Management of Fetal Growth Restriction at Term: Angiogenic Factors Versus Feto-placental Doppler

NCT ID: NCT04502823

Last Updated: 2024-02-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

1088 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-09-21

Study Completion Date

2022-12-18

Brief Summary

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Open randomized non-inferiority controlled trial to examine the use of angiogenic factors (instead of feto-placental Doppler) for fetal growth restriction at term to reduce the rate of labor inductions, without worsening perinatal outcomes.

Detailed Description

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Pregnant women with estimated fetal weight (EFW) \< 10th centile between 36+0 and 37+6 weeks of gestation (WG) will receive complete ultrasonographic assessment consisting of feto-placental Doppler, amniotic fluid measurement and biophysical profile assessment. The cases not meeting any exclusion criteria will be offered to participate in this trial. After giving their informed consent a blood sample will be drawn in all of them and they will undergo randomization into two arms.

1. Intervention arm: In women allocated to the intervention group, the soluble fms-like tyrosine kinase/placental growth factor (sFlt-1/PlGF) result will be revealed to the investigators that will act according to the results of sFlt/PlGF:

* Fetuses with sFlt-1/PlGF ≥38, elective delivery will be recommended at ≥37 weeks.
* Fetuses with sFlt-1/PlGF \<38, weekly follow up will be recommended until delivery (at ≥40 weeks).
2. Control arm: In women allocated to the control group, the sFlt-1/PlGF result will be blinded to caregivers. Routine Doppler-based clinical care will be used to counsel women. Following the Doppler classification:

* Fetuses with EFW below the 3rd centile or below the 10th centile accompanied by any impaired fetoplacental Doppler, elective delivery will be recommended at at ≥37 weeks.
* Fetuses with EFW above the 3rd centile without any fetoplacental Doppler abnormality, elective delivery will be recommended at at ≥40 weeks.

In both arms, fetuses will receive weekly follow-up from randomization to delivery consisting on feto-placental Doppler sFlt-1/PlGF and CTG. If any of the following is present at any time, earlier delivery will be recommended:

* sFlt-1/PlGF ≥38 (only in the intervention group),
* absent or reverse end-diastolic flow at the umbilical artery Doppler or DV PI\>95th centile
* non-reassuring CTG
* preeclampsia
* diminished fetal movements
* biophysical profile ≤ 6 or oligohydramnios (deepest pocket \<2 cm).

Conditions

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Fetal Growth Retardation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Control Group

Clinical practice: Management by Doppler and CTG findings.

In women allocated to the control group, the sFlt-1/PlGF result will be blinded to caregivers. Routine Doppler-based clinical care will be used to counsel women. Following the Doppler classification:

* Fetuses with an EFW below the 3rd centile or below the 10th centile accompanied by any impaired fetoplacental Doppler, elective delivery will be recommended immediately (within 24h) at ≥37 weeks.
* Fetuses with an EFW above the 3rd centile without any fetoplacental Doppler abnormality, elective delivery will be recommended at at ≥40 weeks.

Group Type NO_INTERVENTION

No interventions assigned to this group

Intervention Group

Management based on sFlt-1/PlGF values

Group Type EXPERIMENTAL

Management based on sFlt-1/PlGF values

Intervention Type PROCEDURE

In women allocated to the intervention group, the sFlt-1/PlGF result will be revealed to the investigators that will act according to the results of sFlt/PlGF:

* Fetuses with sFlt-1/PlGF ≥38, elective delivery will be recommended immediately (within 24h) at ≥37 weeks.
* Fetuses with sFlt-1/PlGF \<38 weekly follow up will be recommended and delivery at ≥40 weeks.

Interventions

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Management based on sFlt-1/PlGF values

In women allocated to the intervention group, the sFlt-1/PlGF result will be revealed to the investigators that will act according to the results of sFlt/PlGF:

* Fetuses with sFlt-1/PlGF ≥38, elective delivery will be recommended immediately (within 24h) at ≥37 weeks.
* Fetuses with sFlt-1/PlGF \<38 weekly follow up will be recommended and delivery at ≥40 weeks.

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

1. Pregnant women ≥ 16 years of age.
2. Singleton pregnancy.
3. Ultrasonographic estimated fetal weight \<10th centile.
4. Gestational age between 36+0 and 37+6 weeks.

