Preterm Premature Rupture of Fetal Membranes: Cervical Ultrasound and Biological Markers to Diagnose Prematurity (RECHOBIOL) (RECHOBIOL)

Preterm Premature Rupture of Fetal Membranes: Cervical Ultrasound and Biological Markers to Diagnose Prematurity.

Our main hypothesis is to consider that the detection of biomarkers on admission combined with the length of the cervix would improve the prediction of the latency period in case of preterm premature rupture of membranes (pPROM). The primary purpose of the protocol is to assess the performance of these tests to predict a latency period <48 hours in case of pPROM.

Study Overview

• Status: Recruiting
• Conditions: Premature Rupture of Membrane
• Intervention / Treatment: Diagnostic test: Vaginal secretions collection; Diagnostic test: Blood sample

Detailed Description

Preterm premature rupture of membranes (pPROM) is defined as a spontaneous rupture before the start of labor ("premature" rupture) and before 37 weeks of gestation ("preterm"). pPROM concern 2-3% of pregnancies. It is the main cause of prematurity since it is responsible for 24 to 42% of preterm deliveries. The time between PROM and childbirth is named the latency period. Its total duration can vary from a few hours to several weeks. Childbirth occurs within 48 hours of rupture for 18 to 93% of cases, within 7 days for 56 to 96% and within 28 days for 78 to 100%. The earlier PROM occurs during pregnancy, the longer the latency period is. The factors associated with a shorter latency period are: cervical changes during admission for pPROM, a shortened cervix on ultrasound or a threat of premature delivery prior to PROM, the existence of uterine contractions, oligoamnios, and the occurrence of a materno-fetal complication of pPROM.

In a pPROM situation, a prolonged latency period improves the neonatal prognosis by increasing the gestational age of birth, gives the possibility of administering the corticosteroid treatment of fetal pulmonary maturation and also allows an in utero transfer in an adapted maternity.

Several studies have shown a correlation between the length of the cervix during rupture and the latency period in the context of pPROM.

To date, there are no effective biomarkers used in current practice to predict this latency period.

We want to assess the diagnostic performance of different vaginal (PIBF / PP14 / IGFBP1 native and total) and serum (PIBF / MIF) markers as well as the ultrasound length of the cervix to predict the duration of this latency period in order to better anticipate the risk of prematurity.

• Study Type: Interventional
• Enrollment (Anticipated): 170
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Clermont-Ferrand, France, 63000
    • Recruiting
    • CHU de Clermont-Ferrand

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Parturient admitted to the Clermont-Ferrand Hospital maternity for preterm premature rupture of membranes between 24+0 and 36+4 gestation week.
• Capacity to give informed consent.
• Coverage by a French social security scheme.

Exclusion Criteria:

• Refusal to participate
• pPROM formally occurred more than 24 hours ago (free flow or positive breakage test)
• Cervical dilatation ≥ 4 cm
• Multiple Pregnancy
• Known uterine malformation
• Fetal Malformation
• Placenta previa
• Abundant metrorrhagia
• Patient under guardianship or curatorship

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Eligible patients who had consented to participate; Eligible patients who had consented to participate to the study, namely parturient admitted to the Clermont-Ferrand Hospital maternity for preterm premature rupture of membranes between 24+0 and 36+4 gestation week with cervical dilation < 4cm and without known uterine malformation, fetal malformation, placenta previa or abundant metrorrhagia. Patients underwent vaginal swabbing and blood sample collection at the admission.

Diagnostic test: Vaginal secretions collection; Vaginal secretions are collected under speculum with a swab (10 seconds of impregnation of the swab). The swab is immersed in a tube containing an extraction buffer for 10 seconds. The tube is mixed and sent to the laboratory for subsequent analysis of biomarkers (IGFBP1 T/N, PIBF, PP14) and storage.; Diagnostic test: Blood sample; 2 tubes of blood sample were collected and sent to the laboratory for serum storage and biomarkeurs assay (PIBF and MIF)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
total IGFBP1 in vaginal secretion at admission	Results of the tests detecting total IGFBP1 (positive/ negative)	Day 0
native IGFBP1 in vaginal secretion at admission	Results of the tests detecting native IGFBP1 (positive/ negative)	Day 0
PP14 in vaginal secretion at admission	PP14 values in vaginal secretion at admission dosed using the ELISA technique	Day 0
PIBF in vaginal secretion at admission	PIBF values in vaginal secretion at admission dosed using the ELISA technique	Day 0
PIBF in maternal serum at admission	PIBF values in maternal serum at admission dosed using the ELISA technique	Day 0
MIF in maternal serum at admission	MIF values in maternal serum at admission dosed using the ELISA technique	Day 0
Ultrasound length of cervix measured at the admission	Length of cervix was maesured by ultrasound at the admission (millmeters)	Day 0

Collaborators and Investigators

• Sponsor: University Hospital, Clermont-Ferrand
• Collaborators: Biosynex Company

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 10, 2020
• Primary Completion (ANTICIPATED): March 1, 2023
• Study Completion (ANTICIPATED): March 1, 2023

Study Registration Dates

• First Submitted: January 17, 2020
• First Submitted That Met QC Criteria: January 17, 2020
• First Posted (ACTUAL): January 23, 2020

Study Record Updates

• Last Update Posted (ACTUAL): March 16, 2020
• Last Update Submitted That Met QC Criteria: March 12, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Biomarkers; Predictive Value of Tests; Preterm premature rupture of membranes; Latency period
• Additional Relevant MeSH Terms: Wounds and Injuries; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Rupture; Premature Birth; Fetal Membranes, Premature Rupture
• Other Study ID Numbers: RBHP 2019 GALLOT; 2019-A02306-51 (OTHER: ANSM)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No