Endothelial Dysfunction for Prognosis In Patients With preeClampSia

NCT ID: NCT06912477

Last Updated: 2025-05-11

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 385 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-05-08
• Study Completion Date: 2027-07-31

Brief Summary

Preeclampsia is a pregnancy-specific hypertensive disorder and can progress rapidly to severe adverse outcomes affecting both the mother and the fetus. Endothelial and microcirculatory dysfunction mediate systemic preeclampsia-related organ dysfunctions. Changes in endothelial and vascular function in preeclampsia have been demonstrated through reduced flow-mediated vasodilation as a result of reduced availability of nitric oxide, which potentially persists up to several years postpartum. Hyperspectral imaging is a new innovative technology that allows to assess the peripheral microcirculation and perfusion non-invasively and contactless, but has never been evaluated in the context of preeclampsia before.

This EPICS project (Endothelial dysfunction for Prognosis In patients with preeClampSia) is a prospective observational study and aims to investigate hyperspectral imaging as a new potential diagnostic and prognostic marker in preeclampsia.

Detailed Description

Preeclampsia is defined as hypertension combined with features of multi-organ dysfunction and can progress rapidly to severe adverse outcomes affecting both the mother and the fetus. Endothelial dysfunction is a key driver in the pathophysiology of preeclampsia mediating the systemic complications of this multi-organ disease. Changes in endothelial and vascular function in preeclampsia have been observed through reduced flow-mediated vasodilation, which occurs due to diminished nitric oxide availability and may persist for years after childbirth. Although symptoms of preeclampsia often resolve spontaneously after delivery, affected women will face a significantly increased risk of long-term cardiovascular complications. Thus, preeclampsia is viewed as an individual female-specific cardiovascular risk factor.

Beyond this background, hyperspectral imaging as an assessment of peripheral microcirculation and tissue perfusion appears to be a suitable method. Hyperspectral imaging is an innovative technique that visualizes hemodynamic changes by displaying the oxygen saturation of hemoglobin in the capillary system, the distribution of hemoglobin in the tissue, and the relative tissue water content. Hyperspectral imaging has not yet been studied in obstetrics or in the context of preeclampsia before. Given the well-documented microcirculatory disturbances associated with preeclampsia, the investigators hypothesize hyperspectral analysis as a valuable tool to bridge a diagnostic gap that might be useful to tailor individualized obstetric care of patients with preeclampsia.

Recently the "Endothelial Activation and Stress Index" (EASIX) was evaluated as prognostic marker in preeclampsia by the investigator group. EASIX is based on lactate dehydrogenase, platelets, and creatinine and was originally developed as simple score to predict endothelial-related complications after allogenic stem cell transplantation. However, the exact relationship of EASIX to endothelial cell biology and microcirculation requires further clarification. The investigators hypothesize that a reduced peripheral microcirculation will mediate direct interactions of platelets with endothelial cells, resulting in cellular damage (increased LDH), loss of platelets due to activation and microembolism, and lead to kidney damage.

The EPICS study (Endothelial dysfunction for Prognosis In patients with preeClampSia) is the first prospective study to investigate hyperspectral imaging in women with preeclampsia. The aim of this study is to evaluate whether and how changes in microcirculation in women with preeclampsia can be detected with hyperspectral imaging compared to women with pregnancy-induced hypertension, normotensive pregnant women and non-pregnant controls and whether microcirculatory perfusion quality is associated with other biochemical markers such as EASIX or markers of endothelial dysfunction. Furthermore, the EPICS study aims to evaluate the predictive performance of hyperspectral imaging with or without combination of other biochemical markers for adverse maternal and perinatal outcomes and the remaining time until delivery in patients with preeclampsia.

Conditions

Preeclampsia (PE); Hypertensive Disorder of Pregnancy

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Preeclampsia

patients with diagnosis of preeclampsia according to definitions by the International Society for the Study of Hypertension in Pregnancy (n=110)

Hyperspectral imaging

Intervention Type: DIAGNOSTIC_TEST

Hyperspectral imaging will be performed at study inclusion and will be repeated longitudinally every 1-2 days until delivery and on the first and second day after delivery. After a baseline measurement, a blood pressure cuff is inflated on the upper arm to 50 mmHg above the systolic blood pressure for 5 minutes, and then the hyperspectral imaging measurement is repeated.

Blood samples are collected at study inclusion and on the first and second day after delivery and are processed within the Department of Gynecology and Obstetrics of the Heidelberg University Hospital.

Further markers of endothelial dysfunction

Intervention Type: DIAGNOSTIC_TEST

At study inclusion: 1. blood samples will be collected for the measurement of EASIX and cardiac/endothelial markers; 2. sublingual in vivo microscopy will be performed (requires about 20 minutes and can be compared to a sublingual temperature measurement); 3. Doppler ultrasound will be performed to evaluate uterine and ophthalmic arteries.

Blood samples will also be collected at the first and second day after delivery.

Pregnancy induced Hypertension and chronic Hypertension

patients with hypertension in pregnancy without fulfilling criteria of preeclampsia (n=110)

Hyperspectral imaging

Intervention Type: DIAGNOSTIC_TEST

Hyperspectral imaging will be performed at study inclusion and will be repeated longitudinally every 1-2 days until delivery and on the first and second day after delivery. After a baseline measurement, a blood pressure cuff is inflated on the upper arm to 50 mmHg above the systolic blood pressure for 5 minutes, and then the hyperspectral imaging measurement is repeated.

