Hermans Frederik J R, Schuit Ewoud, Opmeer Brent C, Oudijk Martijn A, Bekker Mireille, Woiski Mallory, Bax Caroline J, Sueters Marieke, Scheepers Hubertina C J, Franssen Maureen T M, Pajkrt Eva, Mol Ben Willem J, Kok Marjolein
Department of Obstetrics and Gynaecology, Academic Medical Center, Amsterdam, The Netherlands.
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands.
BMC Pregnancy Childbirth. 2016 Jul 12;16(1):154. doi: 10.1186/s12884-016-0935-7.
Preterm birth is a major cause of neonatal mortality and morbidity. As preventive strategies are largely ineffective, threatened preterm labor is a frequent problem that affects approximately 10 % of pregnancies. In recent years, risk assessment in these women has incorporated cervical length measurement and fetal fibronectin testing, and this has improved the capacity to identify women at increased risk for delivery within 14 days. Despite these improvements, risk for preterm birth continues to be increased in women who did not deliver after an episode of threatened preterm labor, as indicated by a preterm birth rate between 30 to 60 % in this group of women. Currently no effective treatment is available. Studies on maintenance tocolysis and progesterone have shown ambiguous results. The pessary has not been evaluated in women with threatened preterm labor, however studies in asymptomatic women with a short cervix show reduced rates of preterm birth rates as well as perinatal complications. The APOSTEL VI trial aims to assess the effectiveness of a cervical pessary in women who did not deliver within 48 h after an episode of threatened preterm labor.
METHODS/DESIGN: This is a nationwide multicenter open-label randomized clinical trial. Women with a singleton or twin gestation with intact membranes, who were admitted for threatened preterm labor, at a gestational age between 24 and 34 weeks, a cervical length between 15 and 30 mm and a positive fibronectin test or a cervical length below 15 mm, who did not deliver after 48 h will be eligible for inclusion. Women will be allocated to a pessary or no intervention (usual care). Primary outcome is preterm delivery < 37 weeks. Secondary outcomes are amongst others a composite of perinatal morbidity and mortality. Sample size is based on an expected 50 % reduction of preterm birth before 37 weeks (two-sided test, α 0.05 and β 0.2). Two hundred women with a singleton pregnancy need to be randomized. Analysis will be done by intention to treat.
The APOSTEL VI trial will provide evidence whether a pessary is effective in preventing preterm birth in women who did not deliver 48 h after admission for threatened preterm labor and who remain at high risk for preterm birth.
Trial is registered at the Dutch Trial Register: http://www.trialregister.nl , NTR4210, date of registration: October 16th 2013.
早产是新生儿死亡和发病的主要原因。由于预防策略大多无效，先兆早产是一个常见问题，约影响10%的妊娠。近年来，对这些女性的风险评估纳入了宫颈长度测量和胎儿纤维连接蛋白检测，这提高了识别14天内分娩风险增加女性的能力。尽管有这些改进，但经历过先兆早产发作后未分娩的女性早产风险仍然增加，该组女性的早产率在30%至60%之间。目前尚无有效的治疗方法。关于维持性宫缩抑制和孕酮的研究结果尚不明确。子宫托尚未在先兆早产女性中进行评估，然而，对无症状宫颈短的女性的研究显示早产率以及围产期并发症发生率降低。APOSTEL VI试验旨在评估子宫托对先兆早产发作后48小时内未分娩女性的有效性。
方法/设计：这是一项全国性多中心开放标签随机临床试验。单胎或双胎妊娠、胎膜完整、因先兆早产入院、孕周在24至34周之间、宫颈长度在15至30毫米之间且胎儿纤维连接蛋白检测呈阳性或宫颈长度低于15毫米、48小时后未分娩的女性将符合纳入标准。女性将被分配接受子宫托治疗或不干预（常规护理）。主要结局是孕周<37周的早产。次要结局包括围产期发病率和死亡率的综合情况。样本量基于预期37周前早产率降低50%（双侧检验，α 0.05，β 0.2）。需要对200名单胎妊娠女性进行随机分组。分析将按意向性分析进行。
APOSTEL VI试验将提供证据，证明子宫托对先兆早产入院后48小时内未分娩且仍有早产高风险的女性预防早产是否有效。
该试验已在荷兰试验注册中心注册：http://www.trialregister.nl ，NTR4210，注册日期：2013年10月16日。
