TRAnexamic acid in hemorrhagic CESarean section (TRACES) randomized placebo controlled dose-ranging pharmacobiological ancillary trial: study protocol for a randomized controlled trial

Trials. 2018 Mar 1;19(1):149. doi: 10.1186/s13063-017-2421-6.


Background: Evidence increases that a high or a standard dose of tranexamic acid (TA) reduces postpartum bleeding. The TRACES pharmacobiological substudy aims to establish a therapeutic strategy in hemorrhagic (H) Cesarean section (CS) with respect to the intensity of fibrinolysis by using innovative assays.

Method/design: The TRACES trial is a multicenter, randomized, double-blind, placebo-controlled, TA dose-ranging study that measures simultaneously plasmatic and uterine and urine TA concentrations and the plasmin peak inhibition tested by a simultaneous thrombin plasmin generation assay described by Van Geffen (novel hemostasis assay [NHA]). Patients undergoing H CS (>800 mL) will receive blindly TA 0.5 g or 1 g or placebo. A non-hemorrhagic (NH) group will be recruited to establish plasmin generation profile. Venous blood will be sampled before, at the end, and then at 30, 60, 120, and 360 min after injection. Uterine bleeding will be sampled after injection. Urine will be sampled 2 h and 6 h after injection. The number of patients entered into the study will be 114 H + 48 NH out of the 390 patients of the TRACES clinical trial.

Discussion: To explore the two innovative assays, a preliminary pilot study was conducted. Blood samples were performed repeatedly in patients undergoing either a H (>800 mL) or NH (<800 mL) CS and in non-pregnant women (NP). H patients received TA (0-2 g). Dose-dependent TA plasmatic concentrations were determined by LC-MS/MS quantification. Plasmin generation and its inhibition were tested in vitro and in vivo using the simultaneous thrombin-plasmin generation assay (STPGA). The pilot study included 15 patients in the H group, ten patients in the NH group, and seven patients in the NP group. TA plasmatic concentration showed a dose-dependent variation. STPGA inter-assay variation coefficients were < 20% for all plasmin parameters. Inter-individual dispersion of plasmin generation capacity was higher in H and NH groups than in NP group. Profile evolution over time was different between groups. This preliminary technical validation study allows TRACES pharmacobiological trial to be conducted.

Trial registration:, NCT02797119. Registered on 13 June 2016.

Keywords: Cesarean section; D-dimers; Fibrinolysis; Pharmacokinetics; Plasmin; Postpartum hemorrhage; Tranexamic acid.

Publication types

  • Clinical Trial Protocol

MeSH terms

  • Antifibrinolytic Agents / administration & dosage*
  • Antifibrinolytic Agents / adverse effects
  • Antifibrinolytic Agents / pharmacokinetics
  • Biomarkers / blood
  • Blood Loss, Surgical / prevention & control*
  • Cesarean Section / adverse effects*
  • Double-Blind Method
  • Drug Dosage Calculations
  • Drug Monitoring / methods
  • Female
  • Fibrin Fibrinogen Degradation Products / metabolism
  • Fibrinolysin / metabolism
  • Fibrinolysis / drug effects*
  • France
  • Humans
  • Multicenter Studies as Topic
  • Pilot Projects
  • Postpartum Hemorrhage / blood
  • Postpartum Hemorrhage / diagnosis
  • Postpartum Hemorrhage / prevention & control*
  • Pregnancy
  • Preliminary Data
  • Randomized Controlled Trials as Topic
  • Time Factors
  • Tranexamic Acid / administration & dosage*
  • Tranexamic Acid / adverse effects
  • Tranexamic Acid / pharmacokinetics
  • Treatment Outcome


  • Antifibrinolytic Agents
  • Biomarkers
  • Fibrin Fibrinogen Degradation Products
  • fibrin fragment D
  • Tranexamic Acid
  • Fibrinolysin

Associated data