Molecular Screening Method for Preeclampsia (PREMOM) (PREMOM)

Prospective Clinical Study for the Early Detection of Preeclampsia Based on the Molecular Screening at the First Trimester of Pregnancy

Preeclampsia (PE) is a major obstetric complication with short- and long-term consequences for the mother and the fetus. Early screening tools to reduce its mortality and morbidity, as well as to prevent the life-threatening consequences are needed. Thus, the detection of women at risk of suffering PE is key to apply preventive and treatment strategies. Recently, the maternal contribution to PE based on defective decidualization has been evidenced and new technical approaches developed to detect circulating biomolecules in blood such as RNA fragments. The main objective of this study is to evaluate the diagnostic precision of the molecular profile from the maternal blood analysed for the early screening of early onset preeclampsia (EOPE).

Study Overview

• Status: Active, not recruiting
• Conditions: Preeclampsia
• Intervention / Treatment: Procedure: Peripheral blood collection in cases group; Procedure: Peripheral blood collection in control group

Detailed Description

The hypothesis is that there is a unique molecular profile in peripheral blood specific to women who develop EOPE that allow an early assess woman´s risk of developing this pregnancy complication.

The purposed study is a biomedical, prospective, multicentre, case-control aimed to determine the predictive value and diagnostic precision of the maternal blood molecular profile for the early screening of EOPE. Late-onset preeclampsia (LOPE) and other pregnancy complications (such as preterm birth, intrauterine growth restriction, gestational diabetes, placenta previa, placental abruption, placenta accreta, premature rupture of preterm membranes, antepartum fetal death, uterine rupture and previous vasa, among others) could be analysed as a secondary outcome.

Subjects will be 9585 pregnant women recruited between 9 and 14 gestational weeks. Participants will provide peripheral blood sample at three different times during pregnancy to be characterised at molecular level in the iPremom laboratories (Igenomix Preeclampsia SLU) after their obstetric outcome was known.

Once the 50% of the total enrolment is achieved, an interim analysis will be conducted by an independent external committee. Data will be registered in an electronic Case Report Form (eCRF) specifically designed for this study. Monitoring activities and data verification will be performed during the whole study to ensure data quality, integrity and transparency.

The total estimated duration of the study is 30 months, of which the first 18 months will correspond to the recruitment period of the participants.

• Study Type: Observational
• Enrollment (Estimated): 9585

Contacts and Locations

• Study Contact: Name: Carlos Simón, MD, PhD
• Study Contact Backup: Name: Carla Gomez, BSc, MSc; Phone Number: +34962938210; Email: carla.gomez@ipremom.com

Study Locations

• Spain
  • Albacete, Spain
    • Complejo Hospitalario Universitario de Albacete
  • Albacete, Spain
    • Complejo Hospitalario Universitario Insular Materno Infantil
  • Alicante, Spain
    • Hospital General de Alicante
  • Castellón De La Plana, Spain
    • Hospital General de Castellon
  • Córdoba, Spain
    • Hospital Universitario Reina Sofia
  • Madrid, Spain
    • Hospital Universitario Puerta de Hierro Majadahonda
  • Murcia, Spain
    • Hospital Clínico Universitario Virgen de la Arrixaca
  • Santa Cruz De Tenerife, Spain
    • Hospital Universitario de Canarias
  • Valencia, Spain
    • Hospital Universitario y Politecnico La Fe
  • Valladolid, Spain
    • Hospital del Rio Hortega
  • Zaragoza, Spain
    • Hospital Universitario Miguel Servet
  • Zaragoza, Spain
    • Hospital Clínico Universitario Lozano Blesa
  • Madrid
    • Torrejón De Ardoz, Madrid, Spain
      • Hospital Universitario de Torrejón
  • Murcia
    • Cartagena, Murcia, Spain
      • Hospital General Universitario Santa Lucia
  • Vizcaya
    • Baracaldo, Vizcaya, Spain
      • Hospital Universitario Cruces

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Pregnant women over the age of 18 recruited between 9 and 14 gestational weeks who attend the participating referral centers for their regular gynecological-obstetric follow-up, as well as their childbirth care.

Description

Inclusion Criteria:

• Patients whose written informed consent approved by the Ethics Committee (EC) has been obtained, after having been duly informed of the nature of the study and voluntarily accepted to participate after being fully aware of the potential risks, benefits and any discomfort involved.
• Women over the age of 18 at the time of signing the informed consent form.
• Pregnant women with single gestation between weeks 9 and 14 of gestation.

Exclusion Criteria:

• Known malignancy
• History of organ transplant or bone marrow transplant.
• Maternal transfusion in the last 8 weeks prior to taking the sample.
• Early gestational loss
• Existence of serious or uncontrolled bacterial, fungal or viral infections that, in the opinion of the investigator may interfere with the patient's participation in the study or the evaluation of the results of the study.
• Other circumstances or difficulties that, in the investigator's opinion, may suppose a risk to the subject or reduce the chances of obtaining satisfactory data to achieve the objectives of the study.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cases group; Women recruited between 9 and 14 gestational weeks diagnosed with preeclampsia or other complication at the end of pregnancy	Procedure: Peripheral blood collection in cases group; Maternal peripheral blood will be collected 3 times during pregnancy (1st, 2nd and 3rd trimester) and clinical data compiled in cases group
Control group; Women recruited between 9 and 14 gestational weeks without diagnosis of preeclampsia or other complication at the end of the pregnancy	Procedure: Peripheral blood collection in control group; Maternal peripheral blood will be collected 3 times during pregnancy (1st, 2nd and 3rd trimester) and clinical data compiled in control group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic precision of EOPE at molecular level	Sensitivity, specificity, positive and negative predictive value using the clinical outcome of pregnancy as a "gold standard" parameter	33 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic precision of LOPE and other pregnancy complications at molecular level	Sensitivity, specificity, positive and negative predictive value using the clinical outcome of pregnancy as a "gold standard" parameter	33 weeks
Characterization of molecular profile in maternal blood	Molecular profile (DNA/RNA/proteins/metabolites) associated to gestational age, epidemiological and clinical variables	33 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of candidate biomarkers in the maternal blood for therapy studies.	DNA/RNA/proteins/metabolites	33 weeks

Collaborators and Investigators

• Sponsor: iPremom
• Investigators: Principal Investigator: Tamara Garrido, PhD, iPremom (Igenomix Preeclampsia SLU)

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2021
• Primary Completion (Estimated): January 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: July 23, 2021
• First Submitted That Met QC Criteria: August 3, 2021
• First Posted (Actual): August 4, 2021

Study Record Updates

• Last Update Posted (Actual): January 23, 2024
• Last Update Submitted That Met QC Criteria: January 22, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Blood; Preeclampsia; First trimester; Molecular profile; Early screening; Early onset Preeclampsia (EOPE); Late onset Peeclampsia (LOPE); Circulating RNA (C-RNA)
• Additional Relevant MeSH Terms: Pregnancy Complications; Hypertension, Pregnancy-Induced; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Pre-Eclampsia
• Other Study ID Numbers: IGX1-PRE-CS-20-11

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No