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

NCT ID: NCT03741179

Last Updated: 2022-02-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 974 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-20
• Study Completion Date: 2022-01-30

Brief Summary

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.

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.

Conditions

Pre-Eclampsia

Study Design

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

Study Groups

ASA-withdrawn group

ASA treatment will be withdrawn if patients present an sFlt/PlGF \< 38 at 24+0-27+6 weeks of gestation.

Group Type: EXPERIMENTAL

ASA-withdrawn group

Intervention Type: DRUG

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.

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

sFlt y PlGF ratio less than 38.

Eligibility Criteria

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

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

Sponsors

Hospital Universitari Vall d'Hebron Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Manel Mendoza Cobaleda, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Vall d'Hebron Institut de Recerca (VHIR)

Locations

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Countries

Spain

References

Mendoza M, Bonacina E, Garcia-Manau P, Lopez M, Caamina S, Vives A, Lopez-Quesada E, Ricart M, Maroto A, de Mingo L, Pintado E, Ferrer-Costa R, Martin L, Rodriguez-Zurita A, Garcia E, Pallarols M, Vidal-Sagnier L, Teixidor M, Orizales-Lago C, Perez-Gomez A, Ocana V, Puerto L, Millan P, Alsius M, Diaz S, Maiz N, Carreras E, Suy A. Aspirin Discontinuation at 24 to 28 Weeks' Gestation in Pregnancies at High Risk of Preterm Preeclampsia: A Randomized Clinical Trial. JAMA. 2023 Feb 21;329(7):542-550. doi: 10.1001/jama.2023.0691.

Reference Type: DERIVED

PMID: 36809321 (View on PubMed)

Other Identifiers

2018-000811-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

STOPPRE

Identifier Type: -

Identifier Source: org_study_id