Tranexamic Acid Plus Buccal Misoprostol on Blood Loss During and After Cesarean Delivery

The Effect of IV Tranexamic Acid Plus Buccal Misoprostol on Blood Loss During and After Cesarean Delivery: a Randomized Controlled Trial

Postpartum hemorrhage (PPH) is potentially life-threatening and is a significant contributor to maternal mortality and morbidity especially in developing countries.

The risk of PPH is much higher for women undergoing cesarean delivery (CD). In the majority of cases, uterine atony is responsible for the occurrence of excessive bleeding during or following childbirth.

The Millennium Development Goal of reducing the maternal mortality ratio by 75 % by 2015 will remain beyond our reach unless we prioritize the prevention and treatment of PPH in low-resource countries.

Consequently, the administration of uterotonic drugs during cesarean section (CS) and in the third stage of labor for vaginal delivery has become essential to diminish the risk of PPH and improve maternal safety.

Oxytocin is regarded as the gold standard uterotonic agent but only has a half-life of 4-10 min; therefore, at cesarean section oxytocin must be administered as a continuous intravenous infusion to attain sustained uterotonic activity throughout the surgical procedure and immediate postpartum period.

Misoprostol is a prostaglandin E1 analog proven in several randomized controlled trials to be effective in preventing PPH because of its strong uterotonic effects. In addition, misoprostol is inexpensive, stable at room temperature, and easy to administer.

Misoprostol has been broadly studied in the prevention and treatment of PPH after vaginal delivery; however, its use in conjunction with CD has not been investigated as much.

The buccal route is recognized as having the greatest benefit due to its rapid uptake, long-acting effect, and greatest bioavailability compared with other routes of misoprostol administration.

Tranexamic acid(TA) 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 analog; ε-aminocaproic acid.

The aim of this study was to compare the effectiveness of combined buccal misoprostol and intravenous TA with intravenous oxytocin for the prevention of PPH in patients with risk factors during cesarean section.

Study Overview

• Status: Completed
• Conditions: Cesarean Section Complications
• Intervention / Treatment: Drug: Oxytocin; Drug: Tranexamic acid plus misoprostol; Drug: misoprostol

Detailed Description

Eligible and consenting participants were randomized via a computer-generated random number sequence into one of two groups: one group received a pre-prepared sealed and opaque packet containing 400 μg of misoprostol (2 tablets of 200 μg), 2 ampoules of TA (1 gm for infusion) and separate placebo ampoule (distilled water). The other group received similar packets containing two placebo tablets, two placebo ampoules (distilled water) and separate 2 ampoules of oxytocin (10 IU in each ampoule for infusion) for slow intravenous injection. The misoprostol and placebo tablets were similar in size, shape, and color, and ampoules of oxytocin will be also similar to placebo. Randomization was done by the investigator immediately before transfer to the theater, whereas the preparation of packets and confidential record maintenance was done by the labor room nursing staff.

Study drug administration 400 μg misoprostol (2 tablets of 200 μg) or two placebo tablets were given buccally after spinal anesthesia and few minutes before skin incision; then 1 gm TA or separate placebo will be diluted in 100 mL normal saline and administered slowly (over 30-60 s) intravenously before skin incision, in group 2 20 IU oxytocin or placebo ampoules in 500 mL of intravenous solution infusion over 15 min after delivery of baby.

• Study Type: Interventional
• Enrollment (Actual): 400
• Phase: Not Applicable

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:

• patients scheduled for an elective cesarean section with risk factors for atonic PPH

Exclusion Criteria:

• Patients with a cardiac, hepatic, renal or thromboembolic disease
• patients had an allergy to tranexamic acid
• suspected coagulopathy
• history of coronary artery disease or hypertension
• patient refuses to participate

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: oxytocin; 20 IU oxytocin ampoules in 500 mL of intravenous solution infusion over 15 min after delivery of the baby.plus 2tab placebo buccal(ranitidine) plus 110 ml saline iv	Drug: Oxytocin; 20 IU oxytocin or placebo ampoules in 500 mL of intravenous solution infusion over 15 min after delivery of the baby.plus 2tab placebo buccal plus 110 ml saline by slow infusion; Other Names: Active Comparator
Active Comparator: Tranexamic acid plus misoprostol; 400 μg misoprostol (2 tablets of 200 μg) or two placebo tablets were given buccally after spinal anesthesia and few minutes before skin incision; then 1 gm TA will be diluted in 100 mL normal saline and administered slowly (over 30-60 s) intravenously by the anesthetist before skin incision, plus 500 ml normal saline intravenous solution infusion over 15 min after delivery of the baby	Drug: Tranexamic acid plus misoprostol; 1 gm TA or separate placebo will be diluted in 100 mL normal saline and administered slowly (over 30-60 s) intravenously by the anesthetist before skin incision,; Other Names: Active Comparator; Drug: misoprostol; 400 μg misoprostol (2 tablets of 200 μg) will be give buccally after spinal anesthesia and few minutes before skin incision; Other Names: Active Comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
number of participant required of additional pharmacological uterotonic.	the number of participant need for extra uterotonic drug	24 hours post operative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
difference between preoperative and postoperative hemoglobin	compare of hemoglobin in gm/dl preoperative and 24 hours post operative	24 hours post operative
intraoperative blood loss	amount of blood loss during the operation	during the operation
post operative blood loss	amount of blood loss from the end of operation till 24 hours post operative	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 31, 2020
• Study Completion (Actual): June 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): July 14, 2020
• Last Update Submitted That Met QC Criteria: July 12, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: cesarean section; tranexamic acid; postpartum hemorrhage; buccal misoprostol
• Additional Relevant MeSH Terms: Pathologic Processes; 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: aswu/173/7/18

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