TRAnexamic acid in hemorrhagic CESarean ...
Type de document :
Article dans une revue scientifique
PMID :
URL permanente :
Titre :
TRAnexamic acid in hemorrhagic CESarean section (TRACES) randomized placebo controlled dose-ranging pharmacobiological ancillary trial: study protocol for a randomized controlled trial
Auteur(s) :
Ducloy-Bouthors, Anne-Sophie [Auteur]
Jeanpierre, Emmanuelle [Auteur]
Saidi, Imen [Auteur]
Baptiste, Anne-Sophie [Auteur]
Simon, Elodie [Auteur]
LANNOY, Damien [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 [GRITA]
Duhamel, Alain [Auteur]
Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS]
Allorge, Delphine [Auteur]
Impact de l'environnement chimique sur la santé humaine - ULR 4483 [IMPECS]
Susen, Sophie [Auteur]
Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD]
Hennart, Benjamin [Auteur]
Jeanpierre, Emmanuelle [Auteur]
Saidi, Imen [Auteur]
Baptiste, Anne-Sophie [Auteur]
Simon, Elodie [Auteur]
LANNOY, Damien [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 [GRITA]
Duhamel, Alain [Auteur]
Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS]
Allorge, Delphine [Auteur]
Impact de l'environnement chimique sur la santé humaine - ULR 4483 [IMPECS]
Susen, Sophie [Auteur]
Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD]
Hennart, Benjamin [Auteur]
Titre de la revue :
Trials
Nom court de la revue :
Trials
Numéro :
19
Pagination :
149
Date de publication :
2018-03-01
ISSN :
1745-6215
Mot(s)-clé(s) :
Cesarean section
D-dimers
Fibrinolysis
Pharmacokinetics
Plasmin
Postpartum hemorrhage
Tranexamic acid
D-dimers
Fibrinolysis
Pharmacokinetics
Plasmin
Postpartum hemorrhage
Tranexamic acid
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Résumé :
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 ...
Lire la suite >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: ClinicalTrials.gov, NCT02797119. Registered on 13 June 2016.Lire moins >
Lire la suite >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: ClinicalTrials.gov, NCT02797119. Registered on 13 June 2016.Lire moins >
Langue :
Anglais
Audience :
Internationale
Vulgarisation :
Non
Établissement(s) :
Université de Lille
CHU Lille
Institut Pasteur de Lille
Inserm
CHU Lille
Institut Pasteur de Lille
Inserm
Collections :
- Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - ULR 7365
- IMPact de l'Environnement Chimique sur la Santé humaine (IMPECS) - ULR 4483
- METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694
- Récepteurs nucléaires, Maladies Cardiovasculaires et Diabète (RNMCD) - U1011
Équipe(s) de recherche :
Modélisation biopharmaceutique et pharmacocinétique
Date de dépôt :
2019-02-26T17:11:38Z