Topical Tranexamic Acid to Reduce Blood Loss During Cesarean Delivery

Cesarean delivery carries a recognized risk of significant intraoperative bleeding despite standard uterotonic use and established surgical techniques. Tranexamic acid (TXA), an antifibrinolytic medication, reduces surgical blood loss when administered intravenously, but little is known about the effectiveness of topical TXA applied directly to the uterine incision during cesarean delivery. Evidence from other surgical fields suggests that topical TXA may reduce bleeding with minimal systemic absorption.

This study is a multi-center, randomized, placebo-controlled trial designed to evaluate whether topical TXA decreases intraoperative bleeding during elective cesarean delivery at term. A total of 112 participants will be randomized in a 1:1 ratio to receive either TXA (500 mg diluted in 15 mL saline) or an identical-appearing saline placebo. The study drug is applied by spraying the solution directly onto the uterine incision after placental delivery and before each layer of uterine closure. Randomization will be stratified by site, and allocation will be concealed using sequentially numbered envelopes opened by a scrub nurse.

All cesarean procedures will follow a standardized operative technique to minimize variability. Intraoperative and postoperative data will be collected from medical records, including operative characteristics, perioperative hemoglobin values, use of additional hemostatic measures, length of stay, and maternal or neonatal complications. Safety monitoring will focus on thromboembolic events, allergic reactions, and postoperative infections, with periodic review by an independent safety officer.

This trial aims to determine whether a localized, low-cost antifibrinolytic intervention can improve hemostasis during cesarean delivery and potentially be incorporated into routine surgical practice.

• Tranexamic Acid (Topical) (Drug), also known as Hexakapron: This intervention involves topical application of tranexamic acid (TXA) directly to the uterine incision during cesarean delivery, rather than the conventional intravenous route. A solution containing 500 mg of TXA (one ampule, 5 mL) diluted in 15 mL of normal saline is sprayed evenly over the uterine incision surface after placental delivery and before suturing. A second application of the same solution is sprayed before the second layer of uterine closure. This localized, site-directed use is designed to reduce intraoperative bleeding with minimal systemic absorption, distinguishing it from previously studied intravenous TXA regimens.
• Normal Saline (Placebo) (Other), also known as NaCl 0.9%: This comparator intervention involves topical application of sterile normal saline to the uterine incision at the same time points as in the TXA arm - after placental delivery and before each layer of uterine closure. This placebo control enables a direct comparison to determine whether the topical TXA application provides added benefit in reducing intraoperative bleeding.

Primary outcomes

• Uterine closure time (minutes) [Intraoperative (during the index cesarean delivery)]: Time from placement of the first uterine stitch to completion of the final uterine stitch including any additional hemostatic sutures (In minutes)
• Number of additional hemostatic sutures (count) [Intraoperative (during the index cesarean delivery)]: Total number of extra hemostatic stitches needed for bleeding control beyond the routine two-layer uterine closure

Secondary outcomes

• Estimated intraoperative blood loss (mL) [Intraoperative (during the index cesarean delivery)]: Blood loss estimated by the operating surgeon during the cesarean delivery, recorded at the end of the procedure using standardized estimation protocols.
• Change in hemoglobin levels [16-24 hours postoperatively]: Difference between preoperative hemoglobin concentration and hemoglobin measured 16-24 hours after surgery, expressed in g/dL.
• Need for additional uterotonic agents [Intra-operative to 24 hours postoperative]: Administration of additional uterotonic medications beyond routine prophylactic Oxycontin during surgery and up to 24 postoperative
• Need for blood transfusion [within 30 days postoperativly]: Incidence of red blood cell transfusion due to surgical blood loss or postoperative anemia.
• Duration of hospital admission (days) [Postoperative within 30 days from delivery]: Number of days from the cesarean delivery to hospital discharge.
• Postoperative complications [Up to 30 days after surgery]: Occurrence of any postoperative maternal complications, including fever, endometritis, wound infection, thromboembolic events, or reoperation
• Post-discharge emergency department visits or hospital readmissions [Within 30 days postpartum]: Any maternal emergency department visits or readmissions related to the delivery within one month of cesarean section.

Sex: Female, ages: 18 Years to 51 Years, accepts healthy volunteers

Inclusion Criteria:

* Women aged 18 to 51 years
* Singleton pregnancy
* Elective cesarean delivery scheduled at ≥37+0 weeks of gestation
* First or second cesarean delivery only
* Low transverse uterine incision planned
* Double-layer uterine closure using 1-0 Vicryl sutures
* Ability to provide written informed consent

Exclusion Criteria:

* Known allergy or hypersensitivity to tranexamic acid (TXA)
* History of bleeding or coagulation disorders
* Previous postpartum hemorrhage
* Placenta previa or placenta accreta spectrum
* Presence of uterine myomas
* Current use of anticoagulant or antiplatelet medications
* Planned or intraoperative conversion to general anesthesia
* Known uterine malformations
* Known bleeding tendency or thromboembolic disease

• Amichai Rottenstreich, Principal investigator, Edith Wolfson Medical center