Clotrimazole for Bacterial vaginosis | High-risk pregnancy at risk of preterm birth | Vaginal flora abnormalities (vaginal dysbiosis)

Inclusion criteria

• {"criterion_text":"- Pregnant women over 18 years of age\n- 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\n- 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\n- Woman Affiliated to a social security regimen or equivalent"}

Exclusion criteria

• {"criterion_text":"- Woman of legal age under legal protection\n- Adult patient under guardianship or trusteeship, patient deprived of liberty\n- Nulliparous\n- Multiple pregnancy (twins, triplet or more)\n- Serious fetal malformation identified at first trimester screening such as cardiopathy, exencephaly, anasarque, gastroschisis, omphalocele, and diaphragmatic hernia, cerebral or spinal major anomaly.\n- Woman presenting uterine malformation (unicornuate, bicornuate, full septate)\n- Woman with preterm birth history because of twin pregnancy\n- 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\n- Woman having received anti-infective treatment in the week preceding inclusion\n- Woman presenting contraindications to the study treatments, in particular hypersensitivity to the active substance or to any of the excipients.\n- Ectopic pregnancy\n- Non-evolutive pregnancy or intrauterine fetal demise/death leading to preterm birth without other preterm birth\n- Woman with only history of preterm birth because of preeclampsia or intrauterine growth restriction but without a history of preterm birth before 37 weeks of gestation or late miscarriage (high-risk preterm birth population between 14 and 22 weeks of gestation)\n- Woman with history of preterm birth or voluntary fetal abortion or fetal abortion for medical indication but without a history of preterm birth before 37 weeks of gestation or late miscarriage (high-risk preterm birth population between 14 and 22 weeks of gestation).\n- Woman for who the history of preterm birth before 37 weeks of gestation or late miscarriage history is due to intra uterine demise before labor or voluntary abortion"}

Primary endpoints

• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Occurrence (rate) of delivery before 37 weeks' gestation compared between Group A (screen-and-treat) and Group B (usual care). Measured as rate of preterm birth <37 weeks of gestation."}

Secondary endpoints

• {"endpoint_text":"- Severity criteria of prematurity: the rates of delivery before 23, 24, 26, 28, 32 and 37 weeks of gestation\n- Morbidity during pregnancy: The rate of preterm rupture of the membranes defined as clean break with evident flow of amniotic fluid and/or a positive Amnicator, AmniSure, Actim PROM (IGFBP-1) test\n- Morbidity during pregnancy: The rate of late fetal loss ( name also late miscarriage) between 14 and 22 weeks of gestation\n- Morbidity during pregnancy: The rate of fetal growth restriction defined as an abdominal and/or femoral circumference measurement < 5th percentile for the gestational age according to OMS\n- Morbidity during pregnancy: The rate of endometritis characterized by a uterus that is painful on mobilization, the presence of purulent vaginal discharge (with the presence of altered leukocytes on vaginal swabbing) and hyperthermia >38°C requiring antibiotic therapy (with a negative result upon cytobacteriologic examination of the urine)\n- Morbidity during pregnancy: The rate of spontaneous preterm birth calculated as follows: patients with caesarean section or labor induced before 37 weeks’ gestation for any of the following reasons: preeclampsia, retroplacental hematoma, fetal heart rhythm abnormality, fetal growth restriction or in utero fetal death of vascular origin, medical termination of pregnancy for fetal malformation or chromosomal abnormalities will be excluded from this adjusted preterm birth rate\n- Morbidity during pregnancy: The rate of risk of preterm birth defined by uterine contractions occurring before 37 weeks’ gestation and/or a cervical length of less than 25 mm on vaginal ultrasound\n- Morbidity during pregnancy: The rate of progestative treatment\n- Morbidity during pregnancy: The rate of emergency cerclage\n- Total inpatient stay: the total length, antepartum and postpartum, of hospitalization for mother and newborn in number of days (including conventional hospitalization, day hospitalization and hospitalization at home, hospitalization in neonatology or intensive care unit)\n- Neonatal mortality: the rate of death after 22 weeks’ gestation and until hospital discharge\n- Neonatal morbidity, which will be compared between the innovative group and the standard group until hospital discharge, by the occurrence of the following clinical events: respiratory distress syndrome, bronchopulmonary dysplasia, rate of `intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, sepsis, retinopathy of prematurity, newborns admitted to intensive care unit, mechanical ventilation, length of stay in intensive care unit.\n- The rate of spontaneous abortion before 14 weeks’ gestation (13 weeks and 6 days) and before 22 week's gestation.\n- In Group A: The effectiveness of the treatment will be assessed by comparing the quantitative loads of hosts quantified by molecular biology before and after treatments.\n- In group A: The rate of successful treatment (determined by a negative molecular analysis at the first vaginal sample control)\n- In group A: The rate of recurrence will be determined by molecular analysis during follow-up of positive patients and defined as a positive result after a negative result control in this group of patients.\n- In group A: the rate of positivity for each host before and after treatments\n- In group A: The rate of preterm birth of women with an initial success of treatment (based on a negative result for the screening test conducted for recurrence)\n- In group A: The rate of preterm birth among women with either a positive POC or a negative POC test\n- In group A: The rate of preterm birth according to the results of POC and the specy\n- In group B: The proportion, type of screening and management of BV and its recurrence detected by traditional methods (Nugent score, etc.) for the standard strategy. The proportion of women under 25 years or at risk of sexual transmitted infection, positive for C. trachomatis.\n- Health economic: Incremental cost-effectiveness ratio\n- Health economic: Budget impact\n- Health economic: Indicators of process\n- Exploratory: description of the metagenomic and culturomic analysis performed on a sample of patients.","definition_or_measurement_approach":"Includes multiple pregnancy and neonatal morbidity/mortality measures defined in endpoint descriptions: severity by gestational age cut-offs; PROM defined by clinical criteria and specific tests (Amnicator, AmniSure, Actim PROM); fetal growth restriction defined as abdominal/femoral circumference <5th percentile per WHO; spontaneous preterm birth definition excludes indicated preterm deliveries for listed reasons; neonatal outcomes measured until hospital discharge; health economic endpoints measured as ICER and budget impact; microbiological endpoints assessed by molecular biology (quantitative loads, molecular analysis for recurrence)."}

France

Earliest CTIS Part Ii Submission Date

17-02-2026

Latest Decision Or Authorization Date

01-04-2026

Processing Time Days

43

Number Of Sites

22

Number Of Participants

1794

Primary sponsor

Full Name

Assistance Publique Hopitaux De Marseille

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France