TRAAP2 - TRAnexamic Acid for Preventing postpartum hemorrhage after cesarean delivery: a multicenter randomized, doubleblind, placebo- controlled trial - a study protocol

Abstract

Background: An antifibrinolytic agent that blocks lysine-binding sites on plasminogen molecules, tranexamic acid reduces bleeding-related mortality in women with postpartum hemorrhage (PPH), especially administered fairly soon after delivery. According to the randomized controlled trials thus far reported for PPH prevention after cesarean deliveries (n = 16), women who received tranexamic acid had significantly less postpartum blood loss and no increase in severe adverse effects. These were, however, primarily small single-center studies that had fundamental methodological flaws. Multicenter randomized controlled trials with adequate power are necessary to demonstrate its value persuasively before tranexamic acid goes into widespread use for the prevention of PPH after cesarean deliveries.

Methods/design: This study will be a multicenter, double-blind, randomized controlled trial with two parallel groups including 4524 women with cesarean deliveries before or during labor, at a term ≥34 weeks, modeled on our previous study of tranexamic acid administered after vaginal deliveries. Treatment (either tranexamic acid 1 g or placebo) will be administered intravenously just after birth. All women will also receive a prophylactic uterotonic agent. The primary outcome will be the incidence of PPH, defined by a calculated estimated blood loss > 1000 mL or a red blood cell transfusion before day 2 postpartum. This study will have 80% power to show a 20% reduction in the incidence of PPH, from 15.0 to 12.0%.

Discussion: As an, inexpensive, easy to administer drug that can be add to the routine management of cesarean births in delivery rooms, tranexamic acid is a promising candidate for preventing PPH after these births. This large, adequately powered, multicenter randomized placebo-controlled trial seeks to determine if the benefits of the routine prophylactic use of tranexamic acid after cesarean delivery significantly outweigh its risks.

Trial registration: ClinicalTrials.gov NCT03431805 (February 12, 2018).

Keywords: Cesarean and vaginal deliveries; Postpartum hemorrhage; Prevention; Randomized trial; Thrombosis; Tranexamic acid; Treatment.