Comparing Tranexamic Acid Versus Ecbolics in Preventing Hemorrhage During and After Cesarean Section

The Efficacy and Safety of Tranexamic Acid Versus Uterotonic Agents in Reducing Blood Loss During and After Cesarean Section Among High-risk Patients: a Comparative Study

The study will include 444 pregnant patients undergoing cesarean section in Kasr Al Aini.

Following a proper medical history taking, examination will be done, investigations including laboratory tests and obstetric ultrasound will be done.

Then, the patients will be divided into 4 groups, receiving Oxytocin only (Group 1), Oxytocin + Tranexamic acid (Group 2), Oxtytocin and Misoprostol (Group 3) or Oxytocin and Carbetocin (Group 4) followed by collection of necessary data.

Study Overview

• Status: Not yet recruiting
• Conditions: Cesarean Section Complications; Postpartum Hemorrhage; Blood Loss, Postoperative
• Intervention / Treatment: Drug: Tranexamic acid

Detailed Description

The study will include (444) pregnant women attending for cesarean delivery in Kasr Elaini hospital (faculty of medicine - Cairo university).

The following will be done to all participants:

• Informed written consent: after discussing the nature of the study as well as the expected value, outcome, and possible adverse effects.
• Full medical history: including full obstetric history and current pregnancy history (entailing the 1st day of LMP).
• Thorough Clinical Examination: general (maternal body weight and vital signs) and full obstetric examination.
• Obstetric ultrasonography: to confirm singleton pregnancy, gestational age and the eligibility of the current pregnancy to participate in the study.
• Preoperative laboratory tests: including prothrombin time, prothrombin concentration, complete blood count, and liver and kidney function tests.
• Group allocation: Before surgery, participants will be randomly and equally assigned into four groups; Tranexamic Acid group, Misoprostol group, Carbetocin group and Oxytocin group. Randomization will be performed using computer-generated random numbers.
• In Oxytocin group (n=111), patients will receive 10 IU oxytocin (Syntocinon, Novartis, Basel, Switzerland) given as infusion in 500 ml lactated ringer/s solution at a rate of 125ml/hour after delivery of the placenta.
• In Tranexamic group (n=111), patients will be given 1 gm (10 ml) TXA (Kapron, Amoun, Egypt) diluted in 20 ml of Glucose 5% (administered as intravenous infusion over 5 minutes, at least 15 minutes prior to skin incision).
• In Misoprostol group (n=111), 400 microgram misoprostol (2 tablets - Cytotec, Pfizer, G.D. Searle LLC) will be inserted intraoperative inside the uterus after delivery of the placenta.
• In carbetocin group (n=111) 100 microgram carbetocin (Pabal, Ferring, Kiel, Germany) will be given as an intravenous bolus dose following the delivery of the placenta.
• In all groups, patients will additionally receive 5 IU oxytocin given as slow intravenous bolus following delivery of the baby.
• All cesarean sections will be done under spinal anesthesia by the following operative steps: pfannensteil incision, transverse lower uterine segment incision, immediate cord clamping (< 30 seconds) and the placenta will be removed by controlled cord traction after its spontaneous separation, closure of uterus in 2 layers, closure of anterior abdominal wall in anatomical manner (adequate hemostasis will be ensured in all operative steps).
• The number and the difference of weight of operative towels (before and after LSCS) and amount of blood in suction unit will be recorded.
• Fluid monitoring will be performed through rate of infusion and urine output. A complete blood count test will be performed 12 hours after delivery.
• Estimated Blood Loss (EBL) will be evaluated as follows:
• The number of operative towels used.
• The difference of weight of operative towels (before and after cs) plus the amount of blood in suction unit (we will calculate 1 gram of weight difference equal to 1 ml blood loss).
• EBL calculation according to the formula which is EBL equals EBV times Preoperative hematocrit minus Postoperative hematocrit divided by Postoperative hematocrit.
• Where EBV is estimated blood volume of the patient in mL (equals weight in kg × 85).
• In Tranexamic Acid group (n=111), the time interval between drug administration and fetal delivery will be recorded.
• All patients will be followed up following the delivery as regard occurrence of primary postpartum hemorrhage (within the first 24 hours), the need for blood transfusion (within the first 24 hours), misoprostol-related side effects (in the first 6 hours) (i.e., shivering, pyrexia >38C0, headache, nausea, vomiting with or without the need for antiemetic drugs), carbetocin - related side effects (i.e., nausea, vomiting, flushing, dizziness, syncope) and the occurrence of thromboembolic events (within one week of delivery).
• The EBL will be compared among the four groups together with occurrence of the above-mentioned drugs side effects.

