GRAFD: Management of Fetal Growth Restriction at Term: Angiogenic Factors Versus Feto-placental Doppler
Study Details
Study Description
Brief Summary
Open randomized non-inferiority controlled trial to examine the use of angiogenic factors (instead of feto-placental Doppler) for fetal growth restriction at term to reduce the rate of labor inductions, without worsening perinatal outcomes.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
Pregnant women with estimated fetal weight (EFW) < 10th centile between 36+0 and 37+6 weeks of gestation (WG) will receive complete ultrasonographic assessment consisting of feto-placental Doppler, amniotic fluid measurement and biophysical profile assessment. The cases not meeting any exclusion criteria will be offered to participate in this trial. After giving their informed consent a blood sample will be drawn in all of them and they will undergo randomization into two arms.
- Intervention arm: In women allocated to the intervention group, the soluble fms-like tyrosine kinase/placental growth factor (sFlt-1/PlGF) result will be revealed to the investigators that will act according to the results of sFlt/PlGF:
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Fetuses with sFlt-1/PlGF ≥38, elective delivery will be recommended at ≥37 weeks.
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Fetuses with sFlt-1/PlGF <38, weekly follow up will be recommended until delivery (at ≥40 weeks).
- Control arm: In women allocated to the control group, the sFlt-1/PlGF result will be blinded to caregivers. Routine Doppler-based clinical care will be used to counsel women. Following the Doppler classification:
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Fetuses with EFW below the 3rd centile or below the 10th centile accompanied by any impaired fetoplacental Doppler, elective delivery will be recommended at at ≥37 weeks.
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Fetuses with EFW above the 3rd centile without any fetoplacental Doppler abnormality, elective delivery will be recommended at at ≥40 weeks.
In both arms, fetuses will receive weekly follow-up from randomization to delivery consisting on feto-placental Doppler sFlt-1/PlGF and CTG. If any of the following is present at any time, earlier delivery will be recommended:
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sFlt-1/PlGF ≥38 (only in the intervention group),
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absent or reverse end-diastolic flow at the umbilical artery Doppler or DV PI>95th centile
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non-reassuring CTG
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preeclampsia
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diminished fetal movements
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biophysical profile ≤ 6 or oligohydramnios (deepest pocket <2 cm).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| No Intervention: Control Group Clinical practice: Management by Doppler and CTG findings. In women allocated to the control group, the sFlt-1/PlGF result will be blinded to caregivers. Routine Doppler-based clinical care will be used to counsel women. Following the Doppler classification: Fetuses with an EFW below the 3rd centile or below the 10th centile accompanied by any impaired fetoplacental Doppler, elective delivery will be recommended immediately (within 24h) at ≥37 weeks. Fetuses with an EFW above the 3rd centile without any fetoplacental Doppler abnormality, elective delivery will be recommended at at ≥40 weeks. |
|
| Experimental: Intervention Group Management based on sFlt-1/PlGF values |
Procedure: Management based on sFlt-1/PlGF values
In women allocated to the intervention group, the sFlt-1/PlGF result will be revealed to the investigators that will act according to the results of sFlt/PlGF:
Fetuses with sFlt-1/PlGF ≥38, elective delivery will be recommended immediately (within 24h) at ≥37 weeks.
Fetuses with sFlt-1/PlGF <38 weekly follow up will be recommended and delivery at ≥40 weeks.
