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

Primary Purpose

Fetal Growth Retardation, Preeclampsia, Placenta Diseases

Status
Not yet recruiting
Phase
Not Applicable
Locations
Spain
Study Type
Interventional
Intervention
soluble fms-like tyrosine kinase to placental growth factor ratio (sFlt-1/PlGF)
Sponsored by
Hospital Universitari Vall d'Hebron Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Fetal Growth Retardation focused on measuring fetal growth restriction, small for gestational age, PlGF, sFlt-1, Doppler

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Pregnant women of at least 18 years old
  • Singleton pregnancy
  • Ultrasonographic EFW ≤10th percentile between 24+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

Sites / Locations

  • Complejo Hospitalario Universitario de A Coruña
  • Hospital Universitario General de Alicante
  • Hospital Universitari Germans Trias i Pujol
  • Vall d'hebron Barcelona Hospital Campus
  • Hospital de la Santa Creu i Sant Pau
  • Hospital Universitari Dexeus
  • Hospital Universitario Puerta del Mar
  • Hospital General Universitario de Elche
  • Hospital Universitario de Getafe
  • Hospital Universitario de Cabueñes
  • Hospital Universitari de Girona Doctor Josep Trueta
  • Hospital Universitario San Cecilio
  • Hospital Universitario de Jerez de la Frontera
  • Hospital Universitari Arnau de Vilanova
  • Hospital Universitari Son Espases
  • Hospital Universitari Son Llàtzer
  • Corporació Sanitària Parc Taulí
  • Hospital Universitario de Canarias
  • Hospital Universitario Virgen de Valme
  • Hospital Universitario Joan XXIII de Tarragona
  • Consorci Sanitari de Terrassa
  • Hospital Universitari Mútua Terrassa
  • Hospital Universitario de Torrejón
  • Hospital Clínico Universitario Lozano Blesa

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Experimental

Arm Label

Control

Study

Arm 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. Fetal lung maturation at ≥ 33 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. Fetal lung maturation at ≥ 28 weeks. Stage IV: reversed DV "a" wave in two occasions > 6 hours apart. Elective Cesarean delivery at ≥26 weeks. Fetal lung maturation at ≥ 25+5 weeks.

Doppler protocol (as in controls) + sFlt-1/PlGF ratio cutoffs will be incorporated as follows: <38: Ultrasound biweekly in stage I FGR and every three weeks in SGA. In both cases delivery at ≥39-40 weeks. 38-85: In stage I FGR and SGA ultrasound weekly. Delivery at ≥37 weeks. >85: In stage I FGR and SGA ultrasound every 72h-96h. Delivery at ≥37 weeks. >110: In stage I FGR and SGA ultrasound every 48h-72h. Delivery at ≥36 weeks. If concurrent preeclampsia, delivery at ≥34+0 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 ≥28+0 weeks.

Outcomes

Primary Outcome Measures

Rate of severe perinatal complications
Preeclampsia with severity features, placental abruption, eclampsia, stillbirth, neonatal death, umbilical artery pH ≤7.0
Composite adverse maternal outcome
Percentage of pregnancies with HELLP syndrome, severe PE, eclampsia, stroke, hepatic hematoma or rupture, oliguria, need for furosemide, cardiovascular dysfunction (inotropic support, myocardial infarction, left ventricle failure), placental abruption, maternal admission to intensive care unit >48h, and/or requirement for blood transfusion in each group.
Number of ultrasounds per participant
Mean and sd or median and IQR in each group
Rate of elective deliveries <30 weeks
Percentage of deliveries indicated for FGR and/or PE <30 weeks
Rate of elective deliveries <34 weeks
Percentage of deliveries indicated for FGR and/or PE <34 weeks

Secondary Outcome Measures

Maternal perceived stress
Mean and sd or median and IQR of the score obtained in the perceived stress scale in each group
Rate of elective deliveries <37 weeks
Percentage of deliveries indicated for FGR and/or PE <37 weeks
Composite adverse neonatal outcome
Percentage of neonates with Apgar score <7, umbilical artery pH ≤7.0, respiratory distress syndrome, transient tachypnea, required ventilatory support, grade III or IV intraventricular hemorrhage, neonatal sepsis, hypoglucemia, necrotizing enterocolitis, neonatal jaundice treated with phototherapy, neonatal seizures, pneumonia, meningitis and/or neonatal death.