• Study Type: Interventional
• Enrollment (Estimated): 444
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Amr K Rasheed, MsC; Phone Number: 00201228201234; Email: amr_rasheed@hotmail.com
• Study Contact Backup: Name: Moutaz M Elsherbini, MD; Phone Number: 00201001588300; Email: mizosherbini@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 2. Pregnant women candidate for LSCS. 3. Age: 20-40 years old. 4. Full term pregnancies (> 37 weeks confirmed by the 1st day of the LMP or 1st trimesteric ultrasound scan).

  5. Singleton pregnancies. 6. One or more of the following criteria to be considered as high-risk case for PPH (RCOG, 2016):

  1. Maternal Anemia (hemoglobin < 10 g%).
  2. Known placenta previa.
  3. Proven or suspected case of placental abruption.
  4. Preeclampsia or gestational hypertension.
  5. Polyhydramnios (DVP > 8cm).
  6. Macrosomia (> 4 Kg)
  7. Previous history of uterine atony or postpartum hemorrhage).

  8. Prolonged labour (>12 hours).

     7. CS under spinal anesthesia.

     Exclusion Criteria:

• 1. Fetal death (IUFD). 2. Fetal anomalies. 3. IUGR (Estimated fetal weight below the 5th centile) 4. Women presenting with an obstetric emergency necessitating immediate surgery (Cord prolapse, severe antepartum hemorrhage, severe fetal distress etc.) 5. More than 2 previous CS procedures. 6. Prolonged procedure (more than 2 hours from skin incision to skin closure). 7. History of prostaglandin, Tranexamic acid or carbetocin allergy. 8. Multifetal pregnancies. 9. Abnormally invasive placenta. 10. Known deep venous thrombosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Oxytocin Group; o In Oxytocin group (n=111), patients will receive 10 IU oxytocin (Syntocinon, Novartis, Basel, Switzerland) given as infusion in 500 ml lactated ringer/s solution at a rate of 125ml/hour after delivery of the placenta.	Drug: Tranexamic acid; Giving oxytocin only, or oxytocin in addition to Tranexamic acid, Misoprostol or Carbetocin the mentioned doses and by the mention routes, then comparing the estimated blood loss in each group.; Other Names: Oxytocin; Misoprostol; Carbetocin
Active Comparator: Tranexamic acid; o In Tranexamic group (n=111), patients will be given 1 gm (10 ml) TXA (Kapron, Amoun, Egypt) diluted in 20 ml of Glucose 5% (administered as intravenous infusion over 5 minutes, at least 15 minutes prior to skin incision). Oxytocin 5 IU will be given slowly intravenous following delivery of the baby.	Drug: Tranexamic acid; Giving oxytocin only, or oxytocin in addition to Tranexamic acid, Misoprostol or Carbetocin the mentioned doses and by the mention routes, then comparing the estimated blood loss in each group.; Other Names: Oxytocin; Misoprostol; Carbetocin
Active Comparator: Misoprostol; o In Misoprostol group (n=111), 400 microgram misoprostol (2 tablets - Cytotec, Pfizer, G.D. Searle LLC) will be inserted intraoperative inside the uterus after delivery of the placenta Oxytocin 5 IU will be given slowly intravenous following delivery of the baby.	Drug: Tranexamic acid; Giving oxytocin only, or oxytocin in addition to Tranexamic acid, Misoprostol or Carbetocin the mentioned doses and by the mention routes, then comparing the estimated blood loss in each group.; Other Names: Oxytocin; Misoprostol; Carbetocin
Active Comparator: Carbetocin; o In carbetocin group (n=111) 100 microgram carbetocin (Pabal, Ferring, Kiel, Germany) will be given as an intravenous bolus dose following the delivery of the placenta. Oxytocin 5 IU will be given slowly intravenous following delivery of the baby.	Drug: Tranexamic acid; Giving oxytocin only, or oxytocin in addition to Tranexamic acid, Misoprostol or Carbetocin the mentioned doses and by the mention routes, then comparing the estimated blood loss in each group.; Other Names: Oxytocin; Misoprostol; Carbetocin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Estimated Blood Loss	To compare the estimated blood loss (EBL) during and after cesarean delivery among the four groups.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Need for additional ecbolics	The Use of additional ecbolics denoting uterine atony (i.e. 10 IU intravenous infusion of oxytocin with 500 ml lactated ringer at a rate of 125 ml/hour and 1mL [0.2 mg] intramuscular ergometrine with or without 600 microgram rectal misoprostol postoperatively)	1 year
Excessive blood loss and need for blood transfusion	The occurrence of excessive blood loss (> 1000 mL) together with the need for blood transfusion within the first 24 hours postoperatively.	1 year
Side effects	The occurrence of any maternal side effects (among the four groups).	1 year