|
Outcome Measures
Primary Outcome Measures
- Adverse perinatal outcomes [4-6 weeks]
Cesarean delivery for non-reassuring fetal status or neonatal acidosis (artery cord potential of hydrogen (pH) <7.15 + base excess > -12 milliequivalent/L)
Secondary Outcome Measures
- Rate of elective delivery [4-6 weeks]
Percentage of women that required an elective delivery
- Rate of Cesarean delivery [4-6 weeks]
Percentage of women that required a Cesarean delivery
- Rate of Induction of labor [4-6 weeks]
Percentage of women that required an induction of labor
- Rate of neonatal admission in intensive care unit [4-6 weeks]
Percentage of newborns that required admission in intensive care
- Time of neonatal admission in intensive care unit [4-6 weeks]
Days in in intensive care of newborns that required admission
- Rate of preeclampsia [4-6 weeks]
Percentage of women that developed preeclampsia
- Rate of neonatal complications [4-10 weeks]
Percentage of newborns with adverse outcomes (composite)
- Rate of maternal complications [4-6 weeks]
Percentage of women with adverse outcomes (composite)
- Rate of perinatal complications [4-6 weeks]
Percentage of perinatal adverse outcomes (composite)
- Rate of total deliveries at <37, <38, <39 and <40 weeks of gestation [4-6 weeks]
Percentage of women that delivered at <37, <38, <39 and <40 weeks of gestation
- Rate of elective deliveries at <37, <38, <39 and <40 weeks of gestation [4-6 weeks]
Percentage of women that delivered electively at <37, <38, <39 and <40 weeks of gestation
- Rate of newborns with birthweight <2000 and <2500 grams [4-6 weeks]
Percentage of women that delivered a newborn with a birthweight <2000 and <2500 grams
Eligibility Criteria
Criteria
Inclusion Criteria:
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Pregnant women ≥ 16 years of age.
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Singleton pregnancy.
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Ultrasonographic estimated fetal weight <10th centile.
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Gestational age between 36+0 and 37+6 weeks.
Exclusion Criteria:
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Major fetal malformations or genetic disorders.
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Fetal death.
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Absent or reverse end-diastolic flow in umbilical artery Doppler or DV PI>95th centile.
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Non-reassuring cardiotocography (CTG).
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Preeclampsia.
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Diminished fetal movements.
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Biophysical profile ≤ 6.
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Oligohydramnios
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Refusal to give informed consent.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hospital Universitario de A Coruña | A Coruña | Spain | ||
| 2 | Hospital General de Alicante | Alicante | Spain | ||
| 3 | Hospital Germans Trias i Pujol | Badalona | Spain | ||
| 4 | Hospital Universitari Vall d'hebron | Barcelona | Spain | ||
| 5 | Hospital Universitario de Cabueñes | Cabueñes | Spain | ||
| 6 | Hospital Universitario Puerta del Mar | Cadiz | Spain | ||
| 7 | Hospital General Universitario de Elche | Elche | Spain | ||
| 8 | Hospital Universitario de Getafe | Getafe | Spain | ||
| 9 | Hospital Universitari Doctor Josep Trueta | Girona | Spain | ||
| 10 | Hospital Sant Joan de Deu de Manresa | Manresa | Spain | ||
| 11 | Hospital Clínico Universitario Virgen de la Arrixaca | Murcia | Spain | ||
| 12 | Hospital Son Llàtzer | Palma De Mallorca | Spain | ||
| 13 | Consorci Corporació Sanitària Parc Taulí de Sabadell | Sabadell | Spain | ||
| 14 | Hospital Universitario Nuestra Señora de Candelaria | Santa Cruz De Tenerife | Spain | ||
| 15 | Hospital Universitario Virgen de Valme | Sevilla | Spain | ||
| 16 | Hospital Universitari Joan XXIII | Tarragona | Spain | ||
| 17 | Hospital de Terrassa | Terrassa | Spain | ||
| 18 | Hospital Universitari Mútua Terrassa | Terrassa | Spain | ||
| 19 | Hospital Universitario de Torrejon | Torrejón De Ardoz | Spain | ||
| 20 | Hospital Clinico Universitario Lozano Blesa | Zaragoza | Spain |
Sponsors and Collaborators
- Hospital Universitari Vall d'Hebron Research Institute
Investigators
- Principal Investigator: Manel Mendoza, PhD, Vall d'hebron Institut de Recerca
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PR(AMI)527/2019