Randomizated Open-label Control Trial to Evaluate if the Incorporation of sFlt1/PlGF Ratio in the Diagnosis and Classification of PE Improves Maternal and Perinatal Outcomes in Women With the Suspicion of the Disease (EuroPE)
Primary Purpose
Preeclampsia
Status
Recruiting
Phase
Not Applicable
Locations
Spain
Study Type
Interventional
Intervention
Placental biomarkers
Sponsored by
About this trial
This is an interventional diagnostic trial for Preeclampsia focused on measuring preeclampsia, intrauterine growth restriction, angiogenic factors
Eligibility Criteria
Inclusion Criteria:
- Ability to read and understand informed consent.
- Unique pregnancies.
- > 24 weeks and <41 weeks
Suspected preeclampsia:
- 140/90 or worsening of chronic hypertension
- Onset of proteinuria (Labstick + or proteinuria> 300mg / 24 hours) or worsening of it
- Preeclampsia prodromal clinic such as epigastric, headache, photopsia, tinnitus and increased edema in the face hands or legs or weight gain (> 1 kg per week in the third trimester)
- Analytical alterations: decrease in platelets <100,000. Increased transaminases.
- Ultrasound alterations: Small fetus for gestational age or restriction of interatrial growth, increased resistance of the uterine arteries.
- Pre-eclampsia (ACOG Practice Bulletin 2013)
Exclusion Criteria:
- Multiple pregnancies
- <24 weeks of gestation
- Fetal chromosomal or congenital abnormalities
- Conditions that require immediate delivery (eclampsia, pulmonary edema, uncontrolled hypertension, severe visual disturbances, severe headache, fetal demise, non-reassuring fetal status….)
Sites / Locations
- Hospital de la Santa Creu i Sant PauRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Incorporation of the sFlt1/P1GF ratio
Routine clinical practice
Arm Description
Incorporation of the ratio in the diagnosis and classification of pre-eclampsia: sFlt1/PlGF ratio >38: pre-eclampsia risk sFlt1/PlGF ratio >85: pre-eclampsia ISSHP pre-eclampsia definition + ratio >210: severe PE ISSHP pre-eclampsia definition + ratio sFlt1/PlGF ratio >600: consider deliver
Criteria for the definition of PE were those of the International Society for the Study of Hypertension in Pregnancy
Outcomes
Primary Outcome Measures
Adverse outcomes
Composite score for adverse outcomes defined as the presence of any of the following: premature placental abruption, cessation of abnormal CTG, fetal death, need for 2 or more antihypertensive drugs, eclampsia, disseminated intravascular coagulation, maternal mortality, postpartum haemorrhage (need for more than 2 concentrated hematies), acute pulmonary edema, cerebral vascular hemorrhage, pulmonary embolism, sepsis, ICU admission, need for second surgery.
Secondary Outcome Measures
Full Information
NCT ID
NCT03231657
First Posted
July 24, 2017
Last Updated
August 10, 2022
Sponsor
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Collaborators
Carlos III Health Institute, Spanish Clinical Research Network - SCReN
1. Study Identification
Unique Protocol Identification Number
NCT03231657
Brief Title
Randomizated Open-label Control Trial to Evaluate if the Incorporation of sFlt1/PlGF Ratio in the Diagnosis and Classification of PE Improves Maternal and Perinatal Outcomes in Women With the Suspicion of the Disease
Acronym
EuroPE
Official Title
Randomizated Open-label Control Trial to Evaluate if the Incorporation of sFlt1/PlGF Ratio in the Diagnosis and Classification of PE Improves Maternal and Perinatal Outcomes in Women With the Suspicion of the Disease (EuroPE Study)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Recruiting
Study Start Date
February 6, 2018 (Actual)
Primary Completion Date
December 2022 (Anticipated)
Study Completion Date
December 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Collaborators
Carlos III Health Institute, Spanish Clinical Research Network - SCReN
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
Preeclampsia is a leading cause of maternal and neonatal morbidity and mortality worldwide. The morbidity and mortality of this condition arises from two main causes: 1) the lack of specific and sensible methods for its diagnosis and prognosis, 2) and the fact that the course of the disease is often unpredictability at its presentation and speed of progression. The majority of deaths are undoubtedly avoidable and are due to a substandard care. Nowadays it's known that preeclampsia is a placental disorder that is characterized by an unbalance of angiogenic and antiangiogenic factors. It has been recently proven that the ratio of sFlt-1 to PlGF in women who presented with a clinical suspicion of preeclampsia is useful distinguishing between women in whom preeclampsia would develop and those in whom it would not. A low ratio also predicted the absence of fetal adverse outcomes in the same time frame. In addition this ratio demonstrated to be useful to discriminate among patients that would developed maternal or fetal adverse outcome. Correct identification and diagnosis of women at risk could potentially prevent all these adverse outcomes thus, clinical experience suggests that early detection and monitoring are beneficial.