Collaborators and Investigators

• Sponsor: Cairo University
• Investigators: Principal Investigator: Amr K Rasheed, MsC, Assistant Lecturer, Cairo University

Publications and helpful links

General Publications

• Chen CY, Su YN, Lin TH, Chang Y, Horng HC, Wang PH, Yeh CC, Chang WH, Huang HY. Carbetocin in prevention of postpartum hemorrhage: Experience in a tertiary medical center of Taiwan. Taiwan J Obstet Gynecol. 2016 Dec;55(6):804-809. doi: 10.1016/j.tjog.2016.07.009.
• Prata N, Weidert K. Efficacy of misoprostol for the treatment of postpartum hemorrhage: current knowledge and implications for health care planning. Int J Womens Health. 2016 Jul 29;8:341-9. doi: 10.2147/IJWH.S89315. eCollection 2016.
• Della Corte L, Saccone G, Locci M, Carbone L, Raffone A, Giampaolino P, Ciardulli A, Berghella V, Zullo F. Tranexamic acid for treatment of primary postpartum hemorrhage after vaginal delivery: a systematic review and meta-analysis of randomized controlled trials. J Matern Fetal Neonatal Med. 2020 Mar;33(5):869-874. doi: 10.1080/14767058.2018.1500544. Epub 2018 Sep 10.

Study record dates

Study Major Dates

• Study Start (Estimated): October 15, 2023
• Primary Completion (Estimated): August 31, 2024
• Study Completion (Estimated): August 31, 2024

Study Registration Dates

• First Submitted: September 23, 2023
• First Submitted That Met QC Criteria: September 28, 2023
• First Posted (Actual): September 29, 2023

Study Record Updates

• Last Update Posted (Actual): September 29, 2023
• Last Update Submitted That Met QC Criteria: September 28, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pregnancy Complications; Obstetric Labor Complications; Puerperal Disorders; Uterine Hemorrhage; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Hemorrhage; Postpartum Hemorrhage; Postoperative Hemorrhage; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Gastrointestinal Agents; Antifibrinolytic Agents; Hemostatics; Coagulants; Reproductive Control Agents; Anti-Ulcer Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Oxytocics; Oxytocin; Tranexamic Acid; Misoprostol; Carbetocin
• Other Study ID Numbers: MD-147-2021

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