Clinical Study to Assess the Equivalence of Tranexamic Acid vs Oxytocin in Reducing the PPH (TRANOXY2015)

Study Overview
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Brief Summary
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The purpose of this study was to evaluate that the tranexamic acid (TXA)Intravenous and oral, is equivalent oxytocin (OXY),intramuscularly, in reducing the blood loss in post partum period (mL) in patients at the end of pregnancy ( 37-42 w ) at low risk of post partum hemorrhage (PPH). The PPH means a blood loss equal to or greater than 500 ml after a vaginal delivery ( the bleeding is defined severe if it exceeds 1000 mL). PPH is called primary when blood loss arose within 24 hours after birth. This is a open-trial randomized, longitudinal, controlled that including 486 subjects .

Detailed Description
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This trial includes three arms of treatment : arm A (IMP1Test): TXA 500mg/ 2 vials (1 gr) oral within 5 minutes from the delivery (third stage af labor) arm B (IMP2Test): TXA 500 mg/ 2 vials (1 gr) slow intravenous infusion 1ml/min within 5 minutes from the delivery(third stage af labor) arm C (control): OXY 5 IU/ml/ 2 vials (10 International Unit) intramuscularly within 5 minutes from the delivery (third stage af labor) The clamping of the umbilical cord will be executed immediately after birth The randomization 1:1:1 (block design), generated by the computer. Primary outcomes: assessment of total blood loss expressed in mL immediately after delivery two hours after delivery The measurement of the overall blood loss at delivery (ml) will be performed by the graduated bag, immediately after birth. The measurement two hours after delivery will be performed by weighing of the adsorbent material [ N.ml = N. gr indicated by the balance - dry weight of the sanitary napkin]. The overall loss in blood measured (ml) two hours of delivery will then be performed by adding the two collections.

Official Title
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Clinical Study,Longitudinal,Controlled, Randomized, Open-label, Phase III,to Assess the Equivalence of Tranexamic Acid vs Oxytocin in Reducing the Post Partum Hemorrhage (PHH) in Patients at the End of Pregnancy (37-42 w) at Low Risk of PPH

Conditions
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Postpartum Hemorrhage

Intervention / Treatment
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* Drug: Tranexamic Acid
* Drug: Tranexamic Acid
* Drug: Oxytocin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects at the end of pregnancy ( 37-42 w ) at low risk of PPH Mean by low-risk of PPH subjects without any of the following risk factors : hypertension/preeclampsia, placental abruption during pregnancy , placenta previa , tocolysis two hours before delivery, multiple pregnancy , previous PPH, obesity ( BMI > 35 ), anemia (Hb < 7 g/dL), elective caesarean section , induction of labor, retention of placental material , polyhydramnios , fever during labor, use of high doses of heparin low molecular weight. Subjects full capacity and the willingness to give written informed consent . Exclusion Criteria: Subjects with preterm pregnancy (<37 weeks ) or with prolonged pregnancy ( > 42 weeks ) Subjects at the end of pregnancy ( 37 weeks - 42 weeks ) with the following risk factors for PPH (Tab1) multiple pregnancy history of thromboembolic disease or high incidence of thromboembolic events in family history ( patients at high risk of thrombophilia ) Patients with Long - QT syndrome or who are taking drugs that cause QT prolongation Intrauterine fetal Death epilepsy autoimmune disease Tab1 medical history : Placental abruption during pregnancy placenta previa Hypertension / preeclampsia previous PPH polyhydramnios Obesity ( BMI > 35 ) Anemia ( < 7 g / dL ) Detectable in labor: Elective caesarean section Tocolysis two hours before delivery Induction of labor Retention of placental material Fever during labor Use of low molecular weight heparin

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: arm A<br>2 vials ( =1 gram) of Tranexamic Acid oral administered within 5 minutes from the delivery (third stage after labor) | Drug: Tranexamic Acid<br>* 2 vials ( =1 gram) of Tranexamic Acid oral administered within 5 minutes from the delivery (third stage after labor) 2 vials (=1 gram ) of Tranexamic Acid administered slow intravenous infusion within 5 minutes from the delivery (third stage after labor)<br>* Other names: TXA;|
| Experimental: arm B<br>2 vials (=1 gram ) of Tranexamic Acid administered slow intravenous infusion within 5 minutes from the delivery(third stage after labor) | Drug: Tranexamic Acid<br>* 2 vials ( =1 gram) of Tranexamic Acid slow intravenous infusion administered within 5 minutes from the delivery (third stage after labor)<br>* Other names: TXA;|
| Active Comparator: arm C<br>2 vials (=10 IU/International Unit) of oxytocin administered intramuscularly within 5 minutes from the delivery (third stage after labor) | Drug: Oxytocin<br>* 2 vials (=10 IU/International Unit) of oxytocin administered intramuscularly within 5 minutes from the delivery (third stage after labor)<br>* Other names: OXY;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| assessment of total blood loss expressed in mL | global blood loss > 500 mL | immediately after delivery | 
| assessment of total blood loss expressed in mL | global blood loss > 500 mL | two hours after delivery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| assessment of the number of hemodynamic changes | hypotension (number of women with Arterial Pressure < 100/60 mm/Hg ) | immediately after delivery | 
| assessment of the number of hemodynamic changes | hypotension (number of women with Arterial Pressure < 100/60 mm/Hg ) | two hours after delivery | 
| assessment of the number of hemodynamic changes | increased heart rate (number of women with Heart Rate > 60 bpm ) | immediately after delivery | 
| assessment of the number of hemodynamic changes | increased heart rate (number of women with Heart Rate > 60 bpm ) | two hours after delivery | 
| assessment of the need of using additional uterotonic | administration additional drug for the treatment of PPH | immediately after delivery | 
| assessment of the need of using additional uterotonic | administration additional drug for the treatment of PPH | two hours after delivery | 
| assessment the need for surgical manoeuvres for the bleeding control | need of intrauterine balloon or uterine compression sutures for surgical treatment of the PPH or hysterectomy | immediately after delivery | 
| assessment the need for surgical manoeuvres for the bleeding control | need of intrauterine balloon or uterine compression sutures for surgical treatment of the PPH or hysterectomy | two hours after delivery | 
| assessment the need for the blood transfusions | Hb <7 g/dL | two days after delivery |