Novel Vacuum-Induced Postpartum Hemorrhage Control: a Multicenter Randomized Trial.

摘要 每年，世界各地有1.3亿名妇女接生，估计有1400万人经历了 产后出血(PPh)−最近重新定义为累计失血量1000ml或以上或失血 与血容量不足的体征或症状有关，与分娩途径无关。PPH是领先的 全世界孕产妇死亡的原因，占产科原因产妇死亡的25%，其中99% 发生在低收入和中低收入国家(LMIC)。产后出血最常见的原因是宫缩乏力 产后子宫不能充分收缩的−占所有−的70%。主动型 第三产程的处理，包括预防性宫缩、控制性脐带 牵引和子宫按摩可将产后出血的发生率降低约66%。当PPH发生时 在这些预防措施中，治疗选择包括额外的子宫强直(医疗)、子宫填塞。 (机械)和外科干预(血管结扎、子宫压缩缝合和子宫切除术)。 当药物治疗不成功时，子宫气囊填塞通常是二线治疗。 通过将充气装置插入子宫以对子宫施加向外压缩来实现的 墙壁。尽管它被广泛使用，但它的机制与生理性子宫收缩背道而驰 在分娩后发生，以控制出血。延长的治疗时间(通常为12-24小时)进一步限制了它的使用 小时)，尿路闭塞，无法显示任何持续出血。最常见的低成本选项− 避孕套导管−用于LMICs，但最近的两项随机试验显示，产妇的情况没有改善 结果和可能的危害。因此，迫切需要有效和安全的治疗选择，以减少 PPH的负担，特别是在低收入国家。 JADA®系统是FDA批准的新型宫内真空诱导出血控制装置，专门用于 专为PPH的快速治疗而设计。它通过应用低水平的宫内阴性来模拟产后生理 加压以利于子宫压迫血管的收缩，达到止血的目的。 来自两项研究的初步数据显示了有希望的结果，但这些数据因缺乏控制而受到限制 群体，可能的选择偏差和适度的样本量，这排除了关于以下方面的明确结论 Jada®系统的相对有效性和安全性。我们提出了第一个确定的随机对照 对JADA®系统在治疗PPH中有效、安全和成本效益的假设进行试验，比较 转到标准护理。一支拥有产科、全球卫生和临床专业知识的多学科研究团队 试验将招募424名妇女参加加纳的两个大容量产科单元，这是一个PPH负担较高的LMIC，以进行评估 有效性(主要目标)，2)安全性(次要目标1)，以及3)成本效益(次要目标2) 与标准护理相比，JADA®系统在治疗PPH方面具有更大的优势。

ABSTRACT Every year, 130 million women deliver babies around the world, and an estimated 14 million experience postpartum hemorrhage (PPH) − recently redefined as a cumulative blood loss of 1000 ml or more or blood loss associated with signs or symptoms of hypovolemia, irrespective of the route of delivery. PPH is the leading cause of maternal mortality worldwide, responsible for 25% of maternal deaths from obstetric causes, with 99% occurring in low and lower-middle income countries (LMICs). The most common cause of PPH is uterine atony − when the uterus fails to adequately contract after childbirth − accounting for 70% of all PPH. Active management of the third stage of labor, consisting of administering prophylactic uterotonics, controlled cord traction, and uterine massage, reduces the incidence of PPH by approximately 66%. When PPH occurs in spite of these preventive measures, therapeutic options include additional uterotonics (medical), uterine tamponade (mechanical) and surgical interventions (vascular ligation, uterine compression sutures and hysterectomy). Uterine balloon tamponade is often the second line therapy when medical management is unsuccessful and is achieved with inflatable devices inserted into the uterus to exert outward compression on the uterine walls. Despite its widespread use, its mechanism is counterintuitive to the physiologic uterine contraction that occurs after delivery to control bleeding. Its use is further limited by prolonged treatment times (typically 12-24 hours), urinary tract occlusion, and inability to reveal any continuing bleeding. Low-cost options − most commonly condom catheters − are used in LMICs, but two recent randomized trials showed no improvement in maternal outcomes and possible harm. Thus, there is an urgent need for effective and safe treatment options to reduce the burden of PPH particularly in LMICs. The Jada® System is a novel FDA-cleared intrauterine vacuum-induced hemorrhage-control device specifically designed for rapid treatment of PPH. It mimics postpartum physiology by applying low-level intrauterine negative pressure to facilitate uterine compressive forces for constriction of blood vessels to achieve hemostasis. Preliminary data from two studies have shown promising results, but these data are limited by lack of control groups, possible selection bias and the modest sample sizes which preclude definitive conclusions regarding the relative effectiveness and safety of the Jada® System. We propose the first definitive, randomized control trial to test the hypothesis that the Jada® System is effective, safe and cost-effective in treating PPH, compared to standard care. A multidisciplinary team of investigators with expertise in obstetrics, global health and clinical trials will enroll 424 women in two high volume obstetric units in Ghana, a LMIC with high PPH burden, to evaluate the effectiveness (Primary Aim), 2) safety (Secondary Aim 1), and 3) cost-effectiveness (Secondary Aim 2) of the Jada® System, compared to standard care, in treating PPH.