TRAnexamic Acid for Preventing Blood Loss Following a Cesarean Delivery in Women With Placenta pREVIA: a Multicenter Randomised, Double Blind Placebo Controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 1,380
- 试验地点
- 1
- 主要终点
- Incidence of red blood cell transfusion (binary outcome) between delivery of child and discharge from postpartum hospital stay.
研究概览
简要总结
Several randomized, controlled trials, mostly involving women undergoing cesarean delivery, have shown that the prophylactic intravenous administration of 1 g of tranexamic acid after childbirth reduced blood loss. Most were small, single-centre trials with considerable methodologic limitations.
It is important to emphasize that none of these RCTs has included women at increased risk of PPH such as placenta previa, a context in which the prevalence of moderate and severe blood loss is significantly higher and where the magnitude of the effect of TXA may highly differ compared to low risk women
详细描述
TXA is a promising candidate drug, inexpensive and easy to administer, that can be easily added to the delivery management of women worldwide. Strong evidence that TXA reduces blood transfusion in elective and emergency surgery, outside obstetrics, has been available for many years, whatever the type of surgery (ie cardiac, orthopaedic, hepatic, urological, and vascular surgery). Tranexamic acid was recently shown to reduce bleeding-related mortality among women with postpartum hemorrhage, especially when the drug was administered shortly after delivery. A meta-analysis of data from individual patients including data from patients with trauma and women with postpartum hemorrhage suggested the importance of early treatment.
Several randomized, controlled trials (RCTs), involving women undergoing cesarean delivery, as well have meta-analyses, have shown that the prophylactic intravenous administration of 1 g of tranexamic acid after childbirth reduced blood loss. Most of them were small, single- center trials with considerable methodologic limitations. Thus, no guidelines advocate the use of tranexamic acid to prevent blood loss after cesarean delivery. Moreover, it is important to emphasize that none of these RCTs has included women at increased risk of PPH such as placenta previa, a context in which the prevalence of moderate and severe blood loss is significantly higher and where the magnitude of the effect of TXA may highly differ compared to low risk women.
The aim of our study is to conduct a large multicentre randomised, double blind placebo controlled trial to adequately assess the impact of TXA for preventing PPH following a cesarean delivery in women with placenta previa.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
Double blinding is performed according to current Good Manufacturing Practices (BPF). The packaging and labelling of the experimental drugs are carried out by the PUI of CHU Angers, in accordance with the regulation of the clinical trials in force. PUI of CHU Angers will produce batches of vials (tranexamic acid or placebo according to randomization) according to the model:
- TXA: 1g - 10ml
- Placebo: NaCl 0.9% - 10mL
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Age≥ 18 years
- •Placenta previa defined by a placental edge below 20mm from internal cervical os diagnosed at the most recent transvaginal ultrasound examination before delivery, as per French guidelines
- •Cesarean delivery before or during labor
- •Gestational age at delivery ≥ 32 weeks + 0
- •Affiliated or beneficiary to a health security system
- •Signed informed consent
排除标准
- •History of venous (deep vein thrombosis and/or pulmonary embolism) or arterial (angina pectoris, myocardial infarction, stroke) thrombotic event
- •History of epilepsy or seizure
- •Chronic or acute cardiovascular disease (including foramen oval, mitral stenosis, aortic stenosis, heart transplant, pulmonary hypertension); chronic or acute renal disease (including chronic or acute kidney failure with glomerular filtration rate <90 mL/min, renal transplantation), chronic active or acute liver disorder with hemorrhagic or thrombotic risk (including cirrhosis, portal hypertension, Budd-Chiari syndrome)
- •Active autoimmune disease with thromboembolic risk (including lupus, antiphospholipid syndrome, Crohn's disease)
- •Sickle cell disease (homozygous)
- •Severe hemostasis disorder prothrombotic (Factor V Leiden mutation - homo or heterozygous; Activated protein C (APC) resistance, Protein C deficiency, Protein S deficiency - aside from pregnancy, Homocysteinemia, , Factor 2 mutation - homo or heterozygous, Deficiency in antithrombin 3), prohemorragic (von Willebrand disease requiring desmopressin treatment during delivery, thrombocytopenia (<30000/mm3), Glanzmann disease, hypofibrinogenemia (<1g/L) -aside from pregnancy)
- •High prenatal suspicion of placenta accreta spectrum disorder according to the obstetrician in charge
- •Placenta praevia diagnosed during delivery
- •Abruptio placentae
- •Significant bleeding (estimated blood loss>500ml) within 12 hours before cesarean delivery
- •Eclampsia / HELLP syndrome
- •In utero fetal death
- •Administration of low-molecular-weight heparin or antiplatelet agents during the 7 days before delivery
- •Tranexamic acid contraindication
- •Sodium chloride contraindication
- •Women under legal protection
- •Poor understanding of the French language
研究组 & 干预措施
Tranexamic acid
After the routine prophylactic IV or IM injection of the uterotonic used in the hospital protocol's -either oxytocin or carbetocin - (as recommended by the 2014 guidelines for prevention and management of postpartum hemorrhage from the CNGOF), the intervention will be the IV administration of a 10-ml blinded ampoule of the study drug (either TXA or placebo according to the randomisation sequence) to the patient within 3 minutes after birth, slowly (over 30-60 seconds), once the cord has been clamped
干预措施: Tranexamic Acid / Sodium chloride (Drug)
Placebo
After the routine prophylactic IV or IM injection of the uterotonic used in the hospital protocol's -either oxytocin or carbetocin - (as recommended by the 2014 guidelines for prevention and management of postpartum hemorrhage from the CNGOF), the intervention will be the IV administration of a 10-ml blinded ampoule of the study drug (either TXA or placebo according to the randomisation sequence) to the patient within 3 minutes after birth, slowly (over 30-60 seconds), once the cord has been clamped
干预措施: Tranexamic Acid / Sodium chloride (Drug)
结局指标
主要结局
Incidence of red blood cell transfusion (binary outcome) between delivery of child and discharge from postpartum hospital stay.
时间窗: baseline
Incidence of red blood cell transfusion (binary outcome) between delivery of child and discharge from postpartum hospital stay.
次要结局
- arterial embolisation(Baseline)
- maternal postpartum transfer(Baseline)
- supplementary uterotonic treatment(Baseline)
- change in peripartum Hb(day 2)
- maternal death for any cause(Baseline)
- Occurrence of calculated blood loss > 1500ml.(Baseline)
- iron sucrose perfusion(Baseline)
- change in peripartum Ht(day 2)
- gravimetrically estimated blood loss(Baseline)
- linically significant PPH(Baseline)
- red blood cell units transfusion(Baseline)
- number of transfusion(Baseline)
- proportion of breastfeeding at hospital discharge(Baseline)
- thromboembolic events(week 12)
- Occurrence of calculated blood loss > 1000ml.(Baseline)
- mean calculated blood loss(Baseline)
- shock index(15, 30, 45, 60 and 120 minutes after birth)
- mild adverse reactions of TXA(Hospitalization stay)
- Women's satisfaction and psychological status(Week 8; Week 12)
- transfer to neonatal ICU(Baseline)