Tranexamic Acid Versus Sublingual Misoprostol in Reducing Blood Loss During Elective CS in High Risk Cases

The Efficacy and Safety of Preoperative Intravenous Tranexamic Acid Versus Sublingual Misoprostol in Reducing Blood Loss During and After Elective Cesarean Section Among High Risk Pregnant Cases.

The Efficacy and safety of Preoperative Intravenous Tranexamic acid versus Sublingual misoprostol in reducing blood loss during and after Elective Cesarean section among high risk pregnant cases.

Study Overview

• Status: Unknown
• Conditions: Post Partum Hemorrhage
• Intervention / Treatment: Drug: Tranexamic acid; Drug: Misoprostol; Drug: Oxytocin

Detailed Description

The study will include (345) pregnant women attending for elective cesarean delivery in the Kasr Elaini hospital (faculty of medicine - Cairo university).

All the patients will be subjected to informed written consent, full medical history, clinical examination, obstetric ultrasonography, preoperative laboratory tests On the day of the scheduled surgery, participants will be randomly and equally assigned into three groups. Tranexamic group, Misoprostol group and oxytocin-only group (control group). Randomization will be performed using computer-generated random numbers.

In Tranexamic group (n=115), patients will be given 1 gm (10 ml) Tranexamic acid (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=115), 400 microgram misoprostol (2 tablets - Cytotec, Pfizer, G.D. Searle LLC) will be administered sublingually by the patients immediately before starting skin incision.

Following the delivery of the baby, patients in both Tranexamic and Misoprostol groups will additionally receive an intravenous bolus of 5 IU oxytocin (Syntocinon, Novartis, Basel, Switzerland) and 20 IU oxytocin in 500 mL lactated Ringer's solution (infused at a rate of 125 mL/h).

In oxytocin-only group (n=115), patients will receive an intravenous bolus of 5 IU oxytocin (Syntocinon, Novartis, Basel, Switzerland) and 20 IU oxytocin in 500 mL lactated Ringer's solution (infused at a rate of 125 mL/h) following the delivery of the baby.

All cesarean sections will be done under spinal anesthesia by the following operative steps: pfannenstiel 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 CS) 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).
• the following formula: EBL= EBV x [(Preoperative hematocrit- Postoperative hematocrit)/ Postoperative hematocrit] Where EBV is estimated blood volume of the patient in mL (equals weight in kg × 85).

The time interval between drug administration and fetal delivery will be recorded together with the neonatal outcome (APGAR at 1 and 5 minutes, NICU admission and neonatal death).

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 >38 C, headache, nausea, vomiting with or without the need for antiemetic drugs) and the occurrence of thromboembolic events (within one week of delivery).

• Study Type: Interventional
• Enrollment (Anticipated): 345
• Phase: Phase 2

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt
    • Recruiting
    • Faculty of Medicine
    • Contact: Moutaz Sherbini, MD; Phone Number: +201001588300; Email: mizosherbini@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 38 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Pregnant women candidate for LSCS.
• Age: 20-40 years old.
• Full term pregnancies (> 37 weeks confirmed by the 1st day of the LMP or 1st trimesteric ultrasound scan).
• Singleton or twin pregnancies.
• Maternal Anemia (hemoglobin < 9.9 g%)
• Maternal medical disorders (e.g. cardiac, renal, and hepatic diseases, Thromboembolic disorders or coagulopathies).
• High risk case for obstetric hemorrhage (e.g. peripartum hemorrhage, accidental hemorrhage, placenta previa, previous history of uterine atony or postpartum hemorrhage).
• CS under spinal anesthesia.

Exclusion Criteria:

• Fetal death (IUFD).
• Fetal anomalies or IUGR (estimated fetal weight below the 5th centile)
• Women attending for emergency CS.
• More than 2 previous CS procedures.
• Prolonged procedure (more than 2 hours from skin incision to skin closure).
• History of prostaglandin or Tranexamic acid allergy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Tranexamic group; 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).	Drug: Tranexamic acid; 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) (n=115); Other Names: Kapron
Active Comparator: Misoprostol group; patients will be given 400 microgram misoprostol (2 tablets - Cytotec, Pfizer, G.D. Searle LLC) sublingually immediately before starting skin incision.	Drug: Misoprostol; patients will be given 400 microgram misoprostol (2 tablets - Cytotec, Pfizer, G.D. Searle LLC) sublingually immediately before starting skin incision (n=115); Other Names: Cytotec
Active Comparator: oxytocin only group; patients will receive an intravenous bolus of 5 IU oxytocin (Syntocinon, Novartis, Basel, Switzerland) and 20 IU oxytocin in 500 mL lactated Ringer's solution (infused at a rate of 125 mL/h) following the delivery of the baby	Drug: Oxytocin; patients will receive an intravenous bolus of 5 IU oxytocin (Syntocinon, Novartis, Basel, Switzerland) and 20 IU oxytocin in 500 mL lactated Ringer's solution (infused at a rate of 125 mL/h) following the delivery of the baby (n=115); Other Names: syntocinone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
o compare the estimated blood loss (EBL) during cesarean delivery among the three groups	Estimated Blood Loss (EBL) will be evaluated as follows: A. The number of operative towels used. B. 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). C. EBL calculation according to the following formula: EBL= EBV x [(Preoperative hematocrit- Postoperative hematocrit)/ Postoperative hematocrit]	Intraoperative and within the first 24 hours postoperative.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Use of additional ecbolics denoting uterine atony	5 IU intravenous bolus oxytocin and 1mL [0.2 mg] intramuscular ergometrine with or without 600 microgram rectal misoprostol postoperatively).	within 24 hours postpartum
The occurrence of Excessive blood loss will be documented	Excessive blood loss (> 1000 mL) and the need for blood transfusion will be documented	within the first 24 hours postoperatively

Collaborators and Investigators

• Sponsor: Cairo University
• Investigators: Principal Investigator: Moutaz Elsherbini, MD, assistant professor

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2020
• Primary Completion (Anticipated): October 1, 2020
• Study Completion (Anticipated): November 1, 2020

Study Registration Dates

• First Submitted: October 3, 2019
• First Submitted That Met QC Criteria: October 3, 2019
• First Posted (Actual): October 7, 2019

Study Record Updates

• Last Update Posted (Actual): January 31, 2020
• Last Update Submitted That Met QC Criteria: January 30, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: tranexamic acid; misoprostol; high risk pregnancy
• Additional Relevant MeSH Terms: Pathologic Processes; Pregnancy Complications; Obstetric Labor Complications; Puerperal Disorders; Uterine Hemorrhage; Hemorrhage; Postpartum 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
• Other Study ID Numbers: 280391 (Other Identifier: IRAS)

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
• product manufactured in and exported from the U.S.: No