Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
Institute of Applied Health Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
Health Technol Assess. 2020 Jun;24(33):1-70. doi: 10.3310/hta24330.
Progesterone is essential for a healthy pregnancy. Several small trials have suggested that progesterone therapy may rescue a pregnancy in women with early pregnancy bleeding, which is a symptom that is strongly associated with miscarriage.
(1) To assess the effects of vaginal micronised progesterone in women with vaginal bleeding in the first 12 weeks of pregnancy. (2) To evaluate the cost-effectiveness of progesterone in women with early pregnancy bleeding.
A multicentre, double-blind, placebo-controlled, randomised trial of progesterone in women with early pregnancy vaginal bleeding.
A total of 48 hospitals in the UK.
Women aged 16-39 years with early pregnancy bleeding.
Women aged 16-39 years were randomly assigned to receive twice-daily vaginal suppositories containing either 400 mg of progesterone or a matched placebo from presentation to 16 weeks of gestation.
The primary outcome was live birth at ≥ 34 weeks. In addition, a within-trial cost-effectiveness analysis was conducted from an NHS and NHS/Personal Social Services perspective.
A total of 4153 women from 48 hospitals in the UK received either progesterone ( = 2079) or placebo ( = 2074). The follow-up rate for the primary outcome was 97.2% (4038 out of 4153 participants). The live birth rate was 75% (1513 out of 2025 participants) in the progesterone group and 72% (1459 out of 2013 participants) in the placebo group (relative rate 1.03, 95% confidence interval 1.00 to 1.07; = 0.08). A significant subgroup effect (interaction test = 0.007) was identified for prespecified subgroups by the number of previous miscarriages: none (74% in the progesterone group vs. 75% in the placebo group; relative rate 0.99, 95% confidence interval 0.95 to 1.04; = 0.72); one or two (76% in the progesterone group vs. 72% in the placebo group; relative rate 1.05, 95% confidence interval 1.00 to 1.12; = 0.07); and three or more (72% in the progesterone group vs. 57% in the placebo group; relative rate 1.28, 95% confidence interval 1.08 to 1.51; = 0.004). A significant post hoc subgroup effect (interaction test = 0.01) was identified in the subgroup of participants with early pregnancy bleeding and any number of previous miscarriage(s) (75% in the progesterone group vs. 70% in the placebo group; relative rate 1.09, 95% confidence interval 1.03 to 1.15; = 0.003). There were no significant differences in the rate of adverse events between the groups. The results of the health economics analysis show that progesterone was more costly than placebo (£7655 vs. £7572), with a mean cost difference of £83 (adjusted mean difference £76, 95% confidence interval -£559 to £711) between the two arms. Thus, the incremental cost-effectiveness ratio of progesterone compared with placebo was estimated as £3305 per additional live birth at ≥ 34 weeks of gestation.
Progesterone therapy in the first trimester of pregnancy did not result in a significantly higher rate of live births among women with threatened miscarriage overall, but an important subgroup effect was identified. A conclusion on the cost-effectiveness of the PRISM trial would depend on the amount that society is willing to pay to increase the chances of an additional live birth at ≥ 34 weeks. For future work, we plan to conduct an individual participant data meta-analysis using all existing data sets.
Current Controlled Trials ISRCTN14163439, EudraCT 2014-002348-42 and Integrated Research Application System (IRAS) 158326.
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 24, No. 33. See the NIHR Journals Library website for further project information.
孕激素对于健康妊娠至关重要。一些小型试验表明，孕激素疗法可能挽救有早孕出血症状的妊娠，该症状与流产密切相关。
（1）评估阴道用微粒化黄体酮治疗妊娠 12 周内阴道出血的女性的效果。（2）评估在有早孕出血的女性中使用孕激素的成本效益。
一项在英国 48 家医院开展的多中心、双盲、安慰剂对照、随机孕激素治疗早孕阴道出血的试验。
英国共 48 家医院。
年龄 16-39 岁的早孕阴道出血的女性。
年龄 16-39 岁的女性随机分配接受每日两次阴道栓剂治疗，分别给予 400mg 黄体酮或匹配安慰剂，从就诊至妊娠 16 周。
主要结局是≥34 周的活产率。此外，还从英国国家医疗服务体系（NHS）和 NHS/个人社会服务的角度进行了一次试验内成本效益分析。
英国 48 家医院的 4153 名女性接受了孕激素（n=2079）或安慰剂（n=2074）治疗。主要结局的随访率为 97.2%（4038 名参与者中的 4038 名）。孕激素组的活产率为 75%（2025 名参与者中的 1513 名），安慰剂组为 72%（2013 名参与者中的 1459 名）（相对风险 1.03，95%置信区间 1.00 至 1.07； = 0.08）。对于预先指定的亚组，根据既往流产次数，确定了显著的亚组效应（交互检验 = 0.007）：无（孕激素组 74%，安慰剂组 75%；相对风险 0.99，95%置信区间 0.95 至 1.04； = 0.72）；一至两次（孕激素组 76%，安慰剂组 72%；相对风险 1.05，95%置信区间 1.00 至 1.12； = 0.07）；三次或更多次（孕激素组 72%，安慰剂组 57%；相对风险 1.28，95%置信区间 1.08 至 1.51； = 0.004）。对于有早孕出血和任意次数既往流产的参与者亚组，确定了一个显著的事后亚组效应（交互检验 = 0.01）：孕激素组 75%，安慰剂组 70%；相对风险 1.09，95%置信区间 1.03 至 1.15； = 0.003）。两组间不良事件发生率无显著差异。卫生经济学分析结果显示，孕激素组比安慰剂组成本更高（£7655 比 £7572），两组间的平均成本差异为 £83（调整后的平均差异 £76，95%置信区间 -£559 至 £711）。因此，与安慰剂相比，孕激素的增量成本效益比估计为每增加一个≥34 周的活产率 £3305。
在妊娠早期使用孕激素治疗有先兆流产的女性，总体上并未导致活产率显著提高，但确定了一个重要的亚组效应。PRISM 试验的成本效益结论将取决于社会愿意支付多少来增加≥34 周的活产率。对于未来的工作，我们计划使用所有现有的数据集进行个体参与者数据的荟萃分析。
当前对照试验 ISRCTN81622357、EudraCT 2014-002348-42 和综合研究应用系统（IRAS）158326。
本项目由英国国家卫生研究院（NIHR）卫生技术评估计划资助，将在 中全文发表；第 24 卷，第 33 期。有关该项目的更多信息，请访问 NIHR 期刊库网站。
