Can we Use Intravenous Injection of Tranexamic Acid in Routine Practice With Active Management of the Third Stage of Labor?

Study Overview
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Brief Summary
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Obstetrical hemorrhage accounts for nearly one quarter of all maternal deaths worldwide and was the most common cause of maternal death in the Turkey [1,2]. Most of these deaths occur within 4 h of delivery and are a result of problems during third and fourth stages of labor. It also contributes significantly to serious maternal morbidity. Obstetric, surgical and radiological interventions play central role in the management of obstetric hemorrhage; however, pharmacologic management and in particular prohemostatic therapies also play an important role in the final maternal outcome. Administration of tranexamic acid (TA), intravenously in the third stage of labor may be one of these methods. TA a synthetic derivate of the amino acid lysine, is an antifibrinolytic that reversibly inhibits the activation of plasminogen, thus inhibiting fibrinolysis and reducing bleeding. TA may enhance the effectiveness of the patient's own hemostatic mechanism [3,4]. In nonobstetric surgery, a systematic review of randomized controlled trails showed that tranexamic acid reduced the risk of blood transfusion [ relative risk (RR) 0.61; 95% CI 0.54-0.69] and also reduced the need for re-operation as a result of bleeding (RR 0.67; 95% CI 0.41-1.09). There was no evidence for an increased risk of thrombotic events [5]. In gynecology and obstetrics, TA is most commonly used to treat idiopathic menorrhagia, and is an effective and well-tolerated treatment when administered orally [5,6,7]. Bleeding associated with pregnancy (placental abruption, placenta previa) has also been treated with TA [6]. Furthermore, four randomized controlled studies have shown that TA reduces postpartum hemorrhage (PPH) following cesarean delivery [7-11]. Only one randomized trail is available evaluating the effect of TA use to prevent bleeding in the postpartum period following spontaneous vaginal delivery [12]. The purpose of our study was to estimate the effect of the addition of intravenous TA to a standard active management of the third stage of labor (which includes prophylactic injection of 10 IU of oxytocin within two minutes of birth, early clamping of the umbilical cord, and controlled cord traction).

Conditions
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Obstetrical Hemorrhage

Intervention / Treatment
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* Drug: transamin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: gestational age between 37 and 42 weeks, live fetus, cephalic presentation, vaginal birth. Patients who had a risk factors for PPH, such as multiple gestation, polyhydramnios, fetal macrosomia, antepartum hemorrhage, anemia (haemoglobin concentration < 8 g/dL), severe pre-eclampsia, or coagulopathy Exclusion Criteria: placenta previa, placental abruption, cesarean section or any uterine scar, abnormal placentation (accreta, increta, or percreta), a current or previous history of significant disease, including heart disease, liver, renal disorders.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: tranexamic acid<br>TA administered intravenously over a 5 min period at delivery of the anterior shoulder | Drug: transamin<br>* TA was administered intravenously over a 5 min period at delivery of the anterior shoulder<br>|
| No Intervention: saline<br>10 mL of saline was administered intravenously over a 5 min period at delivery of the anterior shoulder | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The amount of blood loss in the third and fourth stages (the fourth stage of labor begins with delivery of the placenta and ends 2 hours after delivery) of labor. | The volume of blood loss was measured by weighing a sheet soaked from the end of the delivery to 2h after birth. We used a specially designed operating sheet and an electronic scale to weigh all the material (with a 1 g deviation range). The quantity of blood (ml) = (weight of used materials - weight of materials prior to use)/1.05. | 2 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| incidences of PPH >500 ml | The quantity of blood (ml) = (weight of used materials - weight of materials prior to use)/1.05 > 500 mL | 2 hours | 
| the incidences of severe postpartum hemorrhage | The quantity of blood (ml) = (weight of used materials - weight of materials prior to use)/1.05 ≥1000 ml | 2 hours | 
| need for additional uterotonic drugs | need for additional uterotonic drugs such as 200 µg intravenous metylergometrine, 20 IU oxytocin infusion in 500 ml ringer lactate, and/or 800 misoprostol rectally for vaginal bleeding | 2 hours | 
| side effects at time of TA injection | nausea, vomiting or diarrhea | 2 hours |