Role Of Different Prophylactic Doses Of Intravenous Tranexamic Acid In Reducing Blood Loss At Caesarean Section

Study Overview
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Brief Summary
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This study aims to define a safe prophylactic intravenous TXA dose with an advantage over others in reducing total blood loss volume at secondary uncomplicated LSCS.

Detailed Description
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Bleeding during vaginal or operative delivery is always of prime concern. Despite significant progress in obstetric care 125,000 women die from obstetric hemorrhage annually in the world. The incidence of CS is increasing, and the average blood loss during CS (1000 mL) is double the amount lost during vaginal delivery (500 mL). CS rate as high as 25-30% in many areas of the world. In Egypt the CS rate is 27.6 %, in United States of America, from 1970-2009 the CS rate rose from 4.5-32.9%, and declined to 32.8% of all deliveries at 2010. In spite of the various measures to prevent blood loss during and after CS, post-partum hemorrhage (PPH) continues to be the most common complication seen in almost 20% of the cases, and causes approximately 25% of maternal deaths worldwide, leading to increased maternal morbidity and mortality. Women who undergo a CS are much more likely to be delivered by a repeat operation in subsequent pregnancies. For women undergoing subsequent CS, the maternal risks are even greater like massive obstetric hemorrhage, hysterectomy, admission to an intensive care unit, or maternal death. Medications, such as oxytocin, misoprostol and prostaglandin F2α, have been used to control bleeding postoperatively. TXA is a synthetic analog of the amino acid lysine,10 as an antifibrinolytic agent it has roughly eight times the antifibrinolytic activity of an older analogue; ε-aminocaproic acid. It competitively inhibits the activation of plasminogen to plasmin, by binding to specific sites of both plasminogen and plasmin, a molecule responsible for the degradation of fibrin, a protein that forms the framework of blood clots. Its intravenous administration has been routinely used for many years to reduce or prevent excessive hemorrhage in various medical conditions or disorders (helping hemostasis), also during and after surgical procedures like benign hysterectomy, open heart surgeries, scoliosis surgery, oral surgery, liver surgeries, total hip or knee arthroplasty, and urology. It has been shown to be very useful and efficient in reducing blood loss and incidence of blood transfusion in these surgeries, and decreases the risk of death in bleeding trauma patients. It was also included in the World Health Organization (WHO) Model List of Essential Medicines. About its role in CS, some recent studies showed that TXA has advantage and useful effect safely in reducing blood loss and requirement of additional ecbolics. Its doses used intravenously to reduce blood loss at CS were a bolus of 1gm, 10 mg/kg, or 15 mg/kg which had an advantage over 10 mg/kg in anemic parturients. No defined safe prophylactic intravenous TXA dose being found in searching literature having an advantage over other doses in reducing total blood loss especially at secondary uncomplicated LSCS.

Official Title
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Comparative Study For Role Of Different Prophylactic Doses Of Intravenous Tranexamic Acid In Reducing Blood Loss At Caesarean Section: A Randomised Controlled Trial

Conditions
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Hemorrhage of Cesarean Section and/or Perineal Wound, Postpartum Hemorrhage

Intervention / Treatment
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* Drug: Normal Saline containing a prophylactic Antibiotic 1 g
* Drug: Tranexamic Acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Maternal average age of 20-40 years. Singleton pregnancy at term between 38±5 days and 40 weeks. Elective planned or emergency secondary lower segment caesarean sections (LSCS). Exclusion Criteria: Women with severe medical and surgical complications as any of the following will be excluded : Heart, liver, kidney, or brain diseases, and blood disorders. Abruptio placenta, and placental abnormalities or accrete syndromes. Polyhydramnios, macrosomia, preeclampsia, or allergy to tranexamic acid. History of thromboembolic disorders, or severe anemia.

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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Will receive a placebo (10 ml of distilled water) in Z solution [500 ml of normal saline containing a prophylactic Antibiotic 1 g] (At 20 minutes preoperatively). | Drug: Normal Saline containing a prophylactic Antibiotic 1 g<br>* 500 ml of normal saline containing a prophylactic Antibiotic 1 g.<br>* Other names: Solution of Sodium Chloride 0.9 %;|
| Active Comparator: T1<br>Will receive Tranexamic acid 15 mg/kg in Z solution [500 ml of normal saline containing a prophylactic Antibiotic 1 g] (At 20 minutes preoperatively). | Drug: Normal Saline containing a prophylactic Antibiotic 1 g<br>* 500 ml of normal saline containing a prophylactic Antibiotic 1 g.<br>* Other names: Solution of Sodium Chloride 0.9 %;Drug: Tranexamic Acid<br>* Tranexamic acid<br>* Other names: TXA;|
| Active Comparator: T2<br>Will receive Tranexamic acid 20 mg/kg in Z solution [500 ml of normal saline containing a prophylactic Antibiotic 1 g] (At 20 minutes preoperatively). | Drug: Normal Saline containing a prophylactic Antibiotic 1 g<br>* 500 ml of normal saline containing a prophylactic Antibiotic 1 g.<br>* Other names: Solution of Sodium Chloride 0.9 %;Drug: Tranexamic Acid<br>* Tranexamic acid<br>* Other names: TXA;|
| Active Comparator: T3<br>Will receive Tranexamic acid 25 mg/kg in Z solution [500 ml of normal saline containing a prophylactic Antibiotic 1 g] (At 20 minutes preoperatively). | Drug: Normal Saline containing a prophylactic Antibiotic 1 g<br>* 500 ml of normal saline containing a prophylactic Antibiotic 1 g.<br>* Other names: Solution of Sodium Chloride 0.9 %;Drug: Tranexamic Acid<br>* Tranexamic acid<br>* Other names: TXA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Blood Loss Volume | Estimating Total Blood Loss Volume (ml) during and after Caesarean Section, up to 6 hours post-operative. | Up to 7 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of surgery | Duration of Caesarean Section estimating (min) | Up to One hour | 
| Hemoglobin level (Hb) | 6 hours post-operative hemoglobin level (mg/dL) estimating. | 6 hours | 
| Maternal weight (W) | 2 hours post-operative maternal weight (kg) estimating | 2 hours | 
| Hematocrit value (Hct) | 6 hours post-operative hematocrit value (%) estimating. | 6 hours | 
| Need for blood or blood products transfusion | Need for other medical measures to arrest and manage bleeding (transfusion of blood or blood products) | Up to 6 hours | 
| Need for additional ecbolics | Need for other medical measures to arrest and manage bleeding if there is a uterine atony (more than five units of intravenous Syntocinon®) | Up to 6 hours | 
| Need for hysterectomy | Need for other surgical measures to arrest and manage bleeding (Hysterectomy) | Up to 6 hours | 
| Need for uterine artery ligation | Need for other surgical measures to arrest and manage bleeding (Uterine artery ligation) | Up to 6 hours | 
| Need for B-lynch | Need for other surgical measures to arrest and manage bleeding if there is a uterine atony (B-lynch) | Up to 6 hours | 
| APGAR Score | APGAR Score as index for any neonatal side effects of medications given | Up to 30 minutes | 
| Any sign for developing a thromboembolic disorder (Maternal) | As index for any maternal side effects of medications given | One week | 
| Blood pressure | Measuring maternal blood pressure (mmHg) immediately postoperative and after 2 hours postoperative. | Up to 2 hours | 
| Pulse rate | Measuring maternal blood puse rate (/minute) immediately postoperative and after 2 hours postoperative. | Up to 2 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Caesarean Section, Tranexamic Acid, Postpartum Hemorrhage, Ecbolics