulopathy
• women refuse to participate
• emergent cesarean section
• allergy to misoprostol or tranexamic acid or carbetocin
• known deep venous thrombosis
• general anesthesia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: carbetocin; 100 μg carbetocin ampoule will be diluted in 10 mL normal saline and administered slowly (over 30-60 s) intravenously by the anesthetist after the birth of the baby	Drug: carbetocin; 100 μg carbetocin ampoule will be diluted in 10 mL normal saline and administered slowly (over 30-60 s) intravenously by the anesthetist after the birth of the baby; Other Names: Active Comparator
Experimental: Tranexamic acid plus misoprostol; 400 μg buccal misoprostol (2 tablets of 200 μg) will be given after spinal anesthesia and few minutes before skin incision in addition to 1 gm tranexamic acid in 100 mL of intravenous solution infusion over 15 min.	Drug: Tranexamic Acid; 1 gm tranexamic acid in 100 mL of intravenous solution infusion over 15 min.; Other Names: Experimental; Drug: misoprostol; Group 2 400 μg buccal misoprostol (2 tablets of 200 μg) will be given after spinal anesthesia and few minutes before skin incision; Other Names: expremental

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants require additional pharmacological uterotonic.	Number of participants need extra uterotonic	ist 24 hours post operative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
intraoperative blood loss	amount of blood loss during cesarean section	during the operation
post operative blood loss	amount of blood loss after cesarean section	24 hours post operative
Number of participants need for blood transfusion	Number of participants needed for transfusion	24 hours post operative

Collaborators and Investigators

• Sponsor: Aswan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2018
• Primary Completion (Actual): May 30, 2020
• Study Completion (Actual): August 1, 2020

Study Registration Dates

• First Submitted: October 13, 2018
• First Submitted That Met QC Criteria: October 15, 2018
• First Posted (Actual): October 18, 2018

Study Record Updates

• Last Update Posted (Actual): August 5, 2020
• Last Update Submitted That Met QC Criteria: August 3, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: cesarean section; tranexamic acid; postpartum hemorrhage; buccal misoprostol; carbetocin
• Additional Relevant MeSH Terms: Pathologic Processes; Pregnancy Complications; Obstetric Labor Complications; Puerperal Disorders; Uterine Hemorrhage; Hemorrhage; Postpartum Hemorrhage; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Gastrointestinal Agents; Antifibrinolytic Agents; Hemostatics; Coagulants; Reproductive Control Agents; Anti-Ulcer Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Oxytocics; Tranexamic Acid; Misoprostol; Carbetocin
• Other Study ID Numbers: aswu/274/7/18

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No