EuroPE aims to provide evidence that the re-definition of pre-eclampsia as an entity caused by a placental unbalance of angiogenic and anti-angiogenic factors and its incorporation in the diagnosis and classification of the disease would improve maternal and neonatal health.
This will be an open, multicentre, international, randomised controlled trial with an intention-to -treat analysis. The study is pragmatic: it will be undertaken to reflect real clinical practice rather than the very tightly controlled circumstances of explanatory trials. The main objective of this study is to determine the effects of the use of the ratio as a diagnostic tool in the definition and classification of PE, as compared with its usual definition, in triage and delivery decisions and to see whether this new approach is able to improve maternal and perinatal outcomes.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Preeclampsia
Keywords
preeclampsia, intrauterine growth restriction, angiogenic factors
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
2536 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Incorporation of the sFlt1/P1GF ratio
Arm Type
Experimental
Arm Description
Incorporation of the ratio in the diagnosis and classification of pre-eclampsia:
sFlt1/PlGF ratio >38: pre-eclampsia risk
sFlt1/PlGF ratio >85: pre-eclampsia
ISSHP pre-eclampsia definition + ratio >210: severe PE
ISSHP pre-eclampsia definition + ratio sFlt1/PlGF ratio >600: consider deliver
Arm Title
Routine clinical practice
Arm Type
No Intervention
Arm Description
Criteria for the definition of PE were those of the International Society for the Study of Hypertension in Pregnancy
Intervention Type
Diagnostic Test
Intervention Name(s)
Placental biomarkers
Intervention Description
sFlt1 and P1GF levels and sFlt1/PlGF ratio
Primary Outcome Measure Information:
Title
Adverse outcomes
Description
Composite score for adverse outcomes defined as the presence of any of the following: premature placental abruption, cessation of abnormal CTG, fetal death, need for 2 or more antihypertensive drugs, eclampsia, disseminated intravascular coagulation, maternal mortality, postpartum haemorrhage (need for more than 2 concentrated hematies), acute pulmonary edema, cerebral vascular hemorrhage, pulmonary embolism, sepsis, ICU admission, need for second surgery.
Time Frame
Up to 24 weeks
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Ability to read and understand informed consent.
Unique pregnancies.
> 24 weeks and <41 weeks
Suspected preeclampsia:
140/90 or worsening of chronic hypertension
Onset of proteinuria (Labstick + or proteinuria> 300mg / 24 hours) or worsening of it
Preeclampsia prodromal clinic such as epigastric, headache, photopsia, tinnitus and increased edema in the face hands or legs or weight gain (> 1 kg per week in the third trimester)
Analytical alterations: decrease in platelets <100,000. Increased transaminases.
Ultrasound alterations: Small fetus for gestational age or restriction of interatrial growth, increased resistance of the uterine arteries.