Full Information

First Posted
February 13, 2022
Last Updated
March 17, 2022
Sponsor
Hospital Universitari Vall d'Hebron Research Institute
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1. Study Identification

Unique Protocol Identification Number
NCT05284474
Brief Title
Management of Early-onset Fetal Growth Restriction: Angiogenic Factors Versus Feto-placental Doppler
Acronym
earlyGRAFD
Official Title
Management of Early-onset Fetal Growth Restriction: Angiogenic Factors Versus Feto-placental Doppler (Early GRAFD)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
September 1, 2022 (Anticipated)
Primary Completion Date
September 1, 2024 (Anticipated)
Study Completion Date
January 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospital Universitari Vall d'Hebron Research Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
This is a multicentre, open-label, randomized controlled trial. A total of 598 singleton pregnancies with an EFW ≤10th percentile at <32+0 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fetal Growth Retardation, Preeclampsia, Placenta Diseases
Keywords
fetal growth restriction, small for gestational age, PlGF, sFlt-1, Doppler

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
598 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Control
Arm Type
No Intervention
Arm 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. Fetal lung maturation at ≥ 33 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. Fetal lung maturation at ≥ 28 weeks. Stage IV: reversed DV "a" wave in two occasions > 6 hours apart. Elective Cesarean delivery at ≥26 weeks. Fetal lung maturation at ≥ 25+5 weeks.
Arm Title
Study
Arm Type
Experimental
Arm 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 three weeks in SGA. In both cases delivery at ≥39-40 weeks. 38-85: In stage I FGR and SGA ultrasound weekly. Delivery at ≥37 weeks. >85: In stage I FGR and SGA ultrasound every 72h-96h. Delivery at ≥37 weeks. >110: In stage I FGR and SGA ultrasound every 48h-72h. Delivery at ≥36 weeks. If concurrent preeclampsia, delivery at ≥34+0 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 ≥28+0 weeks.
Intervention Type
Diagnostic Test
Intervention Name(s)
soluble fms-like tyrosine kinase to placental growth factor ratio (sFlt-1/PlGF)
Intervention Description
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)
Primary Outcome Measure Information:
Title
Rate of severe perinatal complications
Description
Preeclampsia with severity features, placental abruption, eclampsia, stillbirth, neonatal death, umbilical artery pH ≤7.0
Time Frame
During pregnancy and up to 28 days after delivery
Title
Composite adverse maternal outcome
Description
Percentage of pregnancies with HELLP syndrome, severe PE, eclampsia, stroke, hepatic hematoma or rupture, oliguria, need for furosemide, cardiovascular dysfunction (inotropic support, myocardial infarction, left ventricle failure), placental abruption, maternal admission to intensive care unit >48h, and/or requirement for blood transfusion in each group.
Time Frame
During pregnancy and up to 28 days after delivery
Title
Number of ultrasounds per participant
Description
Mean and sd or median and IQR in each group
Time Frame
During pregnancy
Title
Rate of elective deliveries <30 weeks
Description
Percentage of deliveries indicated for FGR and/or PE <30 weeks
Time Frame
During pregnancy
Title
Rate of elective deliveries <34 weeks
Description
Percentage of deliveries indicated for FGR and/or PE <34 weeks
Time Frame
During pregnancy
Secondary Outcome Measure Information:
Title
Maternal perceived stress
Description
Mean and sd or median and IQR of the score obtained in the perceived stress scale in each group
Time Frame
During pregnancy
Title
Rate of elective deliveries <37 weeks
Description
Percentage of deliveries indicated for FGR and/or PE <37 weeks
Time Frame
During pregnancy
Title
Composite adverse neonatal outcome
Description
Percentage of neonates with Apgar score <7, umbilical artery pH ≤7.0, respiratory distress syndrome, transient tachypnea, required ventilatory support, grade III or IV intraventricular hemorrhage, neonatal sepsis, hypoglucemia, necrotizing enterocolitis, neonatal jaundice treated with phototherapy, neonatal seizures, pneumonia, meningitis and/or neonatal death.
Time Frame
During pregnancy and up to 28 days after delivery

