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

June 3, 2024 updated by: Hospital Universitari Vall d'Hebron Research Institute

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
340

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
No Intervention: Control

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.
Experimental: Study

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)
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)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Fetal and Neonatal complications
Time Frame: During pregnancy and up to 28 days after delivery
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
Time Frame: During pregnancy and up to 28 days after delivery
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Maternal perceived stress
Time Frame: At inclusion and 4 weeks later
Mean and sd or median and IQR of the score obtained in the perceived stress scale in each group
At inclusion and 4 weeks later
Other perinatal outcomes
Time Frame: During pregnancy and up to 28 days after delivery
transient tachypnea, non-invasive ventilatory support, hypoglycemia, neonatal jaundice (treated with phototherapy), rate of elective deliveries < 30 weeks, <34 weeks and < 37 weeks for FGR and/or PE, birthweight <3 rd and <10th percentiles, mode of delivery (vaginal, instrumental vaginal delivery and Cesarean), rate of Cesarean delivery for abnormal CTG, median maternal stay in ICU, median neonatal stay in N-ICU, maternal corticosteroids (single dose, complete course), prenatal magnesium sulfate (at least 4h) for preterm delivery.
During pregnancy and up to 28 days after delivery
Number of ultrasounds per participant
Time Frame: During pregnancy (before and after 37 weeks)
Mean and sd or median and IQR in each group
During pregnancy (before and after 37 weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hospital Universitari Vall d'Hebron Research Institute

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Instituto de Salud Carlos III
Roche Diagnostics GmbH

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Manel Mendoza, MD, PhD, Vall d'Hebron Institut de Recerca (VHIR)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 3, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 30, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 13, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 9, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 17, 2022

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 4, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 3, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PR(AMI)113/2022

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings