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Is low dose Tranexamic acid less effective than a standard dose at reducing blood loss and inhibiting hyperfibrinolysis in hemorrhagic caesarean section? Multicenter double–blind placebo-controlled dose-ranging (TRACES) trial.
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  • Anne-Sophie Ducloy-Bouthors,
  • Sixtine Gilliot,
  • Maeva Kyheng,
  • David Faraoni,
  • Alexandre Turbelin,
  • Hawa Keita,
  • Agnes Rigouzzo,
  • Gabirela Moyanotidou,
  • Benjamin Constant,
  • Francoise Broisin,
  • Agnes Le-Gouez,
  • Remi Favier,
  • Edith Peynaud,
  • louise Ghesquiere,
  • Gilles Lebuffe,
  • Alain Duhamel,
  • Delphine Allorge,
  • Sophie Susen,
  • Benjamin Hennart,
  • Emmanuelle Jeanpierre,
  • Pascal Odou
Anne-Sophie Ducloy-Bouthors
Centre Hospitalier Regional Universitaire de Lille

Corresponding Author:asducloy@neuf.fr

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Sixtine Gilliot
Université Lille 2 Droit et Santé
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Maeva Kyheng
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David Faraoni
Baylor College of Medicine, Texas Children’s Hospital
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Alexandre Turbelin
Centre Hospitalier Regional Universitaire de Lille
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Hawa Keita
Assistance Publique - Hopitaux de Paris
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Agnes Rigouzzo
Assistance Publique - Hopitaux de Paris
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Gabirela Moyanotidou
Assistance Publique - Hopitaux de Paris
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Benjamin Constant
Hopital de Seclin
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Francoise Broisin
Hopital de la Croix-Rousse
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Agnes Le-Gouez
Hospital Antoine-Beclere
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Remi Favier
Assistance Publique - Hopitaux de Paris
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Edith Peynaud
Assistance Publique - Hopitaux de Paris
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louise Ghesquiere
CHU Lille Jeanne de Flandre
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Gilles Lebuffe
Université Lille 2 Droit et Santé
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Alain Duhamel
Universite Lille Nord de France
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Delphine Allorge
Centre Hospitalier Regional Universitaire de Lille
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Sophie Susen
Centre Hospitalier Regional Universitaire de Lille
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Benjamin Hennart
Centre Hospitalier Regional Universitaire de Lille
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Emmanuelle Jeanpierre
Centre Hospitalier Regional Universitaire de Lille
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Pascal Odou
Université Lille 2 Droit et Santé
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Abstract

Objective: To study the effect of a low (0.5g) or a standard (1g) tranexamic acid (TA) dose compared to placebo on clinical and biological endpoints in women experiencing postpartum hemorrhage (PPH) Design: TRACES trial is a double-blind, randomized, placebo-controlled, dose-ranging study Setting: 8 women hospitals in France. Population: Women experiencing PPH > 800 mL during caesarean section. Method: After informed consent, patients were randomized to receive either TA 0.5g (n=57), TA 1g (n=58), or a placebo (n=60). Data were collected at 8 time-points. Main outcome measures: Efficacy: additional blood loss after study drug, maternal morbidity, safety, biology: D-dimers, plasmin-antiplasmin complexes (PAP), simultaneous-generation-thrombin-plasmin-potential. Results: Compared to 1g dose, 0.5g TA was less effective to reduce additional blood loss (300 mL [95% confidence interval (95%CI) 68 to 630] vs 134 mL [95%CI50 to 419] (p=0.042)). Compared to placebo, 1g TA, but not 0.5g, inhibited hyperfibrinolysis as shown by plasmin generation potential, % increase in D-dimers from injection to 120 minutes (93% [95%CI 68 to 118] vs 58% [ 95%CI 32 to 84] (p=0.06) vs 38% [95%CI 13 to 63] (p=0.003) and % increase in PAP from injection to 30 minutes (56% [95%CI 25 to 87] vs 13% [ 95%CI 18 to 43] (p=0,051) vs -2% [95%CI -32 to 28] (p=0.009)). Conclusions: In this study, fibrinolysis inhibition was more sustained after the administration of 1g TA compared to 0.5g TA or a placebo. Further pharmacokinetic-pharmacodynamic modelling will be needed to determine the optimal TA dose to be administered in PPH. NCT 02797119
01 Nov 2021Submitted to BJOG: An International Journal of Obstetrics and Gynaecology
01 Nov 2021Submission Checks Completed
01 Nov 2021Assigned to Editor
02 Nov 2021Reviewer(s) Assigned
31 Dec 2021Review(s) Completed, Editorial Evaluation Pending