Pre-eclampsia (ACOG Practice Bulletin 2013)
Exclusion Criteria:
Multiple pregnancies
<24 weeks of gestation
Fetal chromosomal or congenital abnormalities
Conditions that require immediate delivery (eclampsia, pulmonary edema, uncontrolled hypertension, severe visual disturbances, severe headache, fetal demise, non-reassuring fetal status….)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Elisa Llurba, MD, PhD
Phone
+34935537041
Email
ellurba@santpau.cat
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Elisa Llurba, MD, PhD
Organizational Affiliation
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital de la Santa Creu i Sant Pau
City
Barcelona
ZIP/Postal Code
08025
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elisa Llurba, MD, PhD
Phone
+34935537041
Email
ellurba@santpau.cat
12. IPD Sharing Statement
Citations:
PubMed Identifier
24150027
Citation
Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists' Task Force on Hypertension in Pregnancy. Obstet Gynecol. 2013 Nov;122(5):1122-1131. doi: 10.1097/01.AOG.0000437382.03963.88. No abstract available.
Results Reference
background
PubMed Identifier
26735990
Citation
Zeisler H, Llurba E, Chantraine F, Vatish M, Staff AC, Sennstrom M, Olovsson M, Brennecke SP, Stepan H, Allegranza D, Dilba P, Schoedl M, Hund M, Verlohren S. Predictive Value of the sFlt-1:PlGF Ratio in Women with Suspected Preeclampsia. N Engl J Med. 2016 Jan 7;374(1):13-22. doi: 10.1056/NEJMoa1414838.
Results Reference
background
PubMed Identifier
24166751
Citation
Verlohren S, Herraiz I, Lapaire O, Schlembach D, Zeisler H, Calda P, Sabria J, Markfeld-Erol F, Galindo A, Schoofs K, Denk B, Stepan H. New gestational phase-specific cutoff values for the use of the soluble fms-like tyrosine kinase-1/placental growth factor ratio as a diagnostic test for preeclampsia. Hypertension. 2014 Feb;63(2):346-52. doi: 10.1161/HYPERTENSIONAHA.113.01787. Epub 2013 Oct 28.
Results Reference
background
PubMed Identifier
21185591
Citation
von Dadelszen P, Payne B, Li J, Ansermino JM, Broughton Pipkin F, Cote AM, Douglas MJ, Gruslin A, Hutcheon JA, Joseph KS, Kyle PM, Lee T, Loughna P, Menzies JM, Merialdi M, Millman AL, Moore MP, Moutquin JM, Ouellet AB, Smith GN, Walker JJ, Walley KR, Walters BN, Widmer M, Lee SK, Russell JA, Magee LA; PIERS Study Group. Prediction of adverse maternal outcomes in pre-eclampsia: development and validation of the fullPIERS model. Lancet. 2011 Jan 15;377(9761):219-27. doi: 10.1016/S0140-6736(10)61351-7. Epub 2010 Dec 23.
Results Reference
background
Citation
National Institute for Health and Care Excellence guideline DG 23 (2016): PlGF based testing to help diagnose suspected pre-eclampsia (Triage PlGF test, Elecsys immunoassay sFlt-1/PlGF ratio, DELFIA Xpress PlGF 1-2-3 test, and BRHAMS sFlt-1 Kryptor/BRAHMS PlGF plus Kryptor PE ratio). Available at: https://www.nice.org.uk/guidance/dg23/chapter/1-recommendations [Accessed January 2017].
Results Reference
background
PubMed Identifier
25736847
Citation
Stepan H, Herraiz I, Schlembach D, Verlohren S, Brennecke S, Chantraine F, Klein E, Lapaire O, Llurba E, Ramoni A, Vatish M, Wertaschnigg D, Galindo A. Implementation of the sFlt-1/PlGF ratio for prediction and diagnosis of pre-eclampsia in singleton pregnancy: implications for clinical practice. Ultrasound Obstet Gynecol. 2015 Mar;45(3):241-6. doi: 10.1002/uog.14799. No abstract available.
Results Reference
background
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Randomizated Open-label Control Trial to Evaluate if the Incorporation of sFlt1/PlGF Ratio in the Diagnosis and Classification of PE Improves Maternal and Perinatal Outcomes in Women With the Suspicion of the Disease
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