Early Factor XIII Replacement in Postpartum Hemorrhage: Multi-center, Randomized, Controlled, Investigator-initiated Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 988
- 试验地点
- 9
- 主要终点
- Blood Loss during post partum hemorrhage
研究概览
简要总结
The goal of this trial is to determine if postpartum blood loss can be reduced by replenishing coagulation factor XIII (FXIII) at an early stage of postpartum hemorrhage (PPH).
Summary of current body of evidence:
- Morbidity and mortality due to PPH is rising.
- Current guidelines focus on replenishment of fibrinogen as an initial step in the treatment of PPH-related coagulopathy, despite non-conclusive evidence in all prospective trials.
- Trials from other specialties demonstrate a significant impact of FXIII on perioperative bleeding complications; a previous study at the University Hospital Zurich showed that pre-partum factor XIII activity had a strong association to postpartum blood loss.
Therefore, this nationwide, multi-center, randomized, controlled trial in multiple perinatal centers across Switzerland will be conducted. The goal is to determine if postpartum blood loss and PPH-related complications can be reduced by replenishing FXIII.
All participating women receive, according to the national guideline, 1g tranexamic acid (TXA) i.v. in case of PPH (measured blood loss [MBL] ≥ 500 mL) during the pre-study phase. Randomization takes place if bleeding continues and exceeds 700mL. The intervention group then receives FXIII (Fibrogammin®) according to approved dosage in addition to obstetric standard of care treatment for causes of PPH; the control group receives only standard of care treatment.
详细描述
Postpartum hemorrhage (PPH) is a main reason for maternal mortality and morbidity. PPH, defined by the WHO as blood loss of 500 mL or more within 24 hours after delivery, causes about 30% of maternal deaths worldwide. The internationally observed trend towards increased PPH-related morbidity and mortality is disturbing and demands new strategies in the prevention and treatment of PPH.
Although the most frequent causes for severe PPH are believed to be uterine atony or retained placenta, virtually all cases of severe PPH lead to a disorder of the coagulation system which itself aggravates bleeding.
At the moment, most guidelines on coagulation management during PPH and expert opinions focus on the replenishment of coagulation factor I (fibrinogen) although three out of three randomized controlled trials with early or pre-emptive administration of fibrinogen during PPH were negative.
Based on earlier research, it was hypothesized that coagulation factor XIII (FXIII) might play a significant role in women with increased postpartum blood loss, because of its role in the establishment of blood clot stability and fibrinolytic resistance. This hypothesis was tested in a prospective diagnostic study involving 1300 parturient women at the University Hospital Zurich and showed that pre-partum factor XIII activity had a strong association to postpartum blood loss.
Therefore, this nationwide, multi-center, open-label, randomized controlled trial in major perinatal centers across Switzerland will be conducted. The goal is to determine if postpartum blood loss and PPH-related complications can be reduced by substitution of FXIII at an early stage of PPH.
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
- Single (Outcomes Assessor)
盲法说明
The analysis of the primary outcome will be performed using blinded treatment arms.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •planned vaginal delivery
- •singleton vital pregnancy
- •gestational age at delivery >= 30+0 weeks
- •maternal weight at admission for delivery <100 kg
排除标准
- •Antithrombotic therapy in pregnancy (therapeutic dosage) until admission for delivery (LMWH, UFH)
- •diagnosis of preeclampsia (ISSHP classification , eclampsia or HELLP syndrome),
- •known history of deep vein thrombosis or pulmonary embolism,
- •known diagnosis of bleeding disorder or thrombophilia,
- •known thrombocytopenia during second half of pregnancy with thrombocytes < 100 G/L,
- •known anemia during second half of pregnancy with Hb<80 g/L,
- •known sickle cell disease,
- •known malignant tumor(s),
- •participation in another study with investigational drug within the 30 days preceding and during the present study,
- •inability to follow the procedures of the study, e.g. due to language problems,
- •known or suspected non-compliance, drug or alcohol abuse.
- •Exclusion criteria prior randomization
- •Maternal fever ≥39.0°C
- •unplanned cesarean delivery is performed,
- •Measured Blood Loss remains < 700 mL after administration of 1g tranexamic acid .
- •Postpartum hemorrhage due to occult bleeding (intra-abdominal, retroperitoneal, parametric),
研究组 & 干预措施
Fibrogammin (FXIII)
Women in the intervention group receive FXIII intravenously in addition to the standard of care treatment for PPH. FXIII is administered when blood loss is > 700 ml. Women weighing <80 kg receive 1250 IU Fibrogammin®; women weighing 80-99.9 kg receive 1500 IU Fibrogammin®; thus ensuring a dose of 15-20 IU FXIII per kg body weight according to the manufacturer's recommendation.
干预措施: Fibrogammin (Drug)
结局指标
主要结局
Blood Loss during post partum hemorrhage
时间窗: Day 1 (within 24 hours after delivery)
Measured blood loss, in ml
次要结局
- Outcome of postpartum hemorrhage(Time point of assessment will be 48 hours (range 36 to 60) postpartum, if not stated otherwise)
- Changes in hematological standard value: hemoglobin(shortly before delivery and 48 hours (range 36 to 60 hours) after delivery)
- Changes in hematological standard value: leucocyte count(shortly before delivery and 48 hours (range 36 to 60 hours) after delivery)
- Changes in hematological standard value; thrombocyte count(shortly before delivery and 48 hours (range 36 to 60 hours) after delivery)
- Hospital costs(from admission to hospital until hospital discharge, up to 9 weeks)
- Breastfeeding(6 - 9 weeks after delivery)
- Patient survey (in a subgroup of patients only)(discharge from hospital, estimated 3 - 5 days after delivery)