Vascular Biomarkers Predictive of the Progression From Hypertensive Disorders in Pregnancy to Preeclampsia in Pregnant Women

NCT04520048 | Recruiting

• 2 other identifiers: APHP2002372019-A03207-50
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 3

Brief Summary

Hypertension during pregnancy remains a leading cause of maternal and fetal morbidity and mortality. The frequency (5 to 10% of pregnancies) and potential severity of these diseases, both for the mother and the child, are reasons for standardizing and optimizing medical practices. The cause of hypertension during pregnancy is quite complex, as it depends on a number of factors. Among the hypertensive disorders in pregnancy (HDP), the pathophysiology of pre-eclampsia (one of the most studied in terms of severity) remains poorly understood. The evolution of international guidelines in recent years has made it possible to distinguish various HDP, but schematically we distinguish two main entities by the existence of proteinuria from and after the 20th week of amenorrhea and by maternal-fetal complications, more serious in pre-eclampsia than in gestational hypertension. Acute placental vasculature and blood flow abnormalities were observed during gestational hypertension and preeclampsia, and maybe due to generalized vascular endothelial activation and vasospasm resulting in systemic hypertension and organ hypoperfusion. Endothelial dysfunction (ED) and abnormal expression of several specific blood biomarkers are now well accepted as characteristics of preeclampsia as a leader. However, the progression of any HDP to preeclampsia is possible, but difficult to predict. By way of example, among between 15 and 40 % of gestational hypertension cases progress to preeclampsia, suggesting that it is the same worsening disease. ED could be pre-existing (chronic, white-coat or masked hypertension) but also at the origin of gestational hypertension (unclassified hypertension, transient pregnancy hypertension), and subsequent development of preeclampsia through an imbalance between pro- and anti-angiogenic factors. An imbalance of pro-angiogenic and anti-angiogenic proteins can testify to ED, as can adequate levels of endothelial microparticles. The main objective of this research is to assess the presence of urinary endothelial microparticles in stable pregnant women with hypertensive disorder of pregnancy as a marker for the occurrence of pre-eclampsia during pregnancy.

Conditions

Hypertension Disorders in Pregnancy; Gestational Hypertension; Pre-Eclampsia

Keywords

Hypertension disorders in pregnancy; Gestational hypertension; Pre-eclampsia; Urinary endothelial microparticules; Endothelial dysfunction; Angiogenic biomarkers; Soluble Fms-like- tyrosine kinase 1; Placental Growth Factor; Vascular Endothelial Growth Factor; Microcirculation

Outcome Measures

Primary Outcomes (1)

• Change in the UEMP levels between 26th ± 2 week and 34th ± 2 week of pregnancy.

  Quantification of UEMP by flow cytometry in urine collected at 26 ± 2 week and 34th ± 2 week of amenorrhea.

  change between the 26th ± 2 week of amenorrhea and 34th ± 2 week of amenorrhea

Secondary Outcomes (13)

• Change in circulating levels of soluble Fms-like tyrosine kinase (sFlt-1) between 26 weeks and 34 weeks of pregnancy

  change between the 26th ± 2 week and 34th ± 2 week of amenorrhea

• Change in circulating Placental Growth factor (PIGF) between 26 weeks and 34 weeks of pregnancy

  change between the 26th ± 2 week and 34th ± 2 week of amenorrhea

• Change in circulating levels of vascular endothelial growth factors (VEGF) between 26 weeks and 34 weeks of pregnancy

  change between the 26th ± 2 week and 34th ± 2 week of amenorrhea

• Change in circulating levels of soluble endogline (sEng) between 26 weeks and 34 weeks of pregnancy

  change between the 26th ± 2 week and 34th ± 2 week of amenorrhea

• Change in angiotensin II receptor (AT1) between 26 weeks and 34 weeks of pregnancy

  change between the 26th ± 2 week and 34th ± 2 week of amenorrhea

Study Arms (1)

Women with a hypertension disorder in pregnancy and/or preeclampsia

EXPERIMENTAL

Pregnant patients from the 20th week of amenorrhea with the initial diagnosis of a hypertension disorder in pregnancy and/or preeclampsia. Patients in a stable state undergoing follow-up consultation (day hospital and week hospitalization)

Other: Determination of the UEMP levels; Procedure: Aortic central pressure and the carotid-femoral pulse wave velocity; Other: Vascular biomarker assay; Procedure: Measurement of the uterine artery diameter

Interventions

Determination of the UEMP levels OTHER

Quantification of UEMP by flow cytometry in urine (10 ml) collected at 26 ± 2 week and 34th ± 2 week of amenorrhea.

