Department of Anesthesia, Sunnybrook Health Sciences Centre, University of Toronto, M3-200, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada.
Department of Anesthesia, North York General Hospital, Toronto, ON, Canada.
Sci Rep. 2023 Mar 18;13(1):4512. doi: 10.1038/s41598-023-30947-8.
Postpartum haemorrhage (PPH) is a leading cause of maternal morbidity and mortality. While tranexamic acid (TXA) reduces bleeding and transfusion requirements in established PPH, we sought to determine the feasibility of conducting a fully powered trial assessing the effect of prophylactic tranexamic acid, prior to PPH onset, in a Canadian Obstetric setting. With institutional and Health Canada approval, consenting, eligible parturients (singleton, > 32 weeks gestation, vaginal or caesarian delivery) were randomly assigned to receive TXA (1 g intravenously) or placebo (0.9% saline) prior to delivery. Participants, investigators, data collectors/adjudicators, and analysis was blinded. The primary outcome was administration of study intervention to > 85% of randomized individuals. Secondary outcomes included recruitment rate (feasibility) and safety outcomes. Over 8 months, 611 were approached, 35 consented, and 27 randomized (14 TXA, 13 placebo). 89% of randomized participants received the assigned intervention. Recruitment fell below feasibility (23% target). No serious adverse outcomes occurred. Our pilot trial in a Canadian Obstetric setting was unable to demonstrate feasibility to conduct a large, multicentre trial to examine prophylactic use of tranexamic for PPH secondary to the complex regulatory requirements associated with a trial for an off-label, but commonly utilized intervention. These challenges should inform stakeholders on the resources and challenges of conducting future trials using off-label interventions.Trial registration: www.clinicaltrials.gov , NCT03069859 (03/03/2017).
产后出血（PPH）是产妇发病率和死亡率的主要原因。虽然氨甲环酸（TXA）可减少已确立的 PPH 的出血和输血需求，但我们试图确定在加拿大产科环境中进行评估预防性氨甲环酸（在 PPH 发作之前）效果的完全有能力试验的可行性。在获得机构和加拿大卫生部批准、同意的情况下，合格的产妇（单胎、>32 周妊娠、阴道或剖宫产分娩）在分娩前被随机分配接受 TXA（1g 静脉内）或安慰剂（0.9%生理盐水）。参与者、研究者、数据收集者/裁决者和分析均为盲法。主要结局是>85%随机个体接受研究干预。次要结局包括招募率（可行性）和安全性结局。在 8 个月期间，共 611 人被接触，35 人同意，27 人被随机分配（14 人接受 TXA，13 人接受安慰剂）。89%的随机参与者接受了指定的干预措施。招募率低于可行性（目标 23%）。没有发生严重不良结局。我们在加拿大产科环境中的试点试验未能证明进行大型多中心试验以检验预防性使用氨甲环酸预防因标签外但常用的干预措施而导致的 PPH 的可行性。这些挑战应告知利益相关者有关使用标签外干预措施进行未来试验的资源和挑战。试验注册：www.clinicaltrials.gov，NCT03069859（2017 年 3 月 3 日）。
