title: Study protocol. TRAAP - TRAnexamic Acid for Preventing postpartum hemorrhage after vaginal delivery: a multicenter randomized, double-blind, placebo-controlled trial.
abstract: BACKGROUND
  Postpartum hemorrhage (PPH) is a major cause of maternal mortality, accounting for one quarter of all maternal deaths worldwide. Estimates of its incidence in the literature vary widely, from 3 % to 15 % of deliveries. Uterotonics after birth are the only intervention that has been shown to be effective in preventing PPH. Tranexamic acid (TXA), an antifibrinolytic agent, has been investigated as a potentially useful complement to uterotonics for prevention because it has been proved to reduce blood loss in elective surgery, bleeding in trauma patients, and menstrual blood loss. Randomized controlled trials for PPH prevention after cesarean (n = 10) and vaginal (n = 2) deliveries show that women who received TXA had significantly less postpartum blood loss without any increase in their rate of severe adverse effects. However, the quality of these trials was poor and they were not designed to test the effect of TXA on the reduction of PPH incidence. Large, adequately powered, multicenter randomized controlled trials are required before the widespread use of TXA to prevent PPH can be recommended.
  
  
  METHODS
  A multicenter, double-blind, randomized controlled trial will be performed. It will involve 4000 women in labor for a planned vaginal singleton delivery, at a term ≥ 35 weeks. Treatment (either TXA 1 g or placebo) will be administered intravenously just after birth. Prophylactic oxytocin will be administered to all women. The primary outcome will be the incidence of PPH, defined by blood loss ≥500 mL, measured with a graduated collector bag. This study will have 80 % power to show a 30 % reduction in the incidence of PPH, from 10.0 % to 7.0 %.
  
  
  CONCLUSIONS
  In addition to prophylactic uterotonic administration, a complementary component of the management of third stage of labor acting on the coagulation process may be useful in preventing PPH. TXA is a promising candidate drug, inexpensive, easy to administer, and simple to add to the routine management of deliveries in hospitals. This large, adequately powered, multicenter, randomized placebo-controlled trial seeks to determine if the risk-benefit ratio favors the routine use of TXA after delivery to prevent PPH.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT02302456 (November 17, 2014).
authors.affiliation: Department of Obstetrics and Gynecology, Angers University Hospital, 4, rue Larrey, 49933, Angers, France. loicsentilhes@hotmail.com.
authors.forename: Loïc
authors.initials: L
authors.lastname: Sentilhes
authors.affiliation: Department of Pharmacy, Angers University Hospital, Angers, France. vadaniel@chu-angers.fr.|PPRIGO (Production Pharmaceutique pour la Recherche Institutionnelle du Grand Ouest) Brest University Hospital, Brest, France. vadaniel@chu-angers.fr.
authors.forename: Valérie
authors.initials: V
authors.lastname: Daniel
authors.affiliation: Department of Pharmacy, Angers University Hospital, Angers, France. asdarsonval@chu-angers.fr.|PPRIGO (Production Pharmaceutique pour la Recherche Institutionnelle du Grand Ouest) Brest University Hospital, Brest, France. asdarsonval@chu-angers.fr.
authors.forename: Astrid
authors.initials: A
authors.lastname: Darsonval
authors.affiliation: Department of Obstetrics and Gynecology, Jeanne de Flandre University Hospital, Lille, France. philippe.deruelle@univ-lille2.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Deruelle
authors.affiliation: Department of Obstetrics and Gynecology, Caen University Hospital, Caen, France. vardon-d@chu-caen.fr.
authors.forename: Delphine
authors.initials: D
authors.lastname: Vardon
authors.affiliation: Department of Obstetrics and Gynecology, Tours University Hospital, Tours, France. franck.perrotin@me.com.
authors.forename: Franck
authors.initials: F
authors.lastname: Perrotin
authors.affiliation: Port-Royal Maternity Unit, Department of Obstetrics and Gynecology, Cochin University Hospital, APHP, Paris, France. camille.leray@gmail.com.|INSERM, Obstetrical, Perinatal and Pediatric Epidemiology Research Team, Center for Epidemiology and Biostatistics (U1153), Risks in pregnancy DHU, Paris-Descartes University, Paris, France. camille.leray@gmail.com.
authors.forename: Camille
authors.initials: C
authors.lastname: Le Ray
authors.affiliation: Department of Obstetrics and Gynecology, Kremlin-Bicetre University Hospital, APHP, Paris, France. marie-victoire.senat@bct.aphp.fr.
authors.forename: Marie-Victoire
authors.initials: MV
authors.lastname: Senat
authors.affiliation: Department of Obstetrics and Gynecology, Nantes University Hospital, Nantes, France. norbert.winer@chu-nantes.fr.
authors.forename: Norbert
authors.initials: N
authors.lastname: Winer
authors.affiliation: INSERM, Obstetrical, Perinatal and Pediatric Epidemiology Research Team, Center for Epidemiology and Biostatistics (U1153), Risks in pregnancy DHU, Paris-Descartes University, Paris, France. francoise.maillard@inserm.fr.
authors.forename: Françoise
authors.initials: F
authors.lastname: Maillard
authors.affiliation: INSERM, Obstetrical, Perinatal and Pediatric Epidemiology Research Team, Center for Epidemiology and Biostatistics (U1153), Risks in pregnancy DHU, Paris-Descartes University, Paris, France. catherine.deneux-tharaux@inserm.fr.
authors.forename: Catherine
authors.initials: C
authors.lastname: Deneux-Tharaux
mesh_terms: D061605:Administration, Intravenous; D000293:Adolescent; D000328:Adult; D000933:Antifibrinolytic Agents / Q000008:administration & dosage*; D036861:Delivery, Obstetric / Q000009:adverse effects*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D015994:Incidence; D010120:Oxytocics; D010121:Oxytocin; D006473:Postpartum Hemorrhage / Q000453:epidemiology / Q000517:prevention & control*; D011247:Pregnancy; D012107:Research Design; D014148:Tranexamic Acid / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D000933:Antifibrinolytic Agents; D010120:Oxytocics; D010121:Oxytocin; D014148:Tranexamic Acid