Study of Placental Vascularization Using Contrast Ultrasound

NCT06497959 | Recruiting Phase 3

• 2 other identifiers: 2021PI0622023-506936-34-00
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Preeclampsia and intrauterine growth restriction (IUGR) are two principal complications of pregnancy. These diseases are related to placental dysfunction nevertheless knowledge of its pathophysiological mechanisms remains inadequate. No etiological treatment for these pathologies is available. Inducing birth is the only way to prevent the occurrence of these complications (such as fetal death in utero. Therefore, a better understanding of placental vascularization under pathological and physiological conditions is necessary. This placental vascularization evolves throughout gestation. Histological studies have improved our knowledge of placental vascular pathologies; however, these are ex vivo data that only provide an incomplete reflection of placental function. In vivo placental studies are therefore essential to understand the mechanisms of placental perfusion. Currently, these studies are limited because the available tools (such as placental Doppler) do not allow for the separate study of maternal placental flow from fetal flow. However, histological evidence clearly establishes maternal placental vascular involvement in IUGR. It would therefore be interesting to study maternal and fetal placental vascularization separately. The development of new in vivo imaging exploration techniques will help to better understand placental pathologies. In obstetrics, CES would offer the opportunity to study in vivo placental vascularization in a segmented manner (maternal versus fetal side independently) since the microbubbles do not cross the placental barrier. Animal studies show no toxic effects on fetal development nor any crossing of the placental barrier. In humans, the innovative use of this contrast agent has allowed for a better understanding of placental vascularization in the first trimester of pregnancy.

Conditions

Fetal Growth Restriction

Keywords

Contrast-Enhanced Ultrasound (CES)

Outcome Measures

Primary Outcomes (1)

• The measurement of signal strength

  The measurement of signal strength (in arbitrary units) in the Inter-Villi Space of the placetna ,obtained by contrast ultrasound, in women who have confirmed a medical termination of pregnancy according to the group defined by fetal weight in percentile as a function of term. Severe Intrauterine Growth Restriction (IUGR) is defined as a weight below the 3rd percentile for gestational age.For each group, these parameters will be obtained by qualitative analysis (i.e. presence/absence of contrast medium passage) and semi-quantitative analysis (enhancement percentage, area under the curve, time to peak, slopes -wash-in rate and wash-out rate, etc.) using dedicated software VueBox, BRACCO

  1 day

Secondary Outcomes (4)

• Measurement of the vascularization parameters of the Inter-Villi Space: infusion kinetics.

  1 day

• Measurement of the vascularization parameters of the umbilical cord: infusion kinetics

  1 day

• Measurement of the placenta vascularization using histological analysis

  through study completion, on average of 24 months

• Comparison of of the placenta vascularization using histological analysis and the measurement of the vascularization parameters of the Inver-Villi Space.

  through study completion, on average of 24 months

Study Arms (2)

Non-growth restriction group (control group)

EXPERIMENTAL

Fetuses not affected by growth pathology, defined by an estimated weight greater than the 10th percentile at ultrasound

Drug: SonoVue

Severe growth restriction group

EXPERIMENTAL

Severe growth restriction defined by an estimated fetal weight below the 3rd percentile on ultrasound

Drug: SonoVue

Interventions

SonoVue DRUG

Placental contrast ultrasound using SonoVue by maternal intravenous injection

Non-growth restriction group (control group); Severe growth restriction group

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Adult woman (age ≥18 years),
• Gestational age between 16 GW + 0 days and 38 GW + 6 days,
• Singleton pregnancy,
• Whose request of a medical termination of pregnancy (IMG) has been formulated and accepted in a written form by the Centre Pluridisciplinaire de Diagnostic Prénatal (CPDPN) of the Centre Hospitalier Régional Universaitaire (CHRU) de Nancy,
• Affiliated to the social security system or benefit from such a system,
• Having received full information and having signed an informed consent form.
• Criteria specific to patients in the "growth restriction" group:
• \- Severe growth restriction defined by an estimation of foetal weight below the 3rd percentile using ultrasound performed no more than 15 days prior to the IMG (the diagnosis must be established at the time of the request for IMG in routine care).

You may not qualify if:

• Person who do not speak French
• Any medical condition contraindicating the administration of SonoVue, in particular:
• Hypersensitivity to sulfur hexafluoride or to one of the other components of SonoVue® such as polyethylene glycol (PEG),
• Women with recent acute coronary syndrome or unstable ischaemic heart disease,
• Women with a right-to-left shunt, severe pulmonary arterial hypertension (pulmonary arterial pressure \> 90 mmHg), uncontrolled systemic hypertension and women suffering from respiratory distress syndrome.
• Persons covered by articles L. 1121-5, L. 1121-7 and L1121-8 of the French Public Health Code:
• Breast-feeding mother
• Minor (not emancipated)
• An adult subject to a legal protection (guardianship, curatorship, safeguard of justice)
• An adult unable to give consent
• Persons deprived of their liberty by a judicial or administrative decision, persons under psychiatric care by virtue of articles L. 3212-1 and L. 3213-1

Sponsors & Collaborators

• Central Hospital, Nancy, France: lead

Study Sites (1)

CHRU de NANCY

Nancy, 54000, France

RECRUITING

Related Publications (1)

• Lefebvre J, Cherifi A, Hossu G, Fijean AL, Morel O, Bertholdt C, Beaumont M, Dap M. Contributions of contrast-enhanced ultrasound (CEUS) to a fetal-placental circulation study (EVUPACUS): a protocol for a prospective comparative study in a population of women undergoing termination of pregnancy. BMJ Open. 2025 Aug 10;15(8):e093090. doi: 10.1136/bmjopen-2024-093090.

  PMID: 40784773 DERIVED

MeSH Terms

Conditions

Fetal Growth Retardation

Interventions

contrast agent BR1

Condition Hierarchy (Ancestors)

Fetal Diseases; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Growth Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Matthieu DAP, Doctor

CONTACT

+333 83 34 36 11; m.dap@chru-nancy.fr

Juliette LEFEBVRE, Junior doctor

CONTACT

J.LEFEBVRE@chru-nancy.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Doctor in medicine (Gynaecologist-Obstetrician)

Study Record Dates

• First Submitted: June 20, 2024
• First Posted: July 12, 2024
• Study Start: April 9, 2025
• Primary Completion (Estimated): April 9, 2029
• Study Completion (Estimated): April 10, 2029
• Last Updated: May 31, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share

Locations

FR (1)