Blood samples are collected at study inclusion and on the first and second day after delivery and are processed within the Department of Gynecology and Obstetrics of the Heidelberg University Hospital.

Further markers of endothelial dysfunction

Intervention Type: DIAGNOSTIC_TEST

At study inclusion: 1. blood samples will be collected for the measurement of EASIX and cardiac/endothelial markers; 2. sublingual in vivo microscopy will be performed (requires about 20 minutes and can be compared to a sublingual temperature measurement); 3. Doppler ultrasound will be performed to evaluate uterine and ophthalmic arteries.

Blood samples will also be collected at the first and second day after delivery.

Normotensive pregnant control group

normotensive pregnancies (n=110)

Hyperspectral imaging

Intervention Type: DIAGNOSTIC_TEST

Hyperspectral imaging will be performed at study inclusion and will be repeated longitudinally every 1-2 days until delivery and on the first and second day after delivery. After a baseline measurement, a blood pressure cuff is inflated on the upper arm to 50 mmHg above the systolic blood pressure for 5 minutes, and then the hyperspectral imaging measurement is repeated.

Blood samples are collected at study inclusion and on the first and second day after delivery and are processed within the Department of Gynecology and Obstetrics of the Heidelberg University Hospital.

Further markers of endothelial dysfunction

Intervention Type: DIAGNOSTIC_TEST

At study inclusion: 1. blood samples will be collected for the measurement of EASIX and cardiac/endothelial markers; 2. sublingual in vivo microscopy will be performed (requires about 20 minutes and can be compared to a sublingual temperature measurement); 3. Doppler ultrasound will be performed to evaluate uterine and ophthalmic arteries.

Blood samples will also be collected at the first and second day after delivery.

Non-pregnant control group

normotensive, non-pregnant women (n=55)

Hyperspectral imaging

Intervention Type: DIAGNOSTIC_TEST

Hyperspectral imaging will be performed at study inclusion and will be repeated longitudinally every 1-2 days until delivery and on the first and second day after delivery. After a baseline measurement, a blood pressure cuff is inflated on the upper arm to 50 mmHg above the systolic blood pressure for 5 minutes, and then the hyperspectral imaging measurement is repeated.

Blood samples are collected at study inclusion and on the first and second day after delivery and are processed within the Department of Gynecology and Obstetrics of the Heidelberg University Hospital.

Further markers of endothelial dysfunction

Intervention Type: DIAGNOSTIC_TEST

At study inclusion: 1. blood samples will be collected for the measurement of EASIX and cardiac/endothelial markers; 2. sublingual in vivo microscopy will be performed (requires about 20 minutes and can be compared to a sublingual temperature measurement); 3. Doppler ultrasound will be performed to evaluate uterine and ophthalmic arteries.

Blood samples will also be collected at the first and second day after delivery.

Interventions

Hyperspectral imaging

Hyperspectral imaging will be performed at study inclusion and will be repeated longitudinally every 1-2 days until delivery and on the first and second day after delivery. After a baseline measurement, a blood pressure cuff is inflated on the upper arm to 50 mmHg above the systolic blood pressure for 5 minutes, and then the hyperspectral imaging measurement is repeated.

Blood samples are collected at study inclusion and on the first and second day after delivery and are processed within the Department of Gynecology and Obstetrics of the Heidelberg University Hospital.

Intervention Type: DIAGNOSTIC_TEST

Further markers of endothelial dysfunction

At study inclusion: 1. blood samples will be collected for the measurement of EASIX and cardiac/endothelial markers; 2. sublingual in vivo microscopy will be performed (requires about 20 minutes and can be compared to a sublingual temperature measurement); 3. Doppler ultrasound will be performed to evaluate uterine and ophthalmic arteries.

Blood samples will also be collected at the first and second day after delivery.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• singleton pregnancies
• Age ≥ 18 years
• Patient's ability to provide consent
• written informed consent

Exclusion Criteria

• Lack of consent
• Language barrier
• Dark to very dark skin type
• Severe fetal chromosomal/genetic/structural anomalies
• Laboratory changes in LDH, creatinine, or platelets due to other causes (e.g., isolated thrombocytopenia, e.g., immune thrombocytopenia, carcinoma)

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Heidelberg University

OTHER

Sponsor Role: lead

Responsible Party

Anna Scholz

Dr. med. Anna Scholz

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Dr. med. Alexandra von Au

Role: PRINCIPAL_INVESTIGATOR

University Heidelberg

Locations

Heidelberg University Hospital, Department of Gynecology and Obstetrics

Heidelberg, , Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Dr. med. Anna Scholz

Role: CONTACT

anna.scholz@med.uni-heidelberg.de

+49 6221 56 32080

Facility Contacts

Dr. med. Anna Scholz

Role: primary

anna.scholz@med.uni-heidelberg.de

+49 6221 56 32080

Alexandra von Au, Dr. med.

Role: backup

alexandra.vonau@med.uni-heidelberg.de

Other Identifiers

S-457/2024

Identifier Type: -

Identifier Source: org_study_id