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

Phase 4

Completed

• Conditions: Hemorrhage of Cesarean Section and/or Perineal Wound; Postpartum Hemorrhage
• Interventions: Drug: Normal Saline containing a prophylactic Antibiotic 1 g; Drug: Tranexamic Acid

• Registration Number: NCT02739815
• Lead Sponsor: Talkha Central Hospital

Brief Summary

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

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.

Study Timeline

• Study Start: 2016-04
• Study First Submitted: 2016-04-04
• Study First Submitted QC: 2016-04-11
• Study First Posted: 2016-04-15
• Status Verified: 2016-06
• Primary Completion: 2016-06
• Study Completion: 2016-06
• Last Update Submitted: 2016-06-14
• Last Update Posted: 2016-06-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 200

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
T1	Normal Saline containing a prophylactic Antibiotic 1 g	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).
T3	Normal Saline containing a prophylactic Antibiotic 1 g	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).
T2	Normal Saline containing a prophylactic Antibiotic 1 g	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).
Placebo	Normal Saline containing a prophylactic Antibiotic 1 g	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).
T1	Tranexamic Acid	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).
T2	Tranexamic Acid	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).
T3	Tranexamic Acid	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).

Primary Outcome Measures

Name	Time	Method
Total Blood Loss Volume	Up to 7 hours	Estimating Total Blood Loss Volume (ml) during and after Caesarean Section, up to 6 hours post-operative.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Al-Azhar University, Faculty of Medicine for Boys ( Cairo ), Al-Hussein University Hospital; 🇪🇬 Cairo, Egypt