Quantification of Brain and Kidney Perfusion Before, During, and After Hypothermia Treatment in Neonates With Perinatal Asphyxia Using Contrast-enhanced Ultrasound

NCT ID: NCT06611254

Last Updated: 2024-09-24

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 20 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-06-24
• Study Completion Date: 2027-12-01

Brief Summary

In this clinical study vascular dynamics in the neonatal brain and kidney will be monitored by CUES and ULM before, during and after hypothermia treatment in neonates with asphyxia.

Detailed Description

Perinatal asphyxia (PA) is the reduced supply of oxygen to vital organs during or immediately after birth. PA is one of the most common causes of neonatal mortality in full-term infants worldwide and of hypoxic-ischemic encephalopathy (HIE) with subsequent neurological deficits (spastic cerebral palsy). In addition to brain damage, perinatal asphyxia often leads to dysfunction of other organs. It is not uncommon for this to be accompanied by transient renal failure.

Hypothermia treatment is an established therapeutic measure for neuroprotection in clinical indications of HIE. This involves lowering the core body temperature of affected children to 33.5°C for 72 hours. The therapeutic effect is thought to be due to multifactorial mechanisms, including a reduction in endothelial dysfunction, reduced excretion of free radicals and attenuation of the inflammatory cascade.

In the guidelines for hypothermia treatment in neonatal asphyxia, regular ultrasound examinations are prescribed to clarify damage to the central nervous system (CNS) before, during and after hypothermia treatment.1 In infants, transfontal ultrasound makes it possible to visualize brain structures, vessels and their flow velocities.

The intravenous use of ultrasound contrast enhancers as an aid also opens up the possibility of recording the tissue perfusion of the CNS and kidneys, including the smallest vessels.8 This could provide significantly more information compared to conventional methods and expand our knowledge of the pathophysiology and individual status of tissue perfusion in patients.

For example, two studies at Erlangen University Hospital have successfully used contrast-enhanced ultrasound (CEUS) with the contrast agent known as SonoVue® to visualize postoperative perfusion of the brain after pediatric cardiac surgery.

In this clinical study, the new CEUS measurement and imaging technique will be used before, during and after hypothermia treatment in neonates with asphyxia. A contrast agent (SonoVue®) will be administered during the routine ultrasound examination and improved tissue visualization will be achieved. The aim is to gain new insights into brain and kidney perfusion as part of the treatment and to better assess the extent of organ damage in the individual patient through more specific vascular imaging. Improved visualization and assessment of the end-stream area will provide information on processes that promote the development of HIE and renal failure. Finally, the aim is to compare diagnostic and prognostic methods with the currently recommended measures. The CEUS is to be examined as a possible diagnostic imaging tool and possibly a supplement to existing diagnostic methods.

Conditions

Perinatal Asphyxia; Hypothermia Treatment; Gestational Age Min. 36SSW

Study Design

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

Study Groups

Neonates with perinatal asphyxia and indication for hypothermia treatment

Included will be neonates with perinatal asphyxia that get an indication for hypothermia treatment (severe azidosis and signs of encephalopathy and under 6h of age and \>36 gest. weeks). They will be monitored with CEUS/ULM at three different time points (T1: within first 6h of life/before hypothermia treatment, T2 = during hypothermia treatment/6-78h of life, T3 = after hypothermia treatment/within first week of life.

Contrast enhanced ultrasound imaging (CEUS) and post processing with ULM

Intervention Type: DEVICE

CEUS is a contrast based ultrasound technique and ULM (Ultrasound Localization Microscopy) is a post-processing bioinformatical method to quantify microvascular architecture and perfusion dynamics.

Interventions

Contrast enhanced ultrasound imaging (CEUS) and post processing with ULM

CEUS is a contrast based ultrasound technique and ULM (Ultrasound Localization Microscopy) is a post-processing bioinformatical method to quantify microvascular architecture and perfusion dynamics.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Severe acidosis (pH ≤7.0 or a base deficit ≥16 mmol/l) in umbilical cord blood or a blood sample from the first hour of life, and
• clinical signs of moderate or severe encephalopathy (severity grade 2 or 3 according to Sarnat & Sarnat), and
• postnatal age ≤6h, and
• gestational age ≥36 weeks' gestation
• Consent of the parents/legal guardians
• Time 1 (before the start of hypothermia treatment)

• Informing the parents/legal guardians present on site despite an emotionally stressful situation with high individual benefit for the patient
• If only one parent is present and able to provide information, their consent is sufficient - the second parent is informed repeatedly when they regain the ability to provide information
• Information adapted to the emergency situation, addressing the personal situation and comprehensible presentation of the plan
• Time 2 (during hypothermia treatment)

-->Offer of a further informative discussion/repeated explanation with the parents/legal representatives before the second measurement in order to answer any questions that may have arisen

• Suitable acoustic window
• Availability of the qualified examiner

Exclusion Criteria

• Lack of consent of at least one parent
• Pre-existing brain malformations
• Absence of the competent examiner

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Erlangen-Nürnberg Medical School

OTHER

Sponsor Role: lead

Responsible Party

Ferdinand Knieling

Principal Investigator, Pediatric Translational Imaging Laboratory

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ferdinand Knieling, MD

Role: PRINCIPAL_INVESTIGATOR

FAU Erlangen-Nuernberg

Gregor Hanslik, MD

Role: PRINCIPAL_INVESTIGATOR

FAU Erlangen-Nuernberg

Locations

FAU Erlangen-Nuernberg

Erlangen, Bavaria, Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Ferdinand Knieling, MD

Role: CONTACT

ferdinand.knieling@uk-erlangen.de

0049 9131 85 33118

Gregor Hanslik, MD

Role: CONTACT

gregor.hanslik@uk-erlangen.de

0049 9131 85 33118

Facility Contacts

Ferdinand Knieling, MD

Role: primary

ferdinand.knieling@uk-erlangen.de

0049 9131 85 33118

Other Identifiers

Neo_CEUS_ULM

Identifier Type: -

Identifier Source: org_study_id