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Fetal Growth RetardationGRAFDNCT04502823

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

A study testing Management based on sFlt-1/PlGF values in people with Fetal Growth Retardation, run by Hospital Universitari Vall d'Hebron Research Institute at 20 sites in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 16 years and older, women only
Conditions the study is for
Fetal Growth Retardation
What is being tested?
Management based on sFlt-1/PlGF values
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,088 participants
Where
20 sitesSpain
Study dates
21 Sep 2020to 18 Dec 2022
Phase
Interventional
Are there results?
None posted in the registry

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 16 years and older
  • Women only
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

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

Who cannot join

  • 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.
Show all 9Show fewer
  • Biophysical profile ≤ 6.
  • Oligohydramnios
  • Refusal to give informed consent.

Trial locations and contacts

20 sites in 1 country.

20 sites in 1 country

Spain20 sites

  • Hospital Universitario de A Coruña

    A Coruña

  • Hospital General de Alicante

    Alicante

  • Hospital Germans Trias i Pujol

    Badalona

  • Hospital Universitari Vall d'hebron

    Barcelona

  • Hospital Universitario de Cabueñes

    Cabueñes

  • Hospital Universitario Puerta del Mar

    Cadiz

  • Hospital General Universitario de Elche

    Elche

  • Hospital Universitario de Getafe

    Getafe

  • Hospital Universitari Doctor Josep Trueta

    Girona

  • Hospital Sant Joan de Deu de Manresa

    Manresa

  • Hospital Clínico Universitario Virgen de la Arrixaca

    Murcia

  • Hospital Son Llàtzer

    Palma de Mallorca

  • Consorci Corporació Sanitària Parc Taulí de Sabadell

    Sabadell

  • Hospital Universitario Nuestra Señora de Candelaria

    Santa Cruz de Tenerife

  • Hospital Universitario Virgen de Valme

    Seville

  • Hospital Universitari Joan XXIII

    Tarragona

  • Hospital de Terrassa

    Terrassa

  • Hospital Universitari Mútua Terrassa

    Terrassa

  • Hospital Universitario de Torrejon

    Torrejón de Ardoz

  • Hospital Clinico Universitario Lozano Blesa

    Zaragoza

Other trials in Spain

About this study

Official title: Management of Fetal Growth Restriction at Term: Angiogenic Factors Versus Feto-placental Doppler (GRAFD Trial)

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.

Read the detailed description

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).
  1. 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).
Being tested
Management based on sFlt-1/PlGF values
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.

  • Management based on sFlt-1/PlGF valuesProcedure or surgery

    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.
Study groups in NCT04502823
Study groupRoleWhat they receive
Control GroupNo interventionClinical 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 GroupExperimentalManagement based on sFlt-1/PlGF values
Receives: Procedure: Management based on sFlt-1/PlGF values

What is being measured

The primary outcome is the main question the study is designed to answer.

  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)

    Measured: 4-6 weeks

Secondary outcomes (12)

  1. Rate of elective delivery

    Percentage of women that required an elective delivery

    Measured: 4-6 weeks

  2. Rate of Cesarean delivery

    Percentage of women that required a Cesarean delivery

    Measured: 4-6 weeks

  3. Rate of Induction of labor

    Percentage of women that required an induction of labor

    Measured: 4-6 weeks

  4. Rate of neonatal admission in intensive care unit

    Percentage of newborns that required admission in intensive care

    Measured: 4-6 weeks

  5. Time of neonatal admission in intensive care unit

    Days in in intensive care of newborns that required admission

    Measured: 4-6 weeks

  6. Rate of preeclampsia

    Percentage of women that developed preeclampsia

    Measured: 4-6 weeks

  7. Rate of neonatal complications

    Percentage of newborns with adverse outcomes (composite)

    Measured: 4-10 weeks

  8. Rate of maternal complications

    Percentage of women with adverse outcomes (composite)

    Measured: 4-6 weeks

  9. Rate of perinatal complications

    Percentage of perinatal adverse outcomes (composite)

    Measured: 4-6 weeks

  10. Rate of total deliveries at <37, <38, <39 and <40 weeks of gestation

    Percentage of women that delivered at <37, <38, <39 and <40 weeks of gestation

    Measured: 4-6 weeks

  11. Rate of elective deliveries at <37, <38, <39 and <40 weeks of gestation

    Percentage of women that delivered electively at <37, <38, <39 and <40 weeks of gestation

    Measured: 4-6 weeks

  12. Rate of newborns with birthweight <2000 and <2500 grams

    Percentage of women that delivered a newborn with a birthweight <2000 and <2500 grams

    Measured: 4-6 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Aug 2020
  2. Study start21 Sep 2020
  3. Primary completion18 Dec 2022
  4. Study completion18 Dec 2022

Resources

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 N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
1,088 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04502823
Sponsor's protocol ID
PR(AMI)527/2019
Acronym
GRAFD
Status last verified
Jul 2021
First submitted
4 Aug 2020
Last updated
21 Feb 2024
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 39775039

  • 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.

    PubMed 36222789

Questions about this trial

What is this clinical trial studying?

A study testing Management based on sFlt-1/PlGF values in people with Fetal Growth Retardation, run by Hospital Universitari Vall d'Hebron Research Institute at 20 sites in Spain.

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 4 inclusion and 9 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: finished, as of the sponsor's last update on 21 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in Spain. 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.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Adverse perinatal outcomes (time frame: 4-6 weeks). 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 NCT04502823, which also lists 2 linked publications.

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 21 Feb 2024.

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