NCT04502823

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,088

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Sep 2020

Typical duration for not_applicable

Geographic Reach
1 country

20 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 4, 2020

Completed
2 days until next milestone

First Posted

Study publicly available on registry

August 6, 2020

Completed
2 months until next milestone

Study Start

First participant enrolled

September 21, 2020

Completed
2.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 18, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 18, 2022

Completed
Last Updated

February 21, 2024

Status Verified

July 1, 2021

Enrollment Period

2.2 years

First QC Date

August 4, 2020

Last Update Submit

February 20, 2024

Conditions

Fetal Growth Retardation

Outcome Measures

Primary Outcomes (1)

  • Adverse perinatal outcomes

    Cesarean delivery for non-reassuring fetal status or neonatal acidosis (artery cord potential of hydrogen (pH) \<7.15 + base excess \> -12 milliequivalent/L)

    4-6 weeks

Secondary Outcomes (12)

  • Rate of elective delivery

    4-6 weeks

  • Rate of Cesarean delivery

    4-6 weeks

  • Rate of Induction of labor

    4-6 weeks

  • Rate of neonatal admission in intensive care unit

    4-6 weeks

  • Time of neonatal admission in intensive care unit

    4-6 weeks

  • +7 more secondary outcomes

Study Arms (2)

Control Group

NO INTERVENTION

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.

Intervention Group

EXPERIMENTAL

Management based on sFlt-1/PlGF values

Procedure: Management based on sFlt-1/PlGF values

Interventions

Management based on sFlt-1/PlGF valuesPROCEDURE

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 Group

Eligibility Criteria

Age16 Years+
Sexfemale(Gender-based eligibility)
Gender Eligibility Detailspregnant women
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

  • Major fetal malformations or genetic disorders.
  • Fetal death.
  • Absent or reverse end-diastolic flow in umbilical artery Doppler or DV PI\>95th centile.
  • Non-reassuring cardiotocography (CTG).
  • Preeclampsia.
  • Diminished fetal movements.
  • Biophysical profile ≤ 6.
  • Oligohydramnios
  • Refusal to give informed consent.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (20)

Hospital Universitario de A Coruña

A Coruña, Spain

Location

Hospital General de Alicante

Alicante, Spain

Location

Hospital Germans Trias i Pujol

Badalona, Spain

Location

Hospital Universitari Vall d'hebron

Barcelona, Spain

Location

Hospital Universitario de Cabueñes

Cabueñes, Spain

Location

Hospital Universitario Puerta del Mar

Cadiz, Spain

Location

Hospital General Universitario de Elche

Elche, Spain

Location

Hospital Universitario de Getafe

Getafe, Spain

Location

Hospital Universitari Doctor Josep Trueta

Girona, Spain

Location

Hospital Sant Joan de Deu de Manresa

Manresa, Spain

Location

Hospital Clínico Universitario Virgen de la Arrixaca

Murcia, Spain

Location

Hospital Son Llàtzer

Palma de Mallorca, Spain

Location

Consorci Corporació Sanitària Parc Taulí de Sabadell

Sabadell, Spain

Location

Hospital Universitario Nuestra Señora de Candelaria

Santa Cruz de Tenerife, Spain

Location

Hospital Universitario Virgen de Valme

Seville, Spain

Location

Hospital Universitari Joan XXIII

Tarragona, Spain

Location

Hospital de Terrassa

Terrassa, Spain

Location

Hospital Universitari Mútua Terrassa

Terrassa, Spain

Location

Hospital Universitario de Torrejon

Torrejón de Ardoz, Spain

Location

Hospital Clinico Universitario Lozano Blesa

Zaragoza, Spain

Location

Related Publications (2)

  • 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.

    PMID: 39775039DERIVED

  • 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.

    PMID: 36222789DERIVED

MeSH Terms

Conditions

Fetal Growth Retardation

Condition Hierarchy (Ancestors)

Fetal DiseasesPregnancy ComplicationsFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesGrowth DisordersPathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • Manel Mendoza, PhD

    Vall d'hebron Institut de Recerca

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 4, 2020

First Posted

August 6, 2020

Study Start

September 21, 2020

Primary Completion

December 18, 2022

Study Completion

December 18, 2022

Last Updated

February 21, 2024

Record last verified: 2021-07

Locations

ES(20)