AUTOP 2 : Screen-and-treat strategy for vaginal flora abnormalities by molecular biology in pregnant women at high risk of preterm birth: A Multicentre, Randomized Study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Marseille

Participant type

Patients

Age range

18-64 years

Gender

Female

Therapeutic area

Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13], Diseases [C] - Bacterial Infections and Mycoses [C01]

Decision date (initial)

2026-04-01

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

DGOS - PHRC 2022-0168

External identifiers

EU CT number

2023-509421-41-03

ClinicalTrials.gov

NCT06349122

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Diagnosis, Therapy

Evaluate the effectiveness of an innovative screen-and-treat strategy for vaginal flora abnormalities by molecular biology using POC multiplex technology before 18 weeks’ gestation to reduce the rate of preterm birth in a population of pregnant women at high risk of preterm birth (with previous history of preterm birth or late fetal loss), in comparison with a usual strategy with absence of screening.

Secondary objectives 15

1. The preterm birth rate after 22 week's gestation
2. The severity of prematurity according with early gestational age at birth
3. The morbidity during pregnancy
4. The total inpatient stay of the mother and the newborn
5. The neonatal mortality and morbidity at the end of hospitalization
6. The spontaneous abortion rate between 14 weeks' gestation (13 and 6 days) and before 22 week's gestation
7. In Group A: To determine the effectiveness of the personalized treatment on the flora and on the targeted microorganism using PCR
8. In Group A: To describe the frequency of POC positivity recurrence
9. In Group A: To determine the risk of preterm birth of women with an initial success of treatment
10. In group A: To compare the risk of preterm birth between women with or without vaginal dysbiosis or infection (i.e. to compare the risk of preterm birth with a Positive POC or a negative POC)
11. In Group A: To compare the risk of preterm birth according to the results of POC and the specy
12. In Group B: To describe the frequency/type of real-life diagnosis for BV (using conventional methods), screening for recurrence and treatments.
13. Health economic objective: To assess the cost-effectiveness of the Screen-and-Treat strategy compared with usual care
14. Health economic objective: to conduct a budgetary impact analysis of the innovation
15. Exploratory objective: To perform a metagenomic and culturomic analysis on a sample of patients

Conditions and MedDRA coding

Bacterial vaginosis

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Pregnant women over 18 years of age
2. 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
3. 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
4. Woman Affiliated to a social security regimen or equivalent

Exclusion criteria 15

1. Woman of legal age under legal protection
2. Adult patient under guardianship or trusteeship, patient deprived of liberty
3. Nulliparous
4. Multiple pregnancy (twins, triplet or more)
5. Serious fetal malformation identified at first trimester screening such as cardiopathy, exencephaly, anasarque, gastroschisis, omphalocele, and diaphragmatic hernia, cerebral or spinal major anomaly.
6. Woman presenting uterine malformation (unicornuate, bicornuate, full septate)
7. Woman with preterm birth history because of twin pregnancy
8. 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
9. Woman having received anti-infective treatment in the week preceding inclusion
10. Woman presenting contraindications to the study treatments, in particular hypersensitivity to the active substance or to any of the excipients.
11. Ectopic pregnancy
12. Non-evolutive pregnancy or intrauterine fetal demise/death leading to preterm birth without other preterm birth
13. 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)
14. 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).
15. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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)

Secondary endpoints 25

1. Severity criteria of prematurity: the rates of delivery before 23, 24, 26, 28, 32 and 37 weeks of gestation
2. 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
3. Morbidity during pregnancy: The rate of late fetal loss ( name also late miscarriage) between 14 and 22 weeks of gestation
4. 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
5. 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)
6. 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
7. 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
8. Morbidity during pregnancy: The rate of progestative treatment
9. Morbidity during pregnancy: The rate of emergency cerclage
10. 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)
11. Neonatal mortality: the rate of death after 22 weeks’ gestation and until hospital discharge
12. 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.
13. The rate of spontaneous abortion before 14 weeks’ gestation (13 weeks and 6 days) and before 22 week's gestation.
14. 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.
15. In group A: The rate of successful treatment (determined by a negative molecular analysis at the first vaginal sample control)
16. 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.
17. In group A: the rate of positivity for each host before and after treatments
18. 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)
19. In group A: The rate of preterm birth among women with either a positive POC or a negative POC test
20. In group A: The rate of preterm birth according to the results of POC and the specy
21. 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.
22. Health economic: Incremental cost-effectiveness ratio
23. Health economic: Budget impact
24. Health economic: Indicators of process
25. Exploratory: description of the metagenomic and culturomic analysis performed on a sample of patients.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Marseille

Sponsor organisation

Assistance Publique Hopitaux De Marseille

Address

80 Rue Brochier

City

Marseille

Postcode

13005

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Marseille

Contact name

Pr. Florence BRETELLE

Public contact point

Organisation

Assistance Publique Hopitaux De Marseille

Contact name

Pr. Florence BRETELLE

Locations

1 EU/EEA country · 22 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications