Postpartum hemorrhage reduction with oral tranexamic acid (PROTECT): a multicenter randomized controlled trial

Aim: To evaluate the effect of oral tranexamic acid (TA) compared to placebo on postpartum hemorrhage (PPH) ≥500ml in vaginal deliveries.Project design: Multicenter 2-armed double-blinded randomized controlled trial Jan 2022-Dec 2025.Population: Women ≥18-years (n=1000) with vaginal delivery ≥36 gestational weeks at 5 study sites in Sweden and South Africa.

Exclusion criteria are bleeding disorders,TA hypersensitivity, or ongoing treatment/heredity for thromboembolic disorder.Intervention: Recruitment will occur at an antenatal visit. We will randomize women in active labor to receive oral TA (n=500) or placebo (n=500).

TA dose (1g or 2 g) and timing of intake (at delivery or ∼2 hours before delivery) will be determined by our pilot study (DNR 2019-06121).Control group: Women receiving placeboOutcomes: Primary :1) Weight-assessed PPH ≥500ml, 2) PPH ≥500ml based on a pre-postpartal hemoglobin difference (g/L) ≥10 unitsSecondary: 3) Severe PPH (≥1000ml), 4) Blood transfusion, 5) Mean blood loss (ml), 6) Feasibility, 7) ThromboembolismAnalysis: The study is sized to show a minimum 9% decrease in rate of PPH ≥500ml (from a baseline rate of 39% to 30%) with 80% power and 95% confidence, assuming a 10% discontinuation rate.

Main outcome data will be compared using 2-sided Chi-square tests. Blood loss will be assessed as gemometric mean using Student´s T-test. Groups wills be compared according to intention to treat allocation and per protocol.