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

Обзор

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.

Подробное описание

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.

Вмешательства

• Устройство 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.

Первичные конечные точки

• CEUS Time intensity curves [Срок оценки: before(T1, within the first 6hours of life), during hypothermia treatment(T2, 6-78hours of life), after treatment (T3, within first week of life)]
• CEUS Measurement1 [Срок оценки: before(T1, within the first 6hours of life), during hypothermia treatment(T2, 6-78hours of life), after treatment (T3, within first week of life)]
• CEUS Measurement2 [Срок оценки: before(T1, within the first 6hours of life), during hypothermia treatment(T2, 6-78hours of life), after treatment (T3, within first week of life)]
• CEUS Measurement3 [Срок оценки: before(T1, within the first 6hours of life), during hypothermia treatment(T2, 6-78hours of life), after treatment (T3, within first week of life)]
• CEUS Measurement4 [Срок оценки: before(T1, within the first 6hours of life), during hypothermia treatment(T2, 6-78hours of life), after treatment (T3, within first week of life)]
• CEUS Measurement5 [Срок оценки: before(T1, within the first 6hours of life), during hypothermia treatment(T2, 6-78hours of life), after treatment (T3, within first week of life)]
• CEUS Measurement6 [Срок оценки: before(T1, within the first 6hours of life), during hypothermia treatment(T2, 6-78hours of life), after treatment (T3, within first week of life)]
• CEUS Measurement7 [Срок оценки: before(T1, within the first 6hours of life), during hypothermia treatment(T2, 6-78hours of life), after treatment (T3, within first week of life)]
• CEUS Measurement8 [Срок оценки: before(T1, within the first 6hours of life), during hypothermia treatment(T2, 6-78hours of life), after treatment (T3, within first week of life)]
• CEUS Measurement9 [Срок оценки: before(T1, within the first 6hours of life), during hypothermia treatment(T2, 6-78hours of life), after treatment (T3, within first week of life)]

Вторичные конечные точки (12)

• CEUS and NIRS [Срок оценки: T1,T2,T3]
• Neurological status assessment (Bayley Score) [Срок оценки: Month of life: 3-4 and 6-24]
• MRI imaging in asphyxia [Срок оценки: once within first two years of life]
• Comparison of the CEUS time-intensity curve between three timepoints [Срок оценки: T1,T2, T3]
• Assessment of blood Lactate [Срок оценки: T1, T2, T3]
• EEG signs of seizures [Срок оценки: T1 -T3 and through study completion]
• EEG activity [Срок оценки: T1 -T3 and through study completion]
• Assessment of renal function GFR [Срок оценки: T1 -T3 and through study completion, an average of 3 years]
• Assessment of renal function urea [Срок оценки: T1 -T3 and through study completion, an average of 3 years]
• Assessment of renal function urinary status [Срок оценки: T1 -T3 and through study completion]
• Assesment of renal function kreatininekinase [Срок оценки: T1, T2, T3]
• Assessment of metabolic LDH [Срок оценки: T1, T2, T3]

Критерии участия

Критерии включения

• Fulfillment of the inclusion criteria for hypothermia treatment according to the AWMF guideline
• 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

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Германия · 1 центр

• FAU Erlangen-Nuernberg — Erlangen

Идентификаторы

NCT: NCT06611254 · Neo_CEUS_ULM

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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