10. Eligibility

Sex
Female
Gender Based
Yes
Gender Eligibility Description
pregnant women
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Pregnant women of at least 18 years old Singleton pregnancy Ultrasonographic EFW ≤10th percentile between 24+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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Manel Mendoza, MD, PhD
Phone
+34934893000
Ext
3085
Email
mmendoza@vhebron.net
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Manel Mendoza, MD, PhD
Organizational Affiliation
Vall d'Hebron Institut de Recerca (VHIR)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Complejo Hospitalario Universitario de A Coruña
City
A Coruña
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nuria Valiño
Email
nuvalino@gmail.com
Facility Name
Hospital Universitario General de Alicante
City
Alicante
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ana Palacios
Email
ana.palacios.marques@gmail.com
Facility Name
Hospital Universitari Germans Trias i Pujol
City
Badalona
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ivan Hurtado
Email
ivan.hurtado85@gmail.com
Facility Name
Vall d'hebron Barcelona Hospital Campus
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Manel Mendoza, MD, PhD
Phone
934893000
Ext
3085
Email
mmendoza@vhebron.net
Facility Name
Hospital de la Santa Creu i Sant Pau
City
Barcelona
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cristina Trilla
Email
ctrilla@santpau.cat
Facility Name
Hospital Universitari Dexeus
City
Barcelona
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pilar Prats
Email
pilpra@dexeus.com
Facility Name
Hospital Universitario Puerta del Mar
City
Cadiz
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maria Angeles Anaya
Email
manaya2404@gmail.com
Facility Name
Hospital General Universitario de Elche
City
Elche
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elena Moreno
Email
elenamorenoperez@hotmail.com
Facility Name
Hospital Universitario de Getafe
City
Getafe
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elena Pintado
Email
elenapintadoparedes@gmail.com
Facility Name
Hospital Universitario de Cabueñes
City
Gijón
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Esther Perez
Email
estherpcarbajo@hotmail.com
Facility Name
Hospital Universitari de Girona Doctor Josep Trueta
City
Girona
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alexandra Bonmatí
Email
abonmatis.girona.ics@gencat.cat
Facility Name
Hospital Universitario San Cecilio
City
Granada
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maria del Carmen Jimenez
Email
mcarmenjimenezhernandez@gmail.com
Facility Name
Hospital Universitario de Jerez de la Frontera
City
Jerez De La Frontera
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cristina Romero
Email
CRGARRI@GMAIL.COM
Facility Name
Hospital Universitari Arnau de Vilanova
City
Lleida
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Emilio Maestre
Email
emaestremir@gmail.com
Facility Name
Hospital Universitari Son Espases
City
Palma De Mallorca
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maria Vila
Email
mariavilacortes@gmail.com
Facility Name
Hospital Universitari Son Llàtzer
City
Palma De Mallorca
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Beatriz Soriano
Email
bea180680@gmail.com
Facility Name
Corporació Sanitària Parc Taulí
City
Sabadell
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anna Moreno
Email
annmorenoba@gmail.com
Facility Name
Hospital Universitario de Canarias
City
Santa Cruz De Tenerife
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Merecedes Hernandez
Email
mercedes021281@hotmail.com
Facility Name
Hospital Universitario Virgen de Valme
City
Sevilla
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carlota Borrero
Email
carlotaborrero@gmail.com
Facility Name
Hospital Universitario Joan XXIII de Tarragona
City
Tarragona
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Monica Lopez
Email
monicalopez4099@gmail.com
Facility Name
Consorci Sanitari de Terrassa
City
Terrassa
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Angels Vives
Email
vivesangels@gmail.com
Facility Name
Hospital Universitari Mútua Terrassa
City
Terrassa
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eva Lopez
Email
evalq@hotmail.com
Facility Name
Hospital Universitario de Torrejón
City
Torrejón De Ardoz
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Raquel Martin, MD
Email
raqmaral@gmail.com
Facility Name
Hospital Clínico Universitario Lozano Blesa
City
Zaragoza
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Patricia Ibañez
Email
patribanez@hotmail.com

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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