Women with a hypertension disorder in pregnancy and/or preeclampsia

Aortic central pressure and the carotid-femoral pulse wave velocity PROCEDURE

Measurement of the aortic central arterial pressure (systolic and diastolic arterial pressure) by applanation tonometry, and the index of aortic increase by applanation tonometry, the carotid-femoral pulse wave velocity using the SphygmoCor® system (PWV Medical) and/or Popmetre.

Women with a hypertension disorder in pregnancy and/or preeclampsia

Vascular biomarker assay OTHER

Plasma angiogenic biomarker levels determination using an immunoassay, including circulating sFlt-1, circulating PIGF, sFlt-1 / PIGF ratio, circulating VEGF, circulating soluble endoglin (sEng), other biomarkers assessment, including anti-angiotensin II receptor (AT1), circulating copeptin, circulating interleukin 17 (IL-17), Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL), as well as CEMP and CEC quantification using flow cytometry.

Women with a hypertension disorder in pregnancy and/or preeclampsia

Measurement of the uterine artery diameter PROCEDURE

This measurement is added to the routine examination of the uterine artery. Bi-dimensional ultrasound imaging with angio-Doppler allows the study of the artery as the blood flow velocity and vessel diameter. Uterine artery Doppler pulsatility index (UtA-PI), mean flow velocity and diameter measurement could be calculated with Doppler instrument with software could determine instantaneous true mean blood flow velocity. Measurement is made by placing the cursor from outer edge to outer edge of the artery adventitia, on a cross-section and taking the largest diameter

Women with a hypertension disorder in pregnancy and/or preeclampsia

Eligibility Criteria

• Age: 18 Years - 40 Years
• Gender Eligibility Details: Pregnant women
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients with a hypertension disorder in pregnancy and/or preeclampsia from the 20th amenorrhea week until the 26th ± 2 amenorrhea week.
• Age between 18 and 40 years old.
• Having given written consent.
• Patients affiliated to a social security scheme.

You may not qualify if:

• Presence of pathologies interfering in a major way with vascular parameters: known multicomplicated diabetes treated before pregnancy, hypercholesterolemia known (or LDL\>130 mg/dl), multicomplicated connectivitis, proven cardiovascular disease (ischemic heart disease, stroke, arteriopathy of the lower limbs, heart failure), pre-existing known renal failure (serum creatinine \>125 µmol/L) and/or pre-existing proteinuria ≥ 300 mg/24h).
• Cardiac arrhythmia.
• Hepatitis C, HIV infection (assay performed within 6 months prior to diagnosis of pre-eclampsia).
• Recent history of venous (pulmonary embolism, phlebitis) or arterial (myocardial infarction, unstable angina, stroke, transient ischemic attack), thrombotic event ≤ 3 months.
• Patient already engaged in a therapeutic protocol.
• Patients under legal protective measures.
• Patients receiving State Medical Assistance.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (3)

AP-HP Avicenne Hospital, Department of internal medicine

Bobigny, Seine Saint Denis, 93000, France

RECRUITING

AP-HP Jean Verdier Hospital, Gynecology and Obstetrics Department

Bondy, Seine Saint Denis, 93140, France

RECRUITING

AP-HP Laribosière Hospital, Gynecology and Obstetrics Department

Paris, 75010, France

RECRUITING

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MeSH Terms

Conditions

Hypertension, Pregnancy-Induced; Pre-Eclampsia

Condition Hierarchy (Ancestors)

Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Marilucy LOPEZ-SUBLET, MD

  AP-HP Avicenne Hospital, Department of Internal Medicine, ESH Hypertension European Excellence Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marilucy LOPEZ-SUBLET, MD

CONTACT

+33 (0)148955391; marilucy.lopez-sublet@aphp.fr

Lionel CARBILLON, MD PhD

CONTACT

+33 (0)148026030; lionel.carbillon@aphp.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2020
• First Posted: August 20, 2020
• Study Start: August 11, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: September 12, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (3)