Clinical and Population Perinatal Health Research, Kolling Institute of Medical Research, Department of Obstetrics and Gynaecology, University of Sydney, and Royal North Shore Hospital, NSW Australia.
BMC Pregnancy Childbirth. 2011 Mar 11;11:19. doi: 10.1186/1471-2393-11-19.
Prevention of preterm birth remains one of the most important challenges in maternity care. We propose a randomised trial with: a simple Candida testing protocol that can be easily incorporated into usual antenatal care; a simple, well accepted, treatment intervention; and assessment of outcomes from validated, routinely-collected, computerised databases.
METHODS/DESIGN: Using a prospective, randomised, open-label, blinded-endpoint (PROBE) study design, we aim to evaluate whether treating women with asymptomatic vaginal candidiasis early in pregnancy is effective in preventing spontaneous preterm birth. Pregnant women presenting for antenatal care<20 weeks gestation with singleton pregnancies are eligible for inclusion. The intervention is a 6-day course of clotrimazole vaginal pessaries (100 mg) and the primary outcome is spontaneous preterm birth<37 weeks gestation.The study protocol draws on the usual antenatal care schedule, has been pilot-tested and the intervention involves only a minor modification of current practice. Women who agree to participate will self-collect a vaginal swab and those who are culture positive for Candida will be randomised (central, telephone) to open-label treatment or usual care (screening result is not revealed, no treatment, routine antenatal care). Outcomes will be obtained from population databases.A sample size of 3,208 women with Candida colonisation (1,604 per arm) is required to detect a 40% reduction in the spontaneous preterm birth rate among women with asymptomatic candidiasis from 5.0% in the control group to 3.0% in women treated with clotrimazole (significance 0.05, power 0.8). Analyses will be by intention to treat.
For our hypothesis, a placebo-controlled trial had major disadvantages: a placebo arm would not represent current clinical practice; knowledge of vaginal colonisation with Candida may change participants' behaviour; and a placebo with an alcohol preservative may have an independent affect on vaginal flora. These disadvantages can be overcome by the PROBE study design.This trial will provide definitive evidence on whether screening for and treating asymptomatic candidiasis in pregnancy significantly reduces the rate of spontaneous preterm birth. If it can be demonstrated that treating asymptomatic candidiasis reduces preterm births this will change current practice and would directly impact the management of every pregnant woman.
Australian New Zealand Clinical Trials Registry ACTRN12610000607077.
预防早产仍然是产科护理中最具挑战性的问题之一。我们提出了一项随机试验，具有以下特点：简单的念珠菌检测方案，可轻松纳入常规产前护理；简单、易于接受的治疗干预措施；以及使用经过验证的、常规收集的计算机化数据库评估结局。
方法/设计：本研究采用前瞻性、随机、开放标签、盲终点（PROBE）研究设计，旨在评估在妊娠早期无症状性阴道念珠菌病的女性中，早期治疗是否有效预防自发性早产。有单胎妊娠且妊娠 20 周前就诊的孕妇符合纳入条件。干预措施为 6 天克霉唑阴道栓剂（100mg）疗程，主要结局为自发性早产<37 周。该研究方案借鉴了常规产前护理计划，已进行了试点测试，干预措施仅涉及对当前实践的微小修改。同意参与的女性将自行采集阴道拭子，培养阳性的念珠菌女性将随机（中央、电话）分配至开放标签治疗或常规护理（不揭示筛查结果、不治疗、常规产前护理）。结局将从人群数据库中获得。需要 3208 例有念珠菌定植的女性（每组 1604 例）入组，才能检测到无症状念珠菌病女性自发性早产率从对照组的 5.0%降至克霉唑治疗组的 3.0%（对照组和治疗组分别为 5.0%和 3.0%），有统计学意义（显著性水平 0.05，效能 0.8）。分析将采用意向治疗。
对于我们的假设，安慰剂对照试验有很大的缺点：安慰剂组不代表当前的临床实践；阴道念珠菌定植的知识可能会改变参与者的行为；含有酒精防腐剂的安慰剂可能对阴道菌群有独立的影响。PROBE 研究设计可以克服这些缺点。本试验将提供确凿的证据，证明妊娠期间筛查和治疗无症状性念珠菌病是否显著降低自发性早产率。如果能够证明治疗无症状性念珠菌病可以减少早产，这将改变当前的实践，并直接影响每一位孕妇的管理。
澳大利亚和新西兰临床试验注册 ACTRN12610000607077。
