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

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).

Study Overview

• Status: Completed
• Conditions: Obstetrical Hemorrhage
• Intervention / Treatment: Drug: transamin

• Study Type: Interventional
• Enrollment (Actual): 450
• Phase: Phase 3

Contacts and Locations

Study Locations

• Turkey
  • Bakırkoy
    • İstanbul, Bakırkoy, Turkey, 34142
      • Bakıryok Women and Children Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

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: tranexamic acid; TA administered intravenously over a 5 min period at delivery of the anterior shoulder	Drug: transamin; TA was administered intravenously over a 5 min period at delivery of the anterior shoulder
No Intervention: saline; 10 mL of saline was administered intravenously over a 5 min period at delivery of the anterior shoulder

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Erzincan Military Hospital

Publications and helpful links

General Publications

• Gungorduk K, Asicioglu O, Yildirim G, Ark C, Tekirdag AI, Besimoglu B. Can intravenous injection of tranexamic acid be used in routine practice with active management of the third stage of labor in vaginal delivery? A randomized controlled study. Am J Perinatol. 2013 May;30(5):407-13. doi: 10.1055/s-0032-1326986. Epub 2012 Sep 21.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: April 11, 2011
• First Submitted That Met QC Criteria: April 18, 2011
• First Posted (Estimate): April 19, 2011

Study Record Updates

• Last Update Posted (Estimate): November 17, 2011
• Last Update Submitted That Met QC Criteria: November 16, 2011
• Last Verified: November 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Antifibrinolytic Agents; Hemostatics; Coagulants; Tranexamic Acid
• Other Study ID Numbers: gungorduk12