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

ABSTRACT: 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?

SUBMITTER: Ducloy-Bouthors AS

PROVIDER: S-EPMC5831219 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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

Ducloy-Bouthors Anne-Sophie AS Jeanpierre Emmanuelle E Saidi Imen I Baptiste Anne-Sophie AS Simon Elodie E Lannoy Damien D Duhamel Alain A Allorge Delphine D Susen Sophie S Hennart Benjamin B

Trials 20180301 1

<h4>Background</h4>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.<h4>Method/design</h4>The TRACES trial is a multicenter, randomized, double-blind, placebo-controlled, TA dose-ranging study that measures simultaneously plasmatic and uterine and urin ...[more]

PMID: 29490690

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Project description:BACKGROUND:Postpartum 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/DESIGN:The 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. DISCUSSION:TRACES 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 REGISTRATION:ClinicalTrials.gov, ID: NCT02797119 . Registered on 13 June 2016.

Project description:BackgroundLoss of resistance (LOR) technique is a widely used method to identify the epidural space. However, cases of inadequate epidural anesthesia in cesarean section were frequently reported. Also, the success rate of epidural anesthesia with LOR technique varied depending on the proficiency of the practitioner. The purpose of this study was to assess the efficacy and safety of electrical stimulation to identify epidural spaces in cesarean section for novices or clinicians with recent gap in experience.MethodsPregnant women scheduled for elective cesarean section were randomly allocated to two groups. Groups were classified based on the methods used for identifying the epidural space: the LOR group (group L) and the LOR with epidural electrical stimulation group (group E). Clinicians with less than 10 epidural cesarean section experiences in the recent year performed epidural anesthesia for cesarean section. In the group E, a RegionalStim® conductive catheter was inserted through the Tuohy needle, and the guidewire passing through the catheter was connected to a peripheral nerve stimulator. The intensity of the stimulation was gradually increased from 0.25 mA to 1.5 mA until paresthesia was elicited and radiated. We assessed the success of epidural anesthesia (complete success, partial success or failure). Other clinical parameters including maternal satisfaction, time required for epidural anesthesia, neonatal Apgar scores, pain scores and adverse events were compared between the two groups.ResultsExcept for 6 patients who withdrew consent, 54 patients were enrolled in this study (28 for the group L and 26 for the group E). The demographic data showed no difference between the two groups. There was no adverse event resulted from electrical stimulation. The group E showed higher rate of complete success, sensitivity in finding epidural space and maternal satisfaction compared to the group L (21/26 vs. 15/28, p = 0.034, 0.96 vs. 0.68, p = 0.012 and 4.04 vs. 3.39, p = 0.02, respectively). The other clinical parameters showed no differences between the two groups.ConclusionIn addition to the conventional LOR technique, identifying epidural spaces using electrical stimulation led to better outcomes without additional risks for novices as well as clinicians with recent gap in experience.Trial registrationThis study was retrospectively registered in the ClinicalTrials.gov Registry (NCT03443466) on February 23, 2018.

Project description:BackgroundAnticoagulant therapy during pregnancy is widely used due to the increasing awareness of maternal hypercoagulability. Few studies have reported the use of minimally invasive spinal anesthesia in these parturients. The objective of this study was to evaluate the safety and feasibility of minimally invasive spinal anesthesia in parturients with anticoagulation therapy undergoing cesarean section.MethodsThis was a randomized, controlled study conducted in 239 parturients using anticoagulants and undergoing selective cesarean section. 37 parturients withdrew, and finally parturients received spinal anesthesia using 27gauge pen type fine spinal needles (experimental group, n = 110) and 22gauge traditional spinal needles (control group, n = 92). The primary efficacy outcomes included low back pain (LBP) and postdural puncture headache (PDPH) after delivery. Secondary efficacy outcomes included visual analogue scale during subarachnoid puncture (VASdural), difference between visual analogue scale (VAS) during peripheral venipuncture and VASdural (∆VAS), VAS of back puncture point 24, 48 and 72 h after operation (VASdural-24 h, VASdural-48 h and VASdural-72 h, respectively), maternal satisfaction and hospitalization stay.ResultsNo parturient had PDPH and was suspected with spinal or intracranial haematoma in two groups. There was no significant difference in VASlbp-24 h, VASlbp-48 h and VASlbp-72 h (P = 0.056; P = 0.813; P = 0.189, respectively) between two groups. In experimental group, VASdural (P = 0.017), ∆VAS (P = 0.001) and VASdural-24 h (P < 0.0001) were lower, whereas maternal satisfaction was higher (P = 0.046). There was no significant difference in VASdural-48 h, VASdural-72 h, urination function, strength recovery and hospitalization stay (P = 0.069; P = 0.667; P = 0.105; P = 0.133; P = 0.754, respectively) between the two groups.ConclusionsMinimally invasive spinal anesthesia provided lower VASdural, VASdrual-24 h and a higher maternal satisfaction. Hence, it is considered as a safe, reliable and reasonable option for cesarean section parturients during maternal anticoagulation therapy with normal platelet count and coagulation time.Trial registrationThis study was registered at www.ClinicalTrials.gov at November 11th, 2016 ( NCT02987192 ).

Dataset Information

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

Publications

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

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