Management of Early-onset Fetal Growth Restriction: Angiogenic Factors Versus Feto-placental Doppler (earlyGRAFD)

Vall d'Hebron University Hospital (HUVH)

Status: Not yet enrolling

Conditions: Fetal Growth Retardation; Preeclampsia; Placenta Diseases

Treatments: Diagnostic Test: soluble fms-like tyrosine kinase to placental growth factor ratio (sFlt-1/PlGF)

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05284474

PR(AMI)113/2022

Details and patient eligibility

About

This is a multicentre, open-label, randomized controlled trial. A total of 340 singleton pregnancies with an EFW ≤10th percentile between 26+0 and 31+6 weeks will be recruited and randomly allocated to either the control or the intervention group. In the control group, standard Doppler-based management will be used. In the intervention group, different soluble fms-like tyrosine kinase to placental growth factor ratio (sFlt-1/PlGF) cutoffs will be incorporated to the current protocol to adjust the frequency of ultrasounds and to plan elective delivery.

Enrollment: 340 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Pregnant women of at least 18 years old
• Singleton pregnancy
• Ultrasonographic EFW ≤10th percentile between 26+0 and 31+6 weeks of gestation
• Gestational age confirmed by fetal crown-rump length measurement during the first trimester scan (from 11+0 to 13+6 weeks of gestation) or by in vitro fertilization dates.

Exclusion criteria

• Major fetal malformations or genetic disorders
• Fetal death
• Refusal to give informed consent
• Stage IV FGR

Trial design

Primary purpose: Diagnostic

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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340 participants in 2 patient groups

Control

No Intervention group

Description:

Small fetuses will be classified into 5 severity stages and managed as follows: * SGA: Estimated fetal weight (EFW) between p3 and p10 with normal Dopplers. Ultrasound/2 weeks, elective vaginal delivery at ≥39-40 weeks. * Stage I: EFW ≤p3 p or EFW p3-10 + UA PI \>p95 and/or UtA PI \>p95, and, at ≥32 weeks, CPR and/or MCA PI \<p5, in 2 occasions \>12 hours apart. Ultrasound weekly, elective vaginal delivery at ≥37 weeks. * Stage II: AEDF UA in 2 occasions \>12 hours apart. Ultrasound every 48-72h, elective Cesarean delivery at ≥34 weeks. * Stage III: DV PI \> p95 (or absent DV "a" wave) or reversed end-diastolic UA \>50% of cycles, in both cases in two occasions \> 6 hours apart. Ultrasound every 24-48h, elective Cesarean delivery at ≥30 weeks. * Stage IV: reversed DV "a" wave in two occasions \> 6 hours apart. Elective Cesarean delivery at ≥26 weeks.

Study

Experimental group

Description:

Doppler protocol (as in controls) + sFlt-1/PlGF ratio cutoffs will be incorporated as follows: * \<38: Ultrasound biweekly in stage I FGR and every four weeks in SGA. In both cases delivery at ≥39-40 weeks. * 38-110: In stage I FGR and SGA ultrasound weekly. Delivery at ≥37 weeks. * \>110: In stage I FGR and SGA ultrasound weekly. Delivery at ≥36 weeks. * \>110 and concurrent preeclampsia: In stage I FGR and SGA ultrasound every 48h-72h. Delivery at ≥34 weeks. * \>201: Ultrasound every 48-72h, delivery at ≥34+0 weeks. If concurrent preeclampsia, delivery at ≥32+0 weeks. * \>655: Ultrasound every 48-72h, delivery at ≥32+0 weeks. If concurrent preeclampsia, delivery at ≥30+0 weeks. * \>1000: In cases with concurrent PE, delivery at ≥29+0 weeks.

Treatment:

Diagnostic Test: soluble fms-like tyrosine kinase to placental growth factor ratio (sFlt-1/PlGF)