WOMAN-PharmacoTXA trial: Study protocol for a randomised controlled trial to assess the pharmacokinetics and pharmacodynamics of intramuscular, intravenous and oral administration of tranexamic acid in women giving birth by caesarean section.
WOMAN-PharmacoTXA trial: Study protocol for a randomised controlled trial to assess the pharmacokinetics and pharmacodynamics of intramuscular, intravenous and oral administration of tranexamic acid in women giving birth by caesarean section.
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DOI：
10.12688/wellcomeopenres.16884.1
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发表时间：
2021
影响因子：
--
通讯作者：
Shakur-Still H
中科院分区：
文献类型：
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作者：
Arribas M;Roberts I;Chaudhri R;Geer A;Prowse D;Lubeya MK;Kayani A;Javaid K;Grassin-Delyle S;Shakur-Still H
背景：产后出血 (PPH) 妇女在出生 3 小时内静脉注射氨甲环酸 (TXA) 可显着减少因出血导致的死亡。大多数 PPH 死亡发生在分娩后的头几个小时内，治疗延迟会降低生存率。 快速 TXA 治疗的一大障碍是需要静脉注射。 TXA 的肌肉注射和口服溶液的给药将更容易、更快捷，并且需要更少的培训。然而，TXA在孕妇中不同途径给药的药代动力学（PK）、药效学和安全性尚未确定。本研究的主要目的是确定肌肉注射和 TXA 口服溶液的吸收水平是否足以抑制孕妇的纤维蛋白溶解。 方法：WOMAN-PharmacoTXA 是一项前瞻性、随机、开放标签试验，将在赞比亚和巴基斯坦进行。 至少有一种 PPH 危险因素且接受剖腹产的成年女性将被包括在内。 妇女将在剖腹产前约 1 小时随机接受以下药物之一：1 克 TXA IV、1 克 TXA IM、4 克 TXA 口服溶液或无 TXA。随机化将持续进行，直至纳入至少 6 个随机化后 PK 样本的 120 名参与者。将在基线和接受干预后 24 小时内的不同时间点测量母体血液样本中的 TXA 浓度。将从脐带和新生儿处测量血液 TXA 浓度。 主要终点是随着时间的推移母体血液 TXA 浓度。次要结局包括脐带和新生儿 TXA 浓度、D-二聚体浓度、失血量和 PPH 的临床诊断、注射部位反应以及母体和新生儿不良事件。 讨论：WOMAN-PharmacoTXA 试验将为剖腹产妇女静脉注射、肌肉注射和口服 TXA 后的药代动力学、药效学和安全性提供重要数据。 试验注册：ClincalTrials.gov，NCT04274335（18/02/2020）。
Background: Intravenous tranexamic acid (TXA) within 3 hours of birth significantly reduces death due to bleeding in women with postpartum haemorrhage (PPH). Most PPH deaths occur in the first hours after giving birth and treatment delay decreases survival. One barrier to rapid TXA treatment is the need for intravenous injection. Intramuscular injection and oral solution of TXA would be easier and faster to administer and would require less training. However, the pharmacokinetics (PK), pharmacodynamics and safety of TXA administered by different routes in pregnant women have not been established. The main aim of this study is to ascertain whether IM and oral solution of TXA will be absorbed at levels sufficient to inhibit fibrinolysis in pregnant women. Methods: WOMAN-PharmacoTXA is a prospective, randomised, open label trial to be conducted in Zambia and Pakistan. Adult women undergoing caesarean section with at least one risk factor for PPH will be included. Women will be randomised to receive one of the following about 1 hour prior to caesarean section: 1-gram TXA IV, 1-gram TXA IM, 4-grams TXA oral solution or no TXA. Randomisation will continue until 120 participants with at least six post randomisation PK samples are included. TXA concentration in maternal blood samples will be measured at baseline and at different time points during 24 hours after receipt of intervention. Blood TXA concentration will be measured from the umbilical cord and neonate. The primary endpoint is maternal blood TXA concentrations over time. Secondary outcomes include umbilical cord and neonate TXA concentration D-dimer concentration, blood loss and clinical diagnosis of PPH, injection site reactions and maternal and neonate adverse events. Discussion: The WOMAN-PharmacoTXA trial will provide important data on pharmacokinetics, pharmacodynamics and safety of TXA after IV, intramuscular and oral administration in women giving birth by caesarean section. Trial registration: ClincalTrials.gov, NCT04274335 (18/02/2020).