Investigating the efficacy of tranexamic acid (TXA) as a prophylactic agent in reducing postpartum haemorrhage (PPH) among patients undergoing cesarean section (CS) in SQUH: a prospective randomized controlled trial.

To evaluate the efficacy of tranexamic acid (TXA) in reducing blood loss during elective and emergency caesarean sections in comparison to placebo. Research methodology, A Prospective, double blinded, randomized - control trial.

Tranexamic acid has been found to be an effective drug and is recommended in the management of post partum haemorrhage. However there are limited studies in its use as a prophylactic agent in the prevention of post partum haemorrhage.

Introduction

Postpartum haemorrhage (PPH) remains a leading cause of maternal morbidity and mortality worldwide, accounting for nearly one-quarter of all maternal deaths. Caesarean section (CS), while a life-saving procedure, is associated with an increased risk of PPH compared to vaginal delivery. Haemorrhage following CS is most commonly due to uterine atony, where ineffective uterine contraction after delivery leads to excessive bleeding.

Additional contributors include surgical trauma, retained placental tissue, and coagulation disorders.

The risk is particularly elevated in emergency CS, where prolonged labour, infection, and compromised uterine contractility further impair haemostasis.

Preventive interventions for PPH traditionally rely on the administration of uterotonic agents such as oxytocin, ergometrine, and prostaglandins. Despite the availability of preventive interventions, continued advances in PPH management are critical, especially the identification of safe, effective, and cost-efficient measures. Antifibrinolytic therapy with tranexamic acid (TXA), which inhibits fibrinolysis and stabilizes clot formation, has emerged as a promising adjunct. TXA has been widely used across medical and surgical specialties, including trauma care, where the CRASH-2 trial demonstrated its efficacy in reducing mortality from bleeding, with the greatest benefit achieved when administered early.

In obstetric practice, TXA has shown favourable results in both vaginal and caesarean deliveries. A Cochrane review including 3,285 women concluded that prophylactic TXA, in addition to standard uterotonics, reduces postpartum blood loss, prevents PPH, and decreases the need for blood transfusion. Specifically, in CS, randomized controlled trials have consistently demonstrated its efficacy in reducing intraoperative and postoperative blood loss, with a favourable safety profile. Importantly, its integration into routine clinical care could be particularly beneficial in resourcelimited settings where access to blood products is constrained.

Although some international evidence supports the prophylactic use of TXA to reduce PPH following CS, there is a paucity of region-specific data. In Oman, the safety and effectiveness of TXA as a preventive strategy in caesarean births have not yet been studied. Generating local evidence is therefore essential to guide clinical practice and improve maternal outcomes.

The latest guidelines on postpartum hemorrhage in 2025 for the prevention, diagnosis and treatment of postpartum hemorrhage by World Health Organization (WHO) and International Federation of the Obstetrics and Gynecology, FIGO has recommended it as a treatment and not for prophylaxis.

Aim of the Study To evaluate the efficacy of tranexamic acid (TXA) in reducing blood loss during elective and emergency caesarean sections in comparison to placebo.

Hypothesis: Tranexamic acid is effective in reducing the incidence of PPH when used as prophylaxis in patients at high risk of PPH.

Research Methodology Prospective, double blinded, randomized - control trial.

Study Design and Setting This is a Prospective, double blinded, randomized - control trial to be conducted at Sultan Qaboos University Hospital (SQUH) in Muscat, Oman. Pregnant woman undergoing elective or emergency caesarean section at & > 34 weeks of gestation, in Sultan Qaboos university hospital.

Primary Outcomes are measured blood loss from skin incision to 24 hours postpartum using calibrated drapes (intra-op) + gravimetric method (pads/linens) and suction canister accounting for irrigation, and Incidence of PPH ≥1000 mL within 24 hours after CS.

Key Secondary Outcomes include drop in haemoglobin (g/dL) from preoperative (≤24 h prior) to 24-48 hours postoperative, proportion requiring blood transfusion (any PRBC) and number of units transfused, and need for additional uterotonics and surgical hemostatic interventions (e.g., B-Lynch, uterine artery ligation, balloon tamponade, hysterectomy).

