Tranexamic Acid to Reduce Blood Loss in Hemorrhagic Caesarean Delivery: a Multicenter Randomized Double Blind Placebo Controlled Therapeutic and Pharmaco-biological Dose Ranging Study (TRACES) for Its Optimal Benefit/Risk
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 225
- 试验地点
- 5
- 主要终点
- Bleeding
研究概览
简要总结
TRACES trial is a multicenter randomized double blind placebo control therapeutic and pharmaco-biological dose ranging study to measure the effect on blood loss reduction of a single intravenous infusion of two doses regimens (standard dose and low dose) of TA administered at the onset of an active PPH (>800mL) during elective or non-emergent CS and to correlate this clinical effect with the biological effect of fibrinolysis inhibition and the pharmacodynamic measure of TA uterine bleeding and venous blood concentration.
详细描述
Postpartum hemorrhage (PPH) is the leading cause of maternal death. Tranexamic acid (TA) (Exacyl® Sanofi France), an antifibrinolytic drug, reduces bleeding and transfusion need in major surgery and trauma (1). In ongoing PPH following vaginal delivery (2), a high dose of TA decreased the volume and duration of PPH, the transfusion need and the maternal morbidity, while early fibrinolysis was inhibited (3). Prophylactic use of TA limited the postoperative bleeding in elective non hemorrhagic caesarean section (CS). (1, 4) TA efficiency in the hemorrhagic caesarean context has not been previously published.
TA doses range vary from 2,5 to 100 mg/kg and side effects were observed with the largest doses.(1,4) Pharmacokinetics old data concerned non hemorrhagic patients.(1) WOMAN ongoing international trial using a one gram dose have a mortality reduction objective.(5) The optimal dose for ongoing caesarean PPH has to be determined.
Aim of the study:
The aim of the multicenter randomized double blind placebo control therapeutic and pharmaco-biological dose ranging study TRACES is to measure the effect on blood loss reduction of a single intravenous infusion of two doses regimens of TA administered at the onset of an active PPH (>800mL) during elective or non-emergent CS and to correlate this clinical effect with the biological effect of fibrinolysis inhibition and the pharmacodynamic measure of TA uterine bleeding and venous blood concentration.
Statistical method:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Experimental group: Each patient
- •experiencing a bleeding volume of more than 800 mL
- •due to surgery or to atony uterine
- •during an elective or non-emergent caesarean section
- •secondary post-partum haemorrhage after caesarean section, even if CS has been emergent
- •after complete information and consent signature.
- •covered by social security. Reference non-hemorrhagic group: Each patient
- •experiencing a bleeding volume of strictly less than 800 mL
- •during an elective or emergent caesarean section
- •after complete information and consent signature.
- •covered by social security.
排除标准
- •Patient unable to consent (<18 years old or incapable people and specially protected mentioned in the article L1121-5 to L1121-8) RCP medical contraindication to tranexamic acid such as
- •Hypersensibility to the product or excipient,
- •Previous or ongoing arterial or venous thrombosis,
- •Coagulopathy, except DIC associated with a predominant fibrinolytic profile,
- •Renal failure,
- •Previous seizures,
- •intrathecal or intraventricular administration. Obstetrical contraindication to TA
- •Severe HELLP syndrome (platelet count <50 000/m3 or renal failure prior to the caesarean (RIFLE score>2) Protocol related contraindication to inclusion
- •Administration of TA before inclusion-Inherited haemorrhagic diseases and low molecular weight heparin within 24 hours before inclusion
- •Patients who participated in a study on the efficacy of an experimental drug in the two month preceding the caesarean section
- •Inherited haemorrhagic diseases or low molecular weight heparin within 24 hours before inclusion
- •Previous inclusion in an interventional trial since the 2 months before CS
研究组 & 干预措施
Saline Solution (TA0)
To measure the evolution of blood loss without TA in ongoing hemorrhagic cesarean section To correlate this clinical evolution with fibrinolysis.
干预措施: Saline Solution (TA0) (Drug)
NH
To measure the reference fibrinolytic activity in non-hemorrhagic cesarean section
tranexamic acid 0.5 g (TA1/2)
To measure the efficacy of a low 0,5g dose TA to reduce blood loss in ongoing hemorrhagic cesarean section To correlate this clinical effect with the fibrinolysis inhibition and the TA venous and uterine blood concentration
干预措施: tranexamic acid 0.5 g (TA1/2) (Drug)
tranexamic acid 1 g (TA1)
To measure the efficacy of a standard 1g dose TA to reduce blood loss in ongoing hemorrhagic cesarean section.
To correlate this clinical effect with the fibrinolysis inhibition and the TA venous and uterine blood concentration
干预措施: tranexamic acid 1 g (TA1) (Drug)
结局指标
主要结局
Bleeding
时间窗: between inclusion (T0) and 6 hours after inclusion (T360).
Bleeding will be strictly measured (mL) in aspiration or cell salvage bags (substraction of the amniotic fluid if needed) and drapes weighting at each time point.
次要结局
- number of patients presenting with maternal morbidity ie haemostatic interventions and organ failure and ICU admission(At day 5, At day 42)
- Seizures(Between T0 (inclusion) and Day 42)
- Area under the plasma concentration versus time curve (AUC) in venous blood(Between T0 (inclusion) and T360 (6hours after inclusion))
- Postpartum anemia(at day 2, at day 5)
- Postpartum blood loss(at Day 2)
- Biological fibrinolysis inhibition(Between T0 (inclusion) and T360 (6hours later))
- Deep vein thrombosis or pulmonary embolism(Between T0 (inclusion) and Day 42)
- Nausea(Between T0 (inclusion) and Day 42)
- Peak Plasma Concentration (Cmax) in uterine bleeding(Between T0 (inclusion) and T360 (6hours after inclusion))
- Death(at day 42)
- Urinary urea and Creatinuria on timed diuresis(Between T0 (inclusion) and T360 (6hours later))
- Tranexamic acid plasma concentration(Between T0 (inclusion) and T360 (6hours after inclusion))
- Tranexamic acid urinary excretion(Between T0 (inclusion) and T360 (6hours after inclusion))
- Peak Plasma Concentration (Cmax) in venous blood(Between T0 (inclusion) and T360 (6hours after inclusion))
- Tranexamic acid concentration in uterine bleeding(Between T0 (inclusion) and T360 (6hours after inclusion))
- the number of patients developing an oliguria or a renal failure (RIFLE score more than 2)(Between T0 (inclusion) and T360 (6hours later))
- Visual disturbances(Between T0 (inclusion) and Day 42)
- Lagtime between thrombin and plasmin peaks (s) in venous blood(Between T0 (inclusion) and T360 (6hours after inclusion))
- Area under the plasma concentration versus time curve (AUC) in uterine bleeding(Between T0 (inclusion) and T360 (6hours after inclusion))
- Lagtime between thrombin and plasmin peaks (s) in uterine bleeding(Between T0 (inclusion) and T360 (6hours after inclusion))