Suppr超能文献

产后出血伴贫血妇女:临床试验结局指标评估。

Postpartum haemorrhage in anaemic women: assessing outcome measures for clinical trials.

机构信息

London School of Hygiene and Tropical Medicine, Clinical Trials Unit, Keppel Street, London, WC1E 7HT, UK.

Department of Obstetrics and Gynaecology, University College Hospital, Ibadan, Oyo State, Nigeria.

出版信息

Trials. 2022 Mar 18;23(1):220. doi: 10.1186/s13063-022-06140-z.

Abstract

BACKGROUND

Postpartum haemorrhage (PPH) is a leading cause of maternal mortality worldwide. Maternal anaemia greatly increases the risk of PPH, and over a third of all pregnant women are anaemic. Because anaemia reduces the oxygen-carrying capacity of the blood, anaemic women cannot tolerate the same volume of blood loss as healthy women. Yet the same blood loss threshold is used to define PPH in all women. The lack of an established PPH definition in anaemic women means the most appropriate outcome measures for use in clinical trials are open to question. We used data from the WOMAN-2 trial to examine different definitions of PPH in anaemic women and consider their appropriateness as clinical trial outcome measures.

MAIN BODY

The WOMAN-2 trial is assessing tranexamic acid (TXA) for PPH prevention in women with moderate or severe anaemia at baseline. To obtain an accurate, precise estimate of the treatment effect, outcome measures should be highly specific and reasonably sensitive. Some outcome misclassification is inevitable. Low sensitivity reduces precision, but low specificity biases the effect estimate towards the null. Outcomes should also be related to how patients feel, function, or survive. The primary outcome in the WOMAN-2 trial, a 'clinical diagnosis of PPH', is defined as estimated blood loss > 500 ml or any blood loss within 24 h sufficient to compromise haemodynamic stability. To explore the utility of several PPH outcome measures, we analysed blinded data from 4521 participants. For each outcome, we assessed its: (1) frequency, (2) specificity for significant bleeding defined as shock index ≥1.0 and (3) association with fatigue (modified fatigue symptom inventory [MFSI]), physical endurance (six-minute walk test) and breathlessness. A clinical diagnosis of PPH was sufficiently frequent (7%), highly specific for clinical signs of early shock (95% specificity for shock index ≥1) and associated with worse maternal functioning after childbirth.

CONCLUSION

Outcome measures in clinical trials of interventions for PPH prevention should facilitate valid and precise estimation of the treatment effect and be important to women. A clinical diagnosis of PPH appears to meet these criteria, making it an appropriate primary outcome for the WOMAN-2 trial.

TRIAL REGISTRATION

ClinicalTrials.gov NCT03475342, registered on 23 March 2018; ISRCTN62396133, registered on 7 December 2017; Pan African Clinical Trial Registry PACTR201909735842379, registered on 18 September 2019.

摘要

背景

产后出血(PPH)是全球孕产妇死亡的主要原因。孕产妇贫血大大增加了 PPH 的风险,超过三分之一的孕妇贫血。由于贫血会降低血液的携氧能力,贫血妇女不能耐受与健康妇女相同的失血量。然而,所有妇女的 PPH 定义都使用相同的失血阈值。在贫血妇女中缺乏既定的 PPH 定义意味着最适合用于临床试验的最佳结局指标仍存在疑问。我们使用 WOMAN-2 试验的数据来检查贫血妇女中不同的 PPH 定义,并考虑它们作为临床试验结局指标的适宜性。

主要内容

WOMAN-2 试验正在评估氨甲环酸(TXA)在基线时患有中度或重度贫血的妇女中的 PPH 预防作用。为了获得治疗效果的准确、精确估计,结局指标应具有高度的特异性和合理的敏感性。一些结局指标的分类错误是不可避免的。低敏感性降低了精确度,但特异性低会使效果估计偏向于零。结局指标还应与患者的感受、功能或生存相关。WOMAN-2 试验的主要结局指标是“临床诊断的 PPH”,定义为估计出血量>500ml 或 24 小时内任何足以导致血流动力学不稳定的失血量。为了探索几种 PPH 结局指标的应用,我们分析了 4521 名参与者的盲法数据。对于每个结局指标,我们评估了其:(1)频率;(2)对定义为休克指数≥1.0 的明显出血的特异性;(3)与疲劳(改良疲劳症状量表[MFSI])、体力耐力(六分钟步行试验)和呼吸困难的相关性。临床诊断的 PPH 发生频率足够高(7%),对早期休克的临床征象具有高度特异性(休克指数≥1 的 95%特异性),并与产后产妇功能恶化相关。

结论

PPH 预防干预临床试验的结局指标应有助于有效和精确地估计治疗效果,并对妇女重要。临床诊断的 PPH 似乎符合这些标准,使其成为 WOMAN-2 试验的合适主要结局指标。

试验注册

ClinicalTrials.gov NCT03475342,于 2018 年 3 月 23 日注册;ISRCTN62396133,于 2017 年 12 月 7 日注册;泛非临床试验注册中心 PACTR201909735842379,于 2019 年 9 月 18 日注册。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1667/8932334/89c77dd5b41b/13063_2022_6140_Fig1_HTML.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验