A Double-blind, Placebo-controlled Multicenter Trial on the Effect of Clindamycin and a Live Biotherapeutic on the Reproductive Outcomes of IVF Patients With Abnormal Vaginal Microbiota
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 333
- 试验地点
- 4
- 主要终点
- Rate of clinical pregnancy per embryo transfer
研究概览
简要总结
Study question: Does antibiotic alone or in combination with live biotherapeutic treatment of an abnormal vaginal microbiota improve the reproductive outcomes of IVF couples?
Study hypothesis:
The investigator hypothesize that treatment of the reproductive tract pathogens and restoration of vaginal Lactobacillus will improve the reproductive outcomes of IVF patients.
What is known already? Ultra-deep sequencing methods enable the refinement of reproductive tract microbiology in infertile patients. A recent meta-analysis reported that 19% of infertile patients had abnormal vaginal microbiota Moreover, someone have detected the presence of a Gardnerella (G.) vaginalis dominated endometrial biofilm in 50% of non-infertile patients with abnormal vaginal microbiota undergoing curettage; thus the treatment of such an endometrial biofilm might play an important role for the endometrial receptivity and subsequently the clinical pregnancy rate.
Pilot study: In a recent pilot study it was observed that an abnormal vaginal microbiota negatively affects the clinical pregnancy rate in IVF patients. In this study the prevalence of abnormal vaginal microbiota was 28% (36/130) and only 9% of patients with qPCR defined abnormal vaginal microbiota obtained a clinical pregnancy (p=0.004). This association remained significant in an adjusted analysis. Furthermore, the invetigators have preliminary results demonstrating that vaginal bacteria such as G. vaginalis can be found in the endometrium of IVF patients, which is also supported by recent publications
What is the novelty of this study? To the investigators knowledge, no previous treatment study of abnormal reproductive tract microbiota has been performed in IVF patients; this relatively small intervention holds the potential to increase the baby-take-home rate after IVF treatment.
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
- Triple (Participant, Care Provider, Investigator)
盲法说明
Moreover, an interim analysis will be performed by blinded outcomes assessors according to the primary outcome.
入排标准
- 年龄范围
- 18 Years 至 42 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Abnormal vaginal microbiota.
- •The screening swab should be repeated if more than 3 months old.
- •HIV, Hepatitis B or C positivity.
- •First, second or third IVF stimulation cycle or embryo transfer therefrom.
- •Written informed consent.
排除标准
- •Known or suspected hypersensitivity to clindamycin.
- •HPV CIN 2 or higher.
- •Former or current inflammatory bowel disease
- •Severe concomitant disease, including diabetes.
- •MAX 2 embryos may be transferred
- •Artificial heart valve
- •Intrauterine malformations with operation indication as determined by treating physician (Polyps, Septum, fibroma)
研究组 & 干预措施
Clindamycin + LACTIN-V (L.crispatus)
Oral Clindamycin 300 mg 2 times per day for 7 days followed by LACTIN-V (Osel, Inc.) until completion of the clinical pregnancy scan at week 7-9.
干预措施: Clindamycin (Drug)
Clindamycin + placebo LACTIN-V
Oral Clindamycin 300 mg 2 times per day for 7 days followed by LACTIN-V placebo (Osel, Inc.) until completion of the clinical pregnancy scan at week 7-9.
干预措施: Clindamycin (Drug)
Placebo clindamycin + placebo LACTIN-V
Matching clindamycin placebo 2 times per day for 7 days followed by LACTIN-V placebo (Osel Inc.) until completion of the clinical pregnancy scan at week 7-9.
干预措施: Placebo (Other)
结局指标
主要结局
Rate of clinical pregnancy per embryo transfer
时间窗: 7-9 weeks
Ultrasound scan detection of intrauterine fetal heartbeat in gestational week 7-9
次要结局
- Live birth rate(25-42 weeks depending on pregnancy.)
- Biochemical pregnancy(14 days gestation)
- Implantation rate(pregnancy scan at 7-9 weeks)
- Number of late miscarriage(12 weeks gestation - to labour (i.e. not including still birth))
- Cure of abnormal vaginal microbiota(1-2 months)
- early miscarriage(14 days - 12 weeks gestation)
- Number of preterm birth(prior to 37 gestational weeks)
- Birth weight(25-42 weeks gestation depending on pregnancy)
研究者
Peter Humaidan
Professor, MD
Regionshospitalet Viborg, Skive