Clinical Trials Unit, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK.
Holy Family Hospital, Gynaecology & Obstetrics Unit 1, F-762 Said Pur Road, Satellite Town, Rawalpindi, Pakistan.
BMC Pregnancy Childbirth. 2018 Jun 7;18(1):215. doi: 10.1186/s12884-018-1855-5.
In severe post-partum haemorrhage, death can occur within hours of bleeding onset so interventions to control the bleeding must be given immediately. In clinical trials of treatments for life-threatening bleeding, established treatments are given priority and the trial treatment is usually given last. However, enrolling patients in whom severe maternal morbidity or death is imminent or inevitable at the time of randomisation may dilute the effects of a trial treatment.
We conducted an exploratory analysis of data from the WOMAN trial, an international, randomised placebo-controlled trial of the effects of tranexamic acid on death and surgical intervention in 20,060 women with post-partum haemorrhage. We assessed the impact of early maternal death or hysterectomy due to exsanguination on the effect of tranexamic acid on each of these respective outcomes. We conducted repeated analyses excluding patients with these outcomes at increasing intervals from the time of randomisation. We quantified treatment effects using risk ratios (RR) and 99% confidence intervals (CI) and prepared cumulative failure plots.
Among 14,923 women randomised within 3 h of delivery (7518 tranexamic acid and 7405 placebo), there were 216 bleeding deaths (1.5%) and 383 hysterectomies due to bleeding (2.8%). After excluding deaths from exsanguination at increasing time intervals following randomization, there was a significant reduction in the risk of death due to bleeding with tranexamic acid (RR = 0.41; 99% CI 0.19-0.89). However, after excluding hysterectomies at increasing time intervals post-randomization, there was no reduction in the risk of hysterectomy due to bleeding with tranexamic acid (RR = 0.79; 99% CI 0.33-1.86).
Findings from this analysis provide further evidence that tranexamic acid reduces the risk of death from exsanguination in women who experience postpartum haemorrhage. It is uncertain whether tranexamic acid reduces the risk of hysterectomy for bleeding after excluding early hysterectomies.
ISRCTN trial registration number ISRCTN76912190, 8 Dec 2008; ClinicalTrials.gov number NCT00872469, 30 March 2009; PACTR number PACTR201007000192283, 9 Feb 2010; EudraCT number 2008-008441-38, 8 Dec 2010 (retrospectively registered).
在严重的产后出血中，出血发生后数小时内可能导致死亡，因此必须立即采取措施控制出血。在危及生命的出血治疗的临床试验中，已确立的治疗方法被优先考虑，而试验治疗通常放在最后。然而，在随机分组时，患者已经出现严重的产妇发病率或死亡的可能性或必然性，可能会削弱试验治疗的效果。
我们对 WOMAN 试验的数据进行了探索性分析，该试验是一项国际性、随机、安慰剂对照试验，评估了氨甲环酸对 20060 名产后出血妇女死亡和手术干预的影响。我们评估了早期产妇死亡或因出血性休克而进行子宫切除术对氨甲环酸对这两种结局的影响。我们通过排除随机分组后不同时间间隔出现这些结局的患者进行了重复分析。我们使用风险比（RR）和 99%置信区间（CI）来量化治疗效果，并绘制累积失败图。
在分娩后 3 小时内随机分配的 14923 名妇女中，有 216 例出血性死亡（1.5%）和 383 例因出血性原因进行的子宫切除术（2.8%）。排除随机分组后不同时间间隔因出血性休克导致的死亡后，氨甲环酸降低了出血性死亡的风险（RR=0.41；99%CI 0.19-0.89）。然而，排除随机分组后不同时间间隔因出血性原因进行的子宫切除术后，氨甲环酸并没有降低因出血性原因进行子宫切除术的风险（RR=0.79；99%CI 0.33-1.86）。
这项分析的结果进一步提供了证据表明，氨甲环酸可降低产后出血妇女因出血性休克导致的死亡风险。在排除早期子宫切除术后，尚不确定氨甲环酸是否降低了因出血性原因进行子宫切除术的风险。
ISRCTN 试验注册编号 ISRCTN88702190，2008 年 12 月 8 日；ClinicalTrials.gov 注册号 NCT00872469，2009 年 3 月 30 日；PACT 注册号 PACTR201007000192283，2010 年 2 月 9 日；EudraCT 编号 2008-008441-38，2010 年 12 月 8 日（追溯注册）。