Study Period between May 2026 to December 2027

Data collection Woman eligible for the study will be identified during antenatal visits or on admission for CS and written informed consent will be obtained.

Sample size: The sample size was estimated based on the anticipated incidence proportion of postpartum haemorrhage (PPH) in the two arms of the randomized controlled trial (Tranexamic Acid [TXA] group vs. Placebo group). Based on a review of previously published studies, we anticipated an incidence proportion of 10% for PPH in the TXA group and 40% in the placebo group, corresponding to an expected risk ratio (effect size) of 0.25. The significance level was set at 5%, and the power at 80%, with an allocation ratio of 1:1. Accounting for an expected attrition rate of 10%, the final sample size was calculated to be 88 participants (44 in each arm). The calculation was performed using OpenEpi software.

Block randomization was performed to allocate participants equally into Group A and Group B, usingvariable block sizes of 4, 6, and 8 to maintain balance and reduce allocation predictability. A total sample of 88 participants was planned, with 44 participants in each group. The randomization sequence was generated using the online randomization tool available at sealedenvepe.com, ensuring concealment and reproducibility. Within each block, participants were randomly assigned to either Group A or Group B in equal proportions, maintaining overall balance throughout the recruitment process while preventing selection bias due to varying block sizes.

Inclusion Criteria • Pregnant woman with risk factors for postpartum haemorrhage undergoing elective and emergency caesarean section in SQUH. Risk factors for postpartum haemorrhage include previous CS, multiple pregnancy, polyhydramnios, foetal macrosomia (BW >4kg), anemia, booking BMI>30, previous history of PPH, fibroids, adenomyosis, placenta previa (non- accreta), chorioamnionitis.

Exclusion Criteria • Woman with condition like Placenta accreta spectrum, contraindications to tranexamic acid (e.g., hypersensitivity to tranexamic acid), history of seizure disorders, kidney disease, thromboembolic disease, or medical conditions or treatments associated with a high risk of thrombosis will be excluded from the study

Withdrawal criteria: If the patient withdraws her consent or if there arises a need to unmask the drug, the patient will be withdrawn from the study.

Quality control and quality assurance: will be maintained by the pharmacist, surgeons and anaesthesia staff involved to ensure blinding and administration of the drug at the time of skin incision.

Intervention Woman eligible for the study will be identified during antenatal visits or on admission for CS and written informed consent will be obtained. TXA will be administered to women included in the study at the time of skin incision by circulating nurse. TXA will be administered as a single intravenous dose of 1g (mL). A second dose may be considered if bleeding occurs after 30 minutes or within 24 hours of the first dose. Placebo (0.9% saline) volume-matched, administered over [10 minutes], at the time of skin incision. Routine uterotonic prophylaxis will be given as per institutional protocol. Participants, surgeons/anaesthetists data collectors, and statisticians will be blinded. Emergency unblinding will be permitted only if knowledge of allocation is essential for clinical care.

Results: Continuous variables will be summarized using the mean, median, and standard deviation, while categorical variables will be described as frequencies and percentages. Primary and secondary outcomes will be reported as risk ratios (RRs) with 95% confidence intervals (CIs). Adjusted risk ratios, accounting for baseline risk factors for postpartum haemorrhage (PPH), will be estimated using multivariate log-binomial regression. Statistical significance will be defined as a p-value < 0.05. All analyses will be performed using IBM SPSS Statistics, version 30.0.

Inclusion Criteria:

Pregnant woman with risk factors for postpartum haemorrhage undergoing elective and emergency caesarean section in SQUH.

• Previous Caesarean Section
• Multiple pregnancy,
• Polyhydramnios,
• Fetal macrosomia (BW &gt;4kg),
• Anemia
• Booking BMI>30
• Previous history of postpartum hemorrhage
• Fibroids,
• Adenomyosis,
• Placenta previa (non- accreta),
• Chorioamnionitis.

Exclusion Criteria: Woman with conditions like

• Placenta accreta spectrum,
• Contraindications to tranexamic acid (e.g., hypersensitivity to tranexamic acid), -History of seizure disorders,
• Kidney disease,
• Thromboembolic disease,
• Medical conditions or treatments associated with a high risk of thrombosis

Female