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EVERREST Developing a Therapy for Fetal Growth Restriction (EVERREST)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02097667
Recruitment Status : Completed
First Posted : March 27, 2014
Last Update Posted : May 18, 2022
Sponsor:
Collaborators:
University College London Hospitals
Universitätsklinikum Hamburg-Eppendorf
Hospital Clinic of Barcelona
Lund University
Information provided by (Responsible Party):
University College, London

Brief Summary:

Fetal Growth Restriction (FGR) is a major obstetric problem, affecting 1.46 million fetuses worldwide each year and contributing to 50% of stillbirths. Severe early onset FGR affects 1 in 500 pregnancies, leading to stillbirth or the need for delivery before 28 weeks gestation. The combination of FGR and prematurity is associated with a significant risk of neonatal mortality and short and long-term complications. Even modest increases in birthweight (e.g from 500 to 600g) and gestation at delivery (e.g from 26 to 27 weeks) are associated with significantly better outcomes but there are currently no treatments.

The EVERREST Clinical Trial, funded by the European Commission, aims to develop a treatment which will increase fetal growth in severe early onset FGR. It will use gene therapy injected into the uterine arteries of the mother to increase the levels of vascular endothelial growth factor (VEGF) and so increase uterine artery blood flow and fetal growth.

The EVERREST prospective study aims to form a clinical database and biobank of pregnancies affected by severe early onset FGR to improve understanding of the condition and serve as a comparison to assess the safety and efficacy of this intervention.

The prospective study will take place across four European centers who will later take part in the EVERREST Clinical Trial. Women with singleton fetuses with early onset FGR will be approached to take part in the study. Participating women will provide blood samples, details of their clinical condition, samples of umbilical cord blood, placenta and myometrial and placental bed biopsies at the time of Caesarean section (if needed). Data on short and long-term outcomes of the babies will be collected. All data will be entered onto a central database for eventual use as a comparator for treated women on the EVERREST Clinical Trial, for which separate ethical approval will be sought.


Condition or disease
Fetal Growth Retardation

Show Show detailed description

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Study Type : Observational
Actual Enrollment : 142 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: EVERREST - Developing a Therapy for Fetal Growth Restriction. A 6 Year Prospective Study to Define the Clinical and Biological Characteristic of Pregnancies Affected by Severe Early Onset Fetal Growth Restriction.
Actual Study Start Date : March 2014
Actual Primary Completion Date : February 2022
Actual Study Completion Date : February 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pregnancy




Primary Outcome Measures :
  1. data collection from pregnancies affected by severe early onset FGR. [ Time Frame: each hospital visit and up to 2 years follow up for babies ]

    As the study will be purely descriptive there are no defined primary outcome measures. Data will be collected on the following:

    • Parental demographics
    • Maternal past medical history and obstetric history
    • Antenatal ultrasound findings including growth and Doppler measurements
    • Maternal antenatal, perinatal and postnatal complications and treatment
    • Stillbirth
    • Delivery and immediate neonatal condition
    • Neonatal progress including complications, treatment and neonatal death
    • Infant growth and development up to 2 years corrected age
    • Maternal and neonatal service use


Other Outcome Measures:
  1. Model validation 1 [ Time Frame: 2021 ]

    The following models, developed in a discovery set of n=63, will be validated in the remaining participants. Model parameters are transformed values of maternal serum protein concentrations or normalised protein expression. Model estimates (area under the curve (AUC) and 95% confidence intervals (95%CI)) are from leave-one-out cross-validation for outcomes 1 and 2 and from 5-fold cross-validation with bootstrap bias CI correction for outcome 3.

    Outcome 1: fetal or neonatal death

    1. Placental growth factor (PlGF): AUC 0.749 (95%CI 0.615-0.883)
    2. PlGF & lymphotactin: AUC 0.839 (0.731-0.947)
    3. PlGF, lymphotactin & fibronectin: AUC 0.848 (0.735-0.961)

  2. Model validation 2 [ Time Frame: 2021 ]

    Outcome 2: Fetal death or delivery <28+0 weeks of gestation

    1. PlGF: AUC 0.858 (0.760-0.956)
    2. PlGF & pregnancy specific beta-1 glycoprotein 1 (PSG1): AUC 0.906 (0.818-0.994)

    Outcome 3: Development of umbilical artery pulsatility index (UmAPI) >95th centile (Schaffer & Stauch) in pregnancies with UmAPI <95th centile at enrolment

    1. PlGF: AUC 0.844 (0.495-0.950)
    2. PlGF & fibronectin: AUC 0.900 (0.620-0.991)


Biospecimen Retention:   Samples With DNA
Plasma, serum, whole blood, fixed placenta, frozen placenta, fixed placenta bed.


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Pregnant women with FGR
Criteria

Inclusion Criteria:

  • Live singleton fetus
  • Estimated fetal weight <600g and <3rd centile for gestational age as defined by local criteria
  • Gestational age at diagnosis 20+0-26+6 weeks, based on ultrasound and/or last menstrual period
  • Informed consent given by the participant and signed consent form completed

Exclusion Criteria:

  • Multiple pregnancy
  • Maternal age under 18 years
  • Known abnormal karyotype at enrolment
  • Known structural abnormality at enrolment defined as a lethal, incurable serve abnormality with a high risk of residual handicap.
  • Indication for immediate delivery
  • Participants who lack the capacity to give informed consent
  • Any medical or psychiatric condition which compromises the participant's ability to participate
  • Maternal HIV or hepatitis B or C infection
  • Premature preterm rupture of membranes before enrolment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02097667


Locations
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Germany
University Medical Center Hamburg-Eppendorf
Hamburg, Germany
Spain
Maternal-Fetal Unit Hospital Clinic de Barcelona
Barcelona, Spain
Sweden
Lund University Hospital and University Hospital Malmö
Malmo, Sweden
United Kingdom
University College London Hospital
London, United Kingdom
Sponsors and Collaborators
University College, London
University College London Hospitals
Universitätsklinikum Hamburg-Eppendorf
Hospital Clinic of Barcelona
Lund University
Investigators
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Principal Investigator: Anna David, Dr Institute of Women's Health, UCL
Publications:
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Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT02097667    
Other Study ID Numbers: 13/0289
First Posted: March 27, 2014    Key Record Dates
Last Update Posted: May 18, 2022
Last Verified: May 2022
Keywords provided by University College, London:
Severe early onset Fetal Growth Restriction
Additional relevant MeSH terms:
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Fetal Growth Retardation
Fetal Diseases
Pregnancy Complications
Growth Disorders
Pathologic Processes