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

Fetal Growth Retardation Clinical Trial

— GRAFD  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04502823
• Other study ID #: PR(AMI)527/2019
• Status: Completed
• Phase: N/A
• Start date: September 21, 2020
• Est. completion date: December 18, 2022

Study information

• Verified date: July 2021
• Source: Hospital Universitari Vall d'Hebron Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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 information / eligibility

• Status: Completed
• Enrollment: 1088
• Est. completion date: December 18, 2022
• Est. primary completion date: December 18, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 16 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Fetal Growth Retardation

Intervention

Procedure:
• 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.

Locations

Country	Name	City	State
Spain	Hospital Universitario de A Coruña	A Coruña
Spain	Hospital General de Alicante	Alicante
Spain	Hospital Germans Trias i Pujol	Badalona
Spain	Hospital Universitari Vall d'hebron	Barcelona
Spain	Hospital Universitario de Cabueñes	Cabueñes
Spain	Hospital Universitario Puerta del Mar	Cadiz
Spain	Hospital General Universitario de Elche	Elche
Spain	Hospital Universitario de Getafe	Getafe
Spain	Hospital Universitari Doctor Josep Trueta	Girona
Spain	Hospital Sant Joan de Deu de Manresa	Manresa
Spain	Hospital Clínico Universitario Virgen de la Arrixaca	Murcia
Spain	Hospital Son Llàtzer	Palma De Mallorca
Spain	Consorci Corporació Sanitària Parc Taulí de Sabadell	Sabadell
Spain	Hospital Universitario Nuestra Señora de Candelaria	Santa Cruz De Tenerife
Spain	Hospital Universitario Virgen de Valme	Sevilla
Spain	Hospital Universitari Joan XXIII	Tarragona
Spain	Hospital de Terrassa	Terrassa
Spain	Hospital Universitari Mútua Terrassa	Terrassa
Spain	Hospital Universitario de Torrejon	Torrejón De Ardoz
Spain	Hospital Clinico Universitario Lozano Blesa	Zaragoza

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Universitari Vall d'Hebron Research Institute

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Rate of elective delivery	Percentage of women that required an elective delivery	4-6 weeks
Secondary	Rate of Cesarean delivery	Percentage of women that required a Cesarean delivery	4-6 weeks
Secondary	Rate of Induction of labor	Percentage of women that required an induction of labor	4-6 weeks
Secondary	Rate of neonatal admission in intensive care unit	Percentage of newborns that required admission in intensive care	4-6 weeks
Secondary	Time of neonatal admission in intensive care unit	Days in in intensive care of newborns that required admission	4-6 weeks
Secondary	Rate of preeclampsia	Percentage of women that developed preeclampsia	4-6 weeks
Secondary	Rate of neonatal complications	Percentage of newborns with adverse outcomes (composite)	4-10 weeks
Secondary	Rate of maternal complications	Percentage of women with adverse outcomes (composite)	4-6 weeks
Secondary	Rate of perinatal complications	Percentage of perinatal adverse outcomes (composite)	4-6 weeks
Secondary	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	4-6 weeks
Secondary	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	4-6 weeks
Secondary	Rate of newborns with birthweight <2000 and <2500 grams	Percentage of women that delivered a newborn with a birthweight <2000 and <2500 grams	4-6 weeks