Fetal Growth RestrictionPhase 3EVUPACUSNCT06497959
Study of Placental Vascularization Using Contrast Ultrasound
A Phase 3 study testing SonoVue in people with Fetal Growth Restriction, run by Central Hospital, Nancy, France at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 64 years, women only
- Conditions the study is for
- Fetal Growth Restriction
- What is being tested?
- SonoVue
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteFrance
- Study dates
- 9 Apr 2025to 10 Apr 2029
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 64 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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).
Who cannot join
- 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:
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Juliette LEFEBVRE, Junior doctor contact
France1 site, 1 recruiting
- Recruiting
CHRU de NANCY
Nancy, 54000
Matthieu DAP, Doctor ofmedicine, 0033383343611, m.dap@chru-nancy.fr
About this study
Official title: Contribution of Contrast-Enhanced Ultrasound (CES) in the Fetal-placental Circulation Study
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.
Read more
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.
Read the detailed description
The primary objective is to compare placental contrast ultrasound in patients with medical termination of pregnancy at gestational age 16 weeks - 38 weeks+ 6 days between two groups: the fetal growth restriction one and the no fetal growth restriction.
Methods and analysis: This is a monocentric, prospective comparative, non-randomized, feasibility, open and interventional study. The investigators will include 30 women with medical termination of pregnancy divided in two groups: fetal growth restriction one and the no fetal growth restriction. Women are informed and recruited in the Fetal Medicine units in Nancy, over a period of 48 months.
- Conditions
- Fetal Growth Restriction
- Being tested
- SonoVue
- Keywords
- Contrast-Enhanced Ultrasound (CES)
- Medical subject headings
- Fetal Growth Retardation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SonoVueDrug
Placental contrast ultrasound using SonoVue by maternal intravenous injection
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: SonoVue |
| Severe growth restriction group | Experimental | Severe growth restriction defined by an estimated fetal weight below the 3rd percentile on ultrasound Receives: Drug: SonoVue |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 1 day
Secondary outcomes (4)
Measurement of the vascularization parameters of the Inter-Villi Space: infusion kinetics.
Measurement of the vascularization parameters of the Inter-Villi Space : infusion kinetics by ultrasound with a contrast agent: SonoVue ®.
Measured: 1 day
Measurement of the vascularization parameters of the umbilical cord: infusion kinetics
Measurement of the vascularization parameters of the umbilical cord: infusion kinetics by ultrasound with a contrast agent: SonoVue ®.
Measured: 1 day
Measurement of the placenta vascularization using histological analysis
Measurement of the placenta vascularization using histological analysis according to the Amsterdam Standardised Analysis criteria.
Measured: 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.
Measurement of the placenta vascularization using histological analysis according to the Amsterdam Standardised Analysis criteria and the vascularization parameters of the umbilical cord: infusion kinetics by ultrasound with a contrast agent: SonoVue ®.
Measured: through study completion, on average of 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2024
- Study start9 Apr 2025
- Primary completion9 Apr 2029 (estimated)
- Study completion10 Apr 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Fetal Growth RestrictionStudies of the same condition, open and under way.
- More trials run by Central Hospital, Nancy, FranceThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Central Hospital, Nancy, France
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Matthieu DAP, Central Hospital, Nancy, France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06497959
- Sponsor's protocol ID
- 2021PI062
- Other IDs
- 2023-506936-34-00, 2023
- Acronym
- EVUPACUS
- Status last verified
- Apr 2026
- First submitted
- 20 Jun 2024
- Last updated
- 7 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data (IPD) will be made available upon reasonable request, after de-identification. Additional documents such as the statistical analysis plan may also be available. Data will be available starting 3 months after publication and for a period of 5 years. Researchers must submit a methodologically sound proposal reviewed and approved by an independent ethics committee. Data will be shared via a secure online platform and under a data access agreement. Requests should be addressed to the corresponding author: Dr. Matthieu Dap (m.dap@chru-nancy.fr)
Publications
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.
PubMed 40784773
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Contribution of Contrast-Enhanced Ultrasound (CES) in the Fetal-placental Circulation Study
- ClinicalTrials.gov ID
- NCT06497959
- Acronym / sponsor ID
- EVUPACUS / 2021PI062
- Conditions
- Fetal Growth Restriction
- Keywords
- Contrast-Enhanced Ultrasound (CES)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Central Hospital, Nancy, FranceUniversity, hospital or other
- Study start
- 9 Apr 2025 (actual)
- Primary completion
- 9 Apr 2029 (estimated)
- Study completion
- 10 Apr 2029 (estimated)
- First posted
- 12 Jul 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The primary objective is to compare placental contrast ultrasound in patients with medical termination of pregnancy at gestational age 16 weeks - 38 weeks+ 6 days between two groups: the fetal growth restriction one and the no fetal growth restriction.
Methods and analysis: This is a monocentric, prospective comparative, non-randomized, feasibility, open and interventional study. The investigators will include 30 women with medical termination of pregnancy divided in two groups: fetal growth restriction one and the no fetal growth restriction. Women are informed and recruited in the Fetal Medicine units in Nancy, over a period of 48 months.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Non-growth restriction group (control group) | Experimental | Drug: SonoVueFetuses not affected by growth pathology, defined by an estimated weight greater than the 10th percentile at ultrasound |
| Severe growth restriction group | Experimental | Drug: SonoVueSevere growth restriction defined by an estimated fetal weight below the 3rd percentile on ultrasound |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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,
Key exclusion criteria (11 listed)
- Person who do not speak French
- Any medical condition contraindicating the administration of SonoVue, in particular:
- Persons covered by articles L. 1121-5, L. 1121-7 and L1121-8 of the French Public Health Code:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SonoVuePlacental contrast ultrasound using SonoVue by maternal intravenous injection | Drug | Non-growth restriction group (control group), Severe growth restriction group |
Primary outcome
The measurement of signal strength
Time frame: 1 day
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
4 secondary outcomes
Measurement of the vascularization parameters of the Inter-Villi Space: infusion kinetics.
Time frame: 1 day
Measurement of the vascularization parameters of the umbilical cord: infusion kinetics
Time frame: 1 day
Measurement of the placenta vascularization using histological analysis
Time frame: 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.
Time frame: through study completion, on average of 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2026.
- Background: PubMed 40784773Lefebvre 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.
- Individual participant dataSharing planned: Yes. Individual participant data (IPD) will be made available upon reasonable request, after de-identification. Additional documents such as the statistical analysis plan may also be available. Data will be available starting 3 months after publication and for a period of 5 years. Researchers must submit a methodologically sound proposal reviewed and approved by an independent ethics committee. Data will be shared via a secure online platform and under a data access agreement. Requests should be addressed to the corresponding author: Dr. Matthieu Dap (m.dap@chru-nancy.fr)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Juliette LEFEBVRE, Junior doctor contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing SonoVue in people with Fetal Growth Restriction, run by Central Hospital, Nancy, France at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 7 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Matthieu DAP, Doctor (+333 83 34 36 11, m.dap@chru-nancy.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The measurement of signal strength (time frame: 1 day). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06497959, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Apr 2026.