Exclusion Criteria

1. Major fetal malformations or genetic disorders.
2. Fetal death.
3. Absent or reverse end-diastolic flow in umbilical artery Doppler or DV PI\>95th centile.
4. Non-reassuring cardiotocography (CTG).
5. Preeclampsia.
6. Diminished fetal movements.
7. Biophysical profile ≤ 6.
8. Oligohydramnios
9. Refusal to give informed consent.
Minimum Eligible Age

16 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Hospital Universitari Vall d'Hebron Research Institute

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Manel Mendoza, PhD

Role: PRINCIPAL_INVESTIGATOR

Vall d'hebron Institut de Recerca

Locations

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Hospital Universitario de A Coruña

A Coruña, , Spain

Site Status

Hospital General de Alicante

Alicante, , Spain

Site Status

Hospital Germans Trias i Pujol

Badalona, , Spain

Site Status

Hospital Universitari Vall d'hebron

Barcelona, , Spain

Site Status

Hospital Universitario de Cabueñes

Cabueñes, , Spain

Site Status

Hospital Universitario Puerta del Mar

Cadiz, , Spain

Site Status

Hospital General Universitario de Elche

Elche, , Spain

Site Status

Hospital Universitario de Getafe

Getafe, , Spain

Site Status

Hospital Universitari Doctor Josep Trueta

Girona, , Spain

Site Status

Hospital Sant Joan de Deu de Manresa

Manresa, , Spain

Site Status

Hospital Clínico Universitario Virgen de la Arrixaca

Murcia, , Spain

Site Status

Hospital Son Llàtzer

Palma de Mallorca, , Spain

Site Status

Consorci Corporació Sanitària Parc Taulí de Sabadell

Sabadell, , Spain

Site Status

Hospital Universitario Nuestra Señora de Candelaria

Santa Cruz de Tenerife, , Spain

Site Status

Hospital Universitario Virgen de Valme

Seville, , Spain

Site Status

Hospital Universitari Joan XXIII

Tarragona, , Spain

Site Status

Hospital de Terrassa

Terrassa, , Spain

Site Status

Hospital Universitari Mútua Terrassa

Terrassa, , Spain

Site Status

Hospital Universitario de Torrejon

Torrejón de Ardoz, , Spain

Site Status

Hospital Clinico Universitario Lozano Blesa

Zaragoza, , Spain

Site Status

Countries

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Spain

References

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Garcia-Manau P, Bonacina E, Martin-Alonso R, Martin L, Palacios A, Sanchez-Camps ML, Lesmes C, Hurtado I, Perez E, Tubau A, Ibanez P, Alcoz M, Valino N, Moreno E, Borrero C, Garcia E, Lopez-Quesada E, Diaz S, Broullon JR, Teixidor M, Chulilla C, Ferrer-Costa R, Gil MM, Lopez M, Ramos-Forner GM, Blanco JE, Moreno A, Lazaro-Rodriguez M, Vaquerizo O, Soriano B, Fabre M, Gomez-Valencia E, Cuina A, Alayon N, Sainz-Bueno JA, Vives A, Esteve E, Ocana V, Lopez MA, Maroto A, Carreras E, Mendoza M. Angiogenic factors versus fetomaternal Doppler for fetal growth restriction at term: an open-label, randomized controlled trial. Nat Med. 2025 Mar;31(3):1008-1015. doi: 10.1038/s41591-024-03421-9. Epub 2025 Jan 7.

Reference Type DERIVED
PMID: 39775039 (View on PubMed)

Garcia-Manau P, Mendoza M, Bonacina E, Martin-Alonso R, Martin L, Palacios A, Sanchez ML, Lesmes C, Hurtado I, Perez E, Tubau A, Ibanez P, Alcoz M, Valino N, Moreno E, Borrero C, Garcia E, Lopez-Quesada E, Diaz S, Broullon JR, Teixidor M, Chulilla C, Gil MM, Lopez M, Candela-Hidalgo A, Salinas-Amoros A, Moreno A, Morra F, Vaquerizo O, Soriano B, Fabre M, Gomez-Valencia E, Cuina A, Alayon N, Sainz JA, Vives A, Esteve E, Ocana V, Lopez MA, Maroto A, Carreras E. The Fetal Growth Restriction at Term Managed by Angiogenic Factors Versus Feto-Maternal Doppler (GRAFD) Trial to Avoid Adverse Perinatal Outcomes: Protocol for a Multicenter, Open-Label, Randomized Controlled Trial. JMIR Res Protoc. 2022 Oct 11;11(10):e37452. doi: 10.2196/37452.

Reference Type DERIVED
PMID: 36222789 (View on PubMed)

Other Identifiers

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PR(AMI)527/2019

Identifier Type: -

Identifier Source: org_study_id

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