Tranexamic Acid for the Control of Blood Loss at Elective Cesarean Section

A Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing a Standard 1gm and a Low Dose 0.5gm IV Tranexamic Acid for the Control of Blood Loss at Elective Cesarean Section

The aim of the study is to determine, out of two doses (a standard and a low dose) compared to placebo, the optimal and minimal dose of an intravenously administered single bolus of tranexamic acid(TA) to reduce blood loss when administered during cesarean section(CS). Tranexamic acid is an antifibrinolytic agent, which causes a reversible and competitive blockade of the lysine binding sites on plasminogen molecules. It is a synthetic analog of the amino acid lysine and its action is to reduce blood loss. TA is widely in use in the field of obstetrics. Both antepartum and postpartum hemorrhage(PPH) is being treated by TA extensively. One study demonstrated for the first time that TA administered to women with overt PPH decreases blood loss and maternal morbidity. Prevention of PPH is another indication where TA has been used. Varied doses of TA ranging from 1 mg/kg to more than 100 mg/kg have been used in various surgeries. Even in studies involving CS, the doses used were either a bolus of 1 gm or 10 mg/kg intravenously.

The dose of 1 g or 10 mg/kg is commonly used prophylactically before CS, Because of the lack of data on lower doses and TA pharmacokinetics, a low 0.5-g dose should be tested.

Study Overview

• Status: Completed
• Conditions: Cesarean Section Complications
• Intervention / Treatment: Drug: normal saline; Drug: 1gm tranexamic acid; Drug: 0.5 gm tranexamic acid

Detailed Description

CS was carried out under subarachnoid block using 2-2.5 ml of 0.5% hyperbaric bupivacaine after an informed written consent. Blockade up to T4-T6 level was considered an adequate level of anesthesia. After delivery of the neonate, 20 unit of oxytocin in 500 ml normal saline will begive at the rate of 8 mU/min intravenously.

All consenting patients were recruited as a consecutive series to one of the three study groups of 120 patients each, based on block random allocation protocol. Neither the patient nor the investigator was aware of the group assignment. An anesthesiologist not related to the study prepared the drug for every patient.

Groups were labeled as follows:

Group one (120) - 5 ml of distilled water in 20 ml of 5% dextrose

Group two (120) - TA in the dose of I gm in 20 ml of 5% dextrose

Group three(120) - TA in the dose of 0.5gm in 20 ml of 5% dextrose.

The drug in all the groups was given intravenously over 20 min before skin incision.

Monitoring of the pulse rate, blood pressure, Pulse Oximetry (SpO2) and Electrocardiograph (ECG) was carried out every 2 min up to 10 min of starting the study drug; then every 5 min until the delivery of the baby and thereafter every 15 min until the end of the surgery. Blood loss was measured intra-operatively and postoperatively up to 24 h. All material such as sponges, mops, pads, and drapes were weighed with an electronic weighing scale before and at the end of surgery. A volume of blood in the suction bottle was considered only after the placental delivery, to exclude any amniotic fluid volume. The quantity of intra-operative blood loss (ml) = (weight of the abdominal swabs and drapes after CS - weight of materials prior to CS) + (the volume in the suction bottle after placental delivery in ml). Post-operative blood loss was measured by weighing and numbering the vaginal pads used by the patient after completion of CS 2 hourly up to 6 h and then 6 hourly up to 24 h.

Uterine contractility, placental separation, neonatal condition and any side effect caused by TA will be noted. Intramuscular methylergometrine would be used as a rescue uterotonic treatment when required. Post-operative hemoglobin, hematocrit, serum creatinine, and prothrombin time, values were recorded at 24 h. All the parturients were encouraged to start early leg exercises and ambulation in the post-operative period.

• Study Type: Interventional
• Enrollment (Actual): 360
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • Aswan, Egypt, 81528
    • Aswan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 45 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria: all pregnant women scheduled for elective cesarean -

Exclusion Criteria:

• Patients with a cardiac, hepatic, renal or thromboembolic disease.

• patients had an allergy to tranexamic acid

  . -patients who had received platelet antiaggregant such as Aspirin in the week before surgery

• patient refusing to be a participant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: normal saline; the patients receives 110 ml normal saline IV just before skin incision	Drug: normal saline; 110 ml normal saline IV just before skin incision; Other Names: placebo comparator
ACTIVE_COMPARATOR: 1gm tranexamic acid; 1 gm tranexamic acid (2 ampoules of Capron 500 mg /5 ml; Cairo, Egypt) intravenous just before skin incision	Drug: 1gm tranexamic acid; 1 gm tranexamic acid (2 ampoules of Capron 500 mg /5 ml; Cairo, Egypt) intravenous just before skin incision; Other Names: active comparator
ACTIVE_COMPARATOR: 0.5 gm tranexamic acid; 0.5 gm tranexamic acid (1 ampoule of Capron 500 mg /5 ml; Cairo, Egypt) intravenous just before skin incision	Drug: 0.5 gm tranexamic acid; 0.5 gm tranexamic acid (2 ampoules of Capron 500 mg /5 ml; Cairo, Egypt) intravenous just before skin incision; Other Names: active comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
intraoperative blood loss	amount of blood loss during the operation	during the operation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
postoperative blood loss	amount of blood loss 6 hours post operative	6 hours post operative
Number of participants need of uterotonic	Number of participants need of extra uterotonic	24 hours post operative
Number of participants need blood transfusion	Number of participants need of blood transfusion	24 hours post operative

Collaborators and Investigators

• Sponsor: Aswan University Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2018
• Primary Completion (ACTUAL): March 30, 2020
• Study Completion (ACTUAL): August 1, 2020

Study Registration Dates

• First Submitted: October 13, 2018
• First Submitted That Met QC Criteria: October 17, 2018
• First Posted (ACTUAL): October 18, 2018

Study Record Updates

• Last Update Posted (ACTUAL): August 5, 2020
• Last Update Submitted That Met QC Criteria: August 3, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: cesarean section; tranexamic acid; postpartum hemorrhage
• 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: aswu/276/7/18

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No