出血性剖宫产术中氨甲环酸（TRACES）随机安慰剂对照剂量范围药物生物学辅助试验：一项随机对照试验的研究方案
TRAnexamic acid in hemorrhagic CESarean section (TRACES) randomized placebo controlled dose-ranging pharmacobiological ancillary trial: study protocol for a randomized controlled trial.
作者信息
Ducloy-Bouthors Anne-Sophie, Jeanpierre Emmanuelle, Saidi Imen, Baptiste Anne-Sophie, Simon Elodie, Lannoy Damien, Duhamel Alain, Allorge Delphine, Susen Sophie, Hennart Benjamin
机构信息
Pole anesthésie réanimation, maternité Jeanne de Flandre, centre hospitalier regional et universitaire, 2 avenue Oscar Lambret, 59037, Lille, France.
Laboratoire d'hémostase-hémobiologie, centre biologie pathologie, centre hospitalier regional et universitaire, 2 avenue Oscar Lambret, 59037, Lille, France.
出版信息
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
ClinicalTrials.gov, NCT02797119. Registered on 13 June 2016.
背景
越来越多的证据表明，高剂量或标准剂量的氨甲环酸（TA）可减少产后出血。TRACES药物生物学子研究旨在通过使用创新检测方法，针对出血性（H）剖宫产（CS）制定基于纤维蛋白溶解强度的治疗策略。
方法/设计：TRACES试验是一项多中心、随机、双盲、安慰剂对照的TA剂量范围研究，同时测量血浆、子宫和尿液中的TA浓度以及通过Van Geffen描述的同时凝血酶-纤溶酶生成试验（新型止血试验[NHA]）检测的纤溶酶峰值抑制情况。接受H CS（>800 mL）的患者将被盲法给予0.5 g或1 g TA或安慰剂。将招募一个非出血性（NH）组以确定纤溶酶生成情况。在注射前、结束时以及注射后30、60、120和360分钟采集静脉血。注射后采集子宫出血样本。注射后2小时和6小时采集尿液样本。TRACES临床试验的390名患者中，将有114名H患者+48名NH患者纳入本研究。
讨论
为探索这两种创新检测方法，进行了一项初步的预试验研究。对接受H（>800 mL）或NH（<800 mL）CS的患者以及非孕妇（NP）反复采集血样。H组患者接受TA（0 - 2 g）。通过液相色谱-串联质谱（LC-MS/MS）定量测定TA血浆浓度的剂量依赖性。使用同时凝血酶-纤溶酶生成试验（STPGA）在体外和体内检测纤溶酶生成及其抑制情况。预试验研究包括15名H组患者、10名NH组患者和7名NP组患者。TA血浆浓度呈现剂量依赖性变化。所有纤溶酶参数的STPGA批间变异系数<20%。H组和NH组纤溶酶生成能力的个体间离散度高于NP组。各组随时间的变化情况不同。这项初步的技术验证研究使得TRACES药物生物学试验得以开展。
试验注册
ClinicalTrials.gov，NCT02797119。于2016年6月13日注册。
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