Therapeutic and pharmaco-biological, dose-ranging multicentre trial to determine the optimal dose of TRAnexamic acid to reduce blood loss in haemorrhagic CESarean delivery (TRACES): study protocol for a randomised, double-blind, placebo-controlled trial

Abstract

BackgroundPostpartum haemorrhage (PPH) is the leading cause of maternal death worldwide. Tranexamic acid (TA), an antifibrinolytic drug, reduces bleeding and transfusion need in major surgery and trauma. In ongoing PPH following vaginal delivery, a high dose of TA decreases PPH volume and duration, as well as maternal morbidity, while early fibrinolysis is inhibited. In a large international trial, a TA single dose reduced mortality due to bleeding but not the hysterectomy rate. TA therapeutic dosages vary from 2.5 to 100 mg/kg and seizures, visual disturbances and nausea are observed with the highest dosages. TA efficiency and optimal dosage in haemorrhagic caesarean section (CS) has not been yet determined. We hypothesise large variations in fibrinolytic activity during haemorrhagic caesarean section needing targeted TA doses for clinical and biological efficacy.Methods/designThe current study proposal is a blinded, randomised controlled trial with the primary objective of determining superiority of either 1 g of TXA or 0.5 g of TXA, in comparison to placebo, in terms of 30% blood-loss reduction at 6 h after non-emergency haemorrhagic caesarean delivery (active PPH > 800 mL) and to correlate this clinical effect in a pharmacokinetics model with fibrinolysis inhibition measured by an innovative direct plasmin measurement regarding plasmatic TA concentration.A sample size of 342 subjects (114 per group) was calculated, based on the expected difference of 30% reduction of blood loss between the placebo group and the low-dose group, out of which 144 patients will be included blindly in the pharmaco-biological substudy. A non-haemorrhagic reference group will include 48 patients in order to give a reference for peak plasmin level.DiscussionTRACES trial is expected to give the first pharmacokinetics data to determinate the optimal dose of tranexamic acid to reduce blood loss and inhibit fibrinolysis in hemorrhagic cesarean section.Trial registrationClinicalTrials.gov, ID: NCT02797119. Registered on 13 June 2016.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-017-2420-7) contains supplementary material, which is available to authorized users.

Prophylactic use of tranexamic acid reduces blood loss and transfusion requirements in patients undergoing cesarean section: A meta‐analysis

“…Among these, four articles without sufficient data for analysis were excluded. Seven trial registrations without sufficient data for analysis were also excluded. Finally, 21 studies (19 research papers and 2 conference abstracts) with 3852 patients were eligible for our analysis.…”

Cesarean section complicated with presumed massive pulmonary embolism and cardiac arrest treated with rescue thrombolytic therapy—two case reports

“…Shakur et al in a systematic review analyzed the use of antifibrinolytic drugs in postpartum hemorrhage-so far, the risk assessment of perinatal hysterectomy has only been analyzed in the WOMEN trial (29). The TRACES trial has been registered in 2016, it plans to determine superiority of either 1 g of TXA or 0.5 g of TXA, in comparison to placebo (30).…”

Management of pregnant female with Haemophilia-A: A case report

“…Prophylactic use of Tranexamic acid in mild bleeding (1 gm IV stat then maintenance dose 1 gm over 8 hr) is to be done. [ 8 ] In selected cases desmopressin IV 0.3 mg/kg may increase FVIII concentrations and platelets, without any major side effects (mild facial flushing and headache). Mechanical thromboprophylaxis is sufficient for carriers undergoing surgeries, thromboprophylaxis with LMWH is not recommended.…”