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

NCT05284474 | Not Yet Recruiting

• 1 other identifier: PR(AMI)113/2022
• Study Type: interventional
• Target: 340
• Locations: 1 country
• Sites: 27

Brief Summary

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.

Conditions

Fetal Growth Retardation; Preeclampsia; Placenta Diseases

Keywords

fetal growth restriction; small for gestational age; PlGF; sFlt-1; Doppler

Outcome Measures

Primary Outcomes (2)

• Fetal and Neonatal complications

  stillbirth, neonatal death, artery cord pH ≤7.0, respiratory distress syndrome, required invasive ventilatory support, grade III or IV intraventricular hemorrhage, neonatal sepsis, necrotizing enterocolitis, neonatal seizures, pneumonia, meningitis, broncopulmonary dysplasia, hypoxic ischemic encephalopathy, Apgar score \<7 at 5 minutes, or elective delivery at \<28 weeks of gestation.

  During pregnancy and up to 28 days after delivery

• Composite adverse maternal outcome

  Progression to PE with severity features; progression to hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome (LDH \>600 IU/L, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) elevated more than twice the upper limit of normal, and the platelet count less than 100 X 109/L); eclampsia, stroke, hepatic hematoma or rupture; oliguria (urine output of \<400 mL during 24 hours, or need for treatment with furosemide to maintain urine output at \>400 mL for 24 hours); cardiovascular dysfunction (need for inotropic support, left ventricle failure, or myocardial infarction); placental abruption; maternal death; maternal admission to intensive care unit \>48 hours, and/or requirement for blood transfusion.

  During pregnancy and up to 28 days after delivery

Secondary Outcomes (3)

• Maternal perceived stress

  At inclusion and 4 weeks later

• Other perinatal outcomes

  During pregnancy and up to 28 days after delivery

• Number of ultrasounds per participant

  During pregnancy (before and after 37 weeks)

Study Arms (2)

Control

NO INTERVENTION

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

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.

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

Interventions

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

soluble fms-like tyrosine kinase to placental growth factor ratio (sFlt-1/PlGF) will be incorporated to the management of early-onset small fetuses (estimated fetal weight ≤10th percentile)

Study

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: pregnant women
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Hospital Universitari Vall d'Hebron Research Institute: lead
• Instituto de Salud Carlos III: collaborator
• Roche Diagnostics GmbH: collaborator

Study Sites (27)

Complejo Hospitalario Universitario de A Coruña

A Coruña, Spain

Location

Hospital Universitario General de Alicante

Alicante, Spain

Location

Hospital Universitari Germans Trias i Pujol

Badalona, Spain

Location

Vall d'hebron Barcelona Hospital Campus

Barcelona, 08035, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain

Location

Hospital Universitari Dexeus

Barcelona, 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 Universitario de Cabueñes

Gijón, Spain

Location

Hospital Universitari de Girona Doctor Josep Trueta

Girona, Spain

Location

Hospital Universitario San Cecilio

Granada, Spain

Location

Hospital Universitario de Jerez de la Frontera

Jerez de la Frontera, Spain

Location

Hospital Materno Infantil de Gran Canaria

Las Palmas de Gran Canaria, Spain

Location

Hospital Universitari Arnau de Vilanova

Lleida, Spain

Location

Hospital Clínico San Carlos

Madrid, Spain

Location

Hospital Universitari Son Espases

Palma de Mallorca, Spain

Location

Hospital Universitari Son Llàtzer

Palma de Mallorca, Spain

Location

Corporació Sanitària Parc Taulí

Sabadell, Spain

Location

Hospital Universitario de Canarias

Santa Cruz de Tenerife, Spain

Location

Hospital Universitario Virgen de Valme

Seville, Spain

Location

Virgen Macarena

Seville, Spain

Location

Hospital Universitario Joan XXIII de Tarragona

Tarragona, Spain

Location

Consorci Sanitari de Terrassa

Terrassa, Spain

Location

Hospital Universitari Mútua Terrassa

Terrassa, Spain

Location

Hospital Universitario de Torrejón

Torrejón de Ardoz, Spain

Location

Hospital Clínico Universitario Lozano Blesa

Zaragoza, Spain

Location

MeSH Terms

Conditions

Fetal Growth Retardation; Pre-Eclampsia; Placenta Diseases

Condition Hierarchy (Ancestors)

Fetal Diseases; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Growth Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hypertension, Pregnancy-Induced

Study Officials

• Manel Mendoza, MD, PhD

  Vall d'Hebron Institut de Recerca (VHIR)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Manel Mendoza, MD, PhD

CONTACT

+34934893000; manel.mendoza@vallhebron.cat

Study Design

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

Study Record Dates

• First Submitted: February 13, 2022
• First Posted: March 17, 2022
• Study Start: June 3, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: June 4, 2024

Record last verified: 2024-05

Locations

ES (27)