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

Not Applicable
Completed
Conditions
Fetal Growth Retardation
Interventions
Procedure: Management based on sFlt-1/PlGF values
Registration Number
NCT04502823
Lead Sponsor
Hospital Universitari Vall d'Hebron Research Institute
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.

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).

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).

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
1088
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Intervention GroupManagement based on sFlt-1/PlGF valuesManagement based on sFlt-1/PlGF values
Primary Outcome Measures
NameTimeMethod
Adverse perinatal outcomes4-6 weeks

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

Secondary Outcome Measures
NameTimeMethod
Rate of Cesarean delivery4-6 weeks

Percentage of women that required a Cesarean delivery

Rate of total deliveries at <37, <38, <39 and <40 weeks of gestation4-6 weeks

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

Rate of maternal complications4-6 weeks

Percentage of women with adverse outcomes (composite)

Rate of Induction of labor4-6 weeks

Percentage of women that required an induction of labor

Rate of neonatal complications4-10 weeks

Percentage of newborns with adverse outcomes (composite)

Rate of elective delivery4-6 weeks

Percentage of women that required an elective delivery

Time of neonatal admission in intensive care unit4-6 weeks

Days in in intensive care of newborns that required admission

Rate of preeclampsia4-6 weeks

Percentage of women that developed preeclampsia

Rate of neonatal admission in intensive care unit4-6 weeks

Percentage of newborns that required admission in intensive care

Rate of perinatal complications4-6 weeks

Percentage of perinatal adverse outcomes (composite)

Rate of elective deliveries at <37, <38, <39 and <40 weeks of gestation4-6 weeks

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

Rate of newborns with birthweight <2000 and <2500 grams4-6 weeks

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

Trial Locations

Locations (20)

Hospital Clinico Universitario Lozano Blesa

🇪🇸

Zaragoza, Spain

Hospital Universitario de A Coruña

🇪🇸

A Coruña, Spain

Hospital Universitari Mútua Terrassa

🇪🇸

Terrassa, Spain

Hospital Universitario de Torrejon

🇪🇸

Torrejón De Ardoz, Spain

Hospital de Terrassa

🇪🇸

Terrassa, Spain

Hospital Germans Trias i Pujol

🇪🇸

Badalona, Spain

Hospital Universitario Virgen de Valme

🇪🇸

Sevilla, Spain

Consorci Corporació Sanitària Parc Taulí de Sabadell

🇪🇸

Sabadell, Spain

Hospital Son Llàtzer

🇪🇸

Palma De Mallorca, Spain

Hospital Clínico Universitario Virgen de la Arrixaca

🇪🇸

Murcia, Spain

Hospital Universitario Nuestra Señora de Candelaria

🇪🇸

Santa Cruz De Tenerife, Spain

Hospital Universitari Joan XXIII

🇪🇸

Tarragona, Spain

Hospital Universitario de Cabueñes

🇪🇸

Cabueñes, Spain

Hospital Universitario Puerta del Mar

🇪🇸

Cadiz, Spain

Hospital General de Alicante

🇪🇸

Alicante, Spain

Hospital General Universitario de Elche

🇪🇸

Elche, Spain

Hospital Universitario de Getafe

🇪🇸

Getafe, Spain

Hospital Universitari Vall d'hebron

🇪🇸

Barcelona, Spain

Hospital Sant Joan de Deu de Manresa

🇪🇸

Manresa, Spain

Hospital Universitari Doctor Josep Trueta

🇪🇸

Girona, Spain

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