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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Postpartum Hemorrhage

Intervention / Treatment
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* Drug: carbetocin
* Drug: Tranexamic acid plus misoprostol
* Drug: misoprostol


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: carbetocin<br>Carbetocin 100 microgram will be applied intravenously in a short infusion over about a minute | Drug: carbetocin<br>* Carbetocin 100 microgram will be applied intravenously in a short infusion over about a minute<br>* Other names: Active Comparator;|
| Experimental: Tranexamic acid plus misoprostol<br>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<br>* 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.<br>* Other names: active comparator;|
| Active Comparator: misoprostol<br>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<br>* 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.<br>* Other names: active comparator;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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carbetocin, tranexamic acid, postpartum hemorrhage, buccal misoprostol