Screen-and-treat Strategy for Vaginal Flora Abnormalities by Molecular Biology in Pregnant Women at High Risk of Preterm Birth: A Multicentre, Randomized Study (AUTOP 2)
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 1,794
- 主要终点
- The rate of preterm birth
研究概览
简要总结
Preterm birth is a major cause of mortality and long-term disability. Bacterial vaginosis (BV) is a frequent form of dysbiosis that is often asymptomatic and increases the risk of preterm birth. BV is usually diagnosed using conventional tools such as the Nugent score. Molecular diagnosis of BV has now been shown to be more reproducible and to provide a more accurate characterization of dysbiosis.
The main objective of this study is to evaluate the effectiveness of a self screen and treat strategy for vaginal flora dysbiosis, based on molecular point of care (POC) multiplex technology before 18 weeks' gestation, in reducing the rate of preterm birth among pregnant women at high risk, compared with usual care.
The hypothesis is that a Screen-and-Treat strategy using molecular biology among women with previous preterm or/and an history of late abortion could be effective in reducing preterm births by 40%.
详细描述
Preterm birth is an important cause of death and disabilities. Bacterial vaginosis (BV) is a common vaginal dysbiosis or abnormal microbiota, with a predominance of anaerobic bacteria with a lack of Lactobacillus with various diagnosis methods. Often asymptomatic, BV increases the risk of preterm birth according to the gestational age at diagnosis. BV is usually diagnosed by conventional diagnosis such as Nugent score. Molecular diagnosis of BV has now been demonstrated to be more reproducible, accurate and to better define dysbiosis.
AUTOP was a large randomized multicentre trial to evaluate a "Screen and Treat" strategy for bacterial vaginosis using molecular diagnosis of self-collected vaginal samples in low-risk pregnant women during early pregnancy, with an evaluation of treatment success, and including vaginal swab controls.
Among 6,671 randomized women, the Intent to treat analysis of the primary clinical outcome showed no evidence of a reduction in the rate of preterm birth with the screen and treat strategy compared with usual care. The rate of preterm birth was 3.9% (events=127) among 3,333 women in the screen and treat strategy group and 4.6% (events=153) among 3,338 in the control group (aOR, 0.82 [95%CI, 0.65 to 1.05]; P=.12). In the subgroup of nulliparous women (n=3,438), Screening and treating strategy was significantly more effective than usual care (aOR 0.61, 95% CI 0.44 to 0.82; Pinteraction=0.001).
AUTOP I has been submit to JAMA at the beginning of 2023. AUTOP was the first randomized study that evaluates the impact of Screen and Treat strategies using molecular biology during pregnancy, except one ongoing study.
The main objective of AUTOP 2 is to evaluate the effectiveness of a self screen and treat strategy for vaginal flora dysbiosis, based on molecular point of care (POC) multiplex technology before 18 weeks' gestation, in reducing the rate of preterm birth among pregnant women at high risk, compared with usual care.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Pregnant woman over 18 years of age;
- •Single intra uterine pregnancy after 8 weeks and before 18 weeks of gestation (i.e. ≥ 8 weeks and ≤ 18 weeks). Woman can present symptomatic vaginal discharge, or can be asymptomatic or symptomatic with regard to the diagnosis of bacterial vaginosis (BV) with usual technics;
- •With a history of :
- •preterm birth before 37 weeks of gestation (even if the preterm birth was following preterm rupture of membranes);
- •and / or late miscarriage or fetal loss (i.e. miscarriage or foetal loss between 14 and 22 weeks of gestation), even if one any of her last birth occurred at term.
- •Woman having a reliable connexion by phone
- •Woman who has understood the study process and objectives and agreed to sign an informed consent form;
- •affiliated to a social security regimen or equivalent.
- •Any eligible woman who will agree to participate in the study after being invited must sign a consent form before being included in the study. Women meeting all of these eligibility criteria will be invited even if they have oral or vaginal progestative treatment, cerclage or pessary, partially septate or arcuate uterus.
排除标准
- •- Woman of legal age under legal protection;
- •Women deprived of their freedom for administrative or legal reasons;
- •Woman who has not signed a consent form
- •Nulliparous;
- •Ectopic pregnancy;
- •Non-evolutive pregnancy or IUFD
- •Multiple pregnancy
- •Serious fetal malformation identified at first trimester screening such as cardiopathy, exencephaly, anasarque, gastroschisis, omphalocele, diaphragmatic hernia, cerebral or spinal major anomaly.
- •Woman participating in any clinical trial or intent to participate in another clinical trial, which may have an impact on flora or on prematurity rate, with or without investigational product at any time during the conduct of this study
- •Woman presenting contraindications to the study treatments: Hypersensitivity to the active substance or to any of the excipients
- •Woman presenting uterine malformation ( unicornuate, bicornuate, full septate)
- •Woman with preterm birth history because of twin pregnancy
- •Woman having received anti-infective treatment in the week preceding inclusion
研究组 & 干预措施
Group A: Screen-and-Treat Strategy
Patients are systematically screened for BV before 18 weeks' gestation by means of a vaginal swab analyzed by the innovative technique, whose result will be disclosed. If positive, appropriate treatment will be prescribed.
干预措施: Azithromycine (Drug)
Group A: Screen-and-Treat Strategy
Patients are systematically screened for BV before 18 weeks' gestation by means of a vaginal swab analyzed by the innovative technique, whose result will be disclosed. If positive, appropriate treatment will be prescribed.
干预措施: Ceftriaxone (Drug)
Group A: Screen-and-Treat Strategy
Patients are systematically screened for BV before 18 weeks' gestation by means of a vaginal swab analyzed by the innovative technique, whose result will be disclosed. If positive, appropriate treatment will be prescribed.
干预措施: Metronidazole (Drug)
Group A: Screen-and-Treat Strategy
Patients systematically screened for BV before 18 weeks' gestation by means of a vaginal swab analyzed by the innovative technique by PCR, whose result will be disclosed. If positive, appropriate treatment will be prescribed.
干预措施: Vaginal flora abnormalities screening and quantification using molecular biology technique (Diagnostic Test)
结局指标
主要结局
The rate of preterm birth
时间窗: Before 37 weeks of gestation
The primary endpoint will be the rate of preterm birth before 37 weeks of gestation, which will be compared between the innovative group and the standard group.
The rate of preterm birth
时间窗: From the enrollment to the delivery
The primary endpoint will be the rate of preterm birth before 37 weeks of gestation, which will be compared between the innovative group (Group A experimental) and the standard group (Group B Usual care).
The rate of preterm birth
时间窗: From the enrollment to the delivery date
The primary endpoint will be the rate of preterm birth before 37 weeks of gestation, which will be compared between the innovative group (Group A experimental) and the standard group (Group B Usual care).
次要结局
未报告次要终点