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

NCT ID: NCT03231657

Last Updated: 2023-12-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 2536 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-06
• Study Completion Date: 2023-11-11

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.

Conditions

Preeclampsia

Keywords

preeclampsia; intrauterine growth restriction; angiogenic factors

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Incorporation of the sFlt1/P1GF ratio

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

Group Type: EXPERIMENTAL

Placental biomarkers

Intervention Type: DIAGNOSTIC_TEST

sFlt1 and P1GF levels and sFlt1/PlGF ratio

Routine clinical practice

Criteria for the definition of PE were those of the International Society for the Study of Hypertension in Pregnancy

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Placental biomarkers

sFlt1 and P1GF levels and sFlt1/PlGF ratio

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• Ability to read and understand informed consent.
• Unique pregnancies.
• > 24 weeks and <41 weeks
• Suspected preeclampsia:

1. 140/90 or worsening of chronic hypertension

2. Onset of proteinuria (Labstick + or proteinuria> 300mg / 24 hours) or worsening of it

3. 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)

4. Analytical alterations: decrease in platelets <100,000. Increased transaminases.

5. 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….)

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Carlos III Health Institute

OTHER_GOV

Sponsor Role: collaborator

Spanish Clinical Research Network - SCReN

NETWORK

Sponsor Role: collaborator

Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Elisa Llurba, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

Locations

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Countries

Spain

References

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.

Reference Type: BACKGROUND

PMID: 24150027 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 26735990 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24166751 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21185591 (View on PubMed)

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].

Reference Type: BACKGROUND

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.

Reference Type: BACKGROUND

PMID: 25736847 (View on PubMed)

Other Identifiers

IIBSP-EUR-2017-20

Identifier Type: -

Identifier Source: org_study_id