Detection of False Positives From First-trimester Preeclampsia Screening (StopPRE) at the Second-trimester of Pregnancy (StopPRE)

A Phase III, Multicentric, Randomized, Open-label, Parallel-group Clinical Trial to Detect False Positives From First-trimester Preeclampsia Screening (StopPRE) at the Second-trimester of Pregnancy

Pregnant women at a higher risk for pre-eclampsia (PE) should be offered preventive daily treatment with acetylsalicylic acid (ASA) started before 16 weeks of gestation. To select patients at higher risk for PE, multiparametric assessment combining maternal history, biochemical factors and biophysical factors should be used during the first trimester of pregnancy. Multiparametric risk assessments have a detection rate for early-onset PE around 80% at a false positive rate of 10%. Owing to the low prevalence of early-onset and preterm PE, more than 90% of patients considered at high risk, at the first-trimester screening, will not eventually develop PE. Thus, ASA treatment would be innecessary and could be safely discontinued in these patients.

The sFlt-1 to PlGF ratio has a high negative predictive value for PE during the second and third trimester of pregnancy. Thus, it could be used to detect false-positive patients from the first-trimester screening.

This is a multicentric, randomized, open, parallel, controlled, phase III trial, where 1,080 patients under treatment with ASA for being at high risk for preeclampsia from the first-trimester screening, will be candidates to participate. Patients with a sFlt-1/PlGF <38, from 24 to 27+6 weeks of gestation will be randomized at a 1:1 ratio and allocated to either continue ASA until 36 weeks or to stop ASA treatment.

Study Overview

• Status: Completed
• Conditions: Pre-Eclampsia
• Intervention / Treatment: Drug: ASA-withdrawn group

Detailed Description

The main objective of the study is to demonstrate that in patients considered to be at high risk for PE (from the first-trimester screening) and with sFlt-1/PlGF ratio <38, between 24+0 and 27+6 weeks, the incidence of preterm PE, after cessation of the treatment with ASA, will not be superior to that of the control group.

• Study Type: Interventional
• Enrollment (Actual): 974
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Patients older than 18 years old
• Gestational age between 24+0 and 27+6 weeks
• Single pregnancy
• High-risk for pre-eclampsia from the first-trimester screening for pre-eclampsia
• ASA treatment started before or at 16+6 weeks of gestation
• Maternal sFlt-1/PlGF ratio at 24+0-27+6 weeks of gestation
• Signed informed consent

Exclusion Criteria:

• Multiple pregnancy
• Dead and/or fetal polymalformation, including also any fetal genetical and/or chromosomic disease.
• Von Willebrand disease.
• ASA intolerance and /or allergy
• Peptic ulcer
• ASA compliance <50% before inclusion
• Patients with misunderstanding or not able to understand the protocol, including also any condition which could compromise the compliance of the protocol, according to the investigator's opinion.
• No signature of the informed consent

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ASA-withdrawn group; ASA treatment will be withdrawn if patients present an sFlt/PlGF < 38 at 24+0-27+6 weeks of gestation.	Drug: ASA-withdrawn group; Patients whith sFlt/PlGF ratio < 38 at 24+0-27+6 weeks will be randomized into two arms of the trial. Patients allocated in the experimental arm will stop the ASA treatment.; Other Names: sFlt y PlGF ratio less than 38.
No Intervention: ASA group; ASA treatment will continue until 36 weeks of gestation if patients present an sFlt/PlGF ratio < 38 at 24+0-27+6 weeks of gestation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of preterm pre-eclampsia in both arms of the study (ASA vs no ASA).	Rate of pre-eclampsia <37 weeks in pregnant women at high-risk for early-onset PE from the first-trimester screening and ratio sFlt-1/PlGF<38 between 24-27+6 weeks of gestation in both arms of the study (ASA vs no ASA).	From 24+0 weeks of gestation onwards

Collaborators and Investigators

• Sponsor: Hospital Universitari Vall d'Hebron Research Institute
• Investigators: Principal Investigator: Manel Mendoza Cobaleda, MD, PhD, Vall d'Hebron Institut de Recerca (VHIR)

Study record dates

Study Major Dates

• Study Start (Actual): August 20, 2019
• Primary Completion (Actual): January 30, 2022
• Study Completion (Actual): January 30, 2022

Study Registration Dates

• First Submitted: October 25, 2018
• First Submitted That Met QC Criteria: November 12, 2018
• First Posted (Actual): November 14, 2018

Study Record Updates

• Last Update Posted (Actual): February 16, 2022
• Last Update Submitted That Met QC Criteria: February 15, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: pregnant; pre-eclampsia; sFlt-1/PlGF ratio; ASA treatment
• Additional Relevant MeSH Terms: Pregnancy Complications; Hypertension, Pregnancy-Induced; Eclampsia; Pre-Eclampsia
• Other Study ID Numbers: STOPPRE; 2018-000811-26 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No