Carbetocin Versus Oral Tranexamic Acid Plus, Buccal Misoprostol on Blood Loss After Vaginal Delivery

The Effect of Carbetocin Versus Oral Tranexamic Acid Plus, Buccal Misoprostol on Blood Loss After Vaginal Delivery: a Randomized Controlled Trial

Excessive bleeding at or after childbirth accounts for about half of all the post-partum maternal deaths in developing countries and is the single most important cause of maternal mortality worldwide. Post-partum hemorrhage (PPH) is the major contributor to maternal mortality worldwide representing at least 25% of the maternal deaths annually. Prevention of PPH has become a global aim to reduce maternal mortality. Uterine atony is the main cause of PPH; therefore, active management of the third stage of labor has emerged as a most actual tool in its prevention. The previous study in Egypt recorded that 88% of deaths from PPH occur within 4 hours of delivery. Tranexamic acid (TA) is an antifibrinolytic agent that blocks the lysine-binding site of plasminogen to fibrin. Misoprostol is effective when given orally, buccal, sublingually, vaginally, or rectally, so it might be used by traditional birth attendants, or self-administered, in cases of home-births occurred without the attendance of health personnel or where women are at most risk for occurrence of severe PPH. So, the current study aims to evaluate the effect of prophylactic oral TA plus buccal misoprostol in the prevention of primary PPH after routine active management of the third stage of labor in women at low risk for uterine atony in comparison with carbetocin and buccal misoprostol alone.

Study Overview

• Status: Completed
• Conditions: Postpartum Hemorrhage
• Intervention / Treatment: Drug: carbetocin; Drug: Tranexamic acid plus misoprostol; Drug: misoprostol

Detailed Description

All women admitted to the reception unit for vaginal delivery were invited to participate in the study. The investigators included women aged (20-35 years) with a singleton pregnancy in a cephalic presentation between 38 and 42 weeks gestation. The participated women have entered the screening phase of the study. This phase included history taking (age, parity, and gestational age) with measurement of weight, temperature, and initial hemoglobin level. The investigators excluded women with medical disorders such as cardiac, hepatic, renal, neurologic disorders thromboembolic disease, blood disorders, diabetes, gestational hypertension, and pre-eclampsia. Women at risk for PPH as grand multipara (parity >5), multiple pregnancies, polyhydramnios, fetal macrosomia, antepartum hemorrhage, prolonged, and obstructed labor were also excluded. Moreover, we excluded women with a scarred uterus or previous instrumental delivery and those suffering from hypersensitivity to TA. women were allocated to one of the three study groups: group I (carbetocin group) received 100 mc carbetocin IV after delivery of the baby, group II (misoprostol group) received 600 mg buccal misoprostol after delivery of the baby, and group III (TA plus misoprostol group) received 1000mg oral TA at the end of the first stage of labor plus 600 mg buccal misoprostol after delivery of the baby. A buccal route, in which the tablets are placed in the cheek for 30 min after which any remnants are swallowed.

• Study Type: Interventional
• Enrollment (Actual): 360
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Aswan, Egypt, 81528
    • Aswan University
  • Aswan, Egypt, 81528
    • AswanUH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 40 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• All women admitted to the reception unit for vaginal delivery
• women aged (20-35 years) with a singleton pregnancy in a cephalic presentation between 38 and 42 weeks gestation.

Exclusion Criteria:

• medical disorders such as cardiac, hepatic, renal, neurologic disorders thromboembolic disease, blood disorders, diabetes, gestational hypertension, and pre-eclampsia.

-Women at risk for PPH as grand multipara (parity >5), multiple pregnancies, polyhydramnios, fetal macrosomia, antepartum hemorrhage, prolonged, and obstructed labor were also excluded.-

• Moreover, we excluded women with a scarred uterus or previous instrumental delivery and those suffering from hypersensitivity to TA.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: carbetocin; Carbetocin 100 microgram will be applied intravenously in a short infusion over about a minute	Drug: carbetocin; Carbetocin 100 microgram will be applied intravenously in a short infusion over about a minute; Other Names: Active Comparator
EXPERIMENTAL: Tranexamic acid plus misoprostol; 1000mg oral TA at the end of the first stage of labor plus 600 mg buccal misoprostol after delivery of the baby. A buccal route, in which the tablets are placed in the cheek for 30 min after which any remnants are swallowed.	Drug: Tranexamic acid plus misoprostol; 1000mg oral TA at the end of the first stage of labor plus 600 mg buccal misoprostol after delivery of the baby. A buccal route, in which the tablets are placed in the cheek for 30 min after which any remnants are swallowed.; Other Names: active comparator
ACTIVE_COMPARATOR: misoprostol; 600 mg buccal misoprostol after delivery of the baby. A buccal route, in which the tablets are placed in the cheek for 30 min after which any remnants are swallowed.	Drug: misoprostol; 600 mg buccal misoprostol after delivery of the baby. A buccal route, in which the tablets are placed in the cheek for 30 min after which any remnants are swallowed.; Other Names: active comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
difference in the mean blood loss at 4 h postpartum between the three groups	measure blood loss by direct and gravimetric methods	4 hours post delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
difference in hemoglobin level	hemoglobin level pre delivery and 24 hours post delivery	24 hours postdelivery
the need for additional uterotonics	the need of additional oxytocin or misoprostol	ist 24 hours postoperative

Collaborators and Investigators

• Sponsor: Aswan University Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 1, 2018
• Primary Completion (ACTUAL): May 31, 2020
• Study Completion (ACTUAL): July 1, 2020

Study Registration Dates

• First Submitted: October 13, 2018
• First Submitted That Met QC Criteria: October 13, 2018
• First Posted (ACTUAL): October 17, 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: 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/293/9/18

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