Light Utilization COX-Inhibitory Device Therapy for Infant Cardiac Arrest (LUTICA Study). The LUCID Device is Used in the Treatment of Ischemic Brain Reperfusion Injury Caused by Cardiac Arrest in Pediatric Patients.

Официальное название

Light Utilization COX-Inhibitory Device Therapy for Infant Cardiac Arrest (LUTICA Study)

Обзор

Approximately 15,200 children receive cardiopulmonary resuscitation (CPR) for in-hospital cardiac arrest (IHCA) each year in the United States. Of these, about 60% are less than one year of age. Most IHCA (85-90%) occurs in intensive care units (ICU) or other monitored settings. Risk of IHCA is higher among children with cardiac disease compared to children with other diagnoses. A report based on the Pediatric Cardiac Critical Care Consortium (PC4) registry found 3.1% of children hospitalized in pediatric cardiac ICUs had a cardiac arrest; rates varied from 1% to 5.5 % across sites. Survival to hospital discharge after CA in children included in the PC4 registry was 53%, and lower for medical cardiac patients (37.7%) than for surgical cardiac patients (62.5%). Among survivors of pediatric IHCA, neurologic morbidities are common including cognitive, motor, and adaptive functional deficits. Despite high mortality and morbidity, treatment for children after IHCA is mainly supportive. Preventing fever and hypotension, maintaining normoxia, and treating seizures are emphasized. Ischemia-reperfusion injury to the brain is a primary cause of neurologic morbidity after IHCA. Ischemia-reperfusion leads to increased production of cytotoxic mitochondrial reactive oxygen species (ROS). Recently, specific wavelengths of near infrared light (NIR) (750 nm and 950 nm) have been discovered to partially inhibit cytochrome c oxidase activity (COX), reversibly reducing mitochondrial respiration and generation of ROS. Light Utilization COX Inhibitory Device (LUCID) is a novel medical device intended to safely deliver therapeutic NIR to the infant brain to prevent reperfusion injury. This protocol describes the "LUCID Therapy for Infant Cardiac Arrest" (LUTICA) clinical trial. LUTICA will investigate the safety, feasibility, acceptability, and probable benefit of the LUCID device in infants with acquired or congenital cardiac disease who experience unplanned IHCA. The hypothesis of the LUTICA trial is that application of the LUCID light box and cap immediately following IHCA in infants with acquired or congenital heart disease will be safe, feasible, and acceptable in the ICU setting, and demonstrate probable benefit toward favorable neurological outcomes.

Подробное описание

LUCID is a device designed to deliver therapeutic NIR light (750 nm and 950 nm) to the brain of infants to provide neuroprotection following cardiac arrest and resuscitation. LUCID consists of two distinct parts: (1)Human interface, and (2) Light source and user interface.

The human interface will deliver therapeutic NIR light directly to the infant's head. The light delivery areas distribute the light to ensure uniform distribution, dose, and safety. LUCID is compatible with EEG monitoring and protective eye covering. It is an appropriate size and weight for clinical use, and capable of battery operation which will allow patient transport and incorporation into seamless clinical workflow.

The light source and user interface contain laser diodes producing the therapeutic wavelengths with thermoelectric and air cooling to prolong the lifetime of the diodes and provide temperature control. LUCID also contains a user interface/control panel. Power supply is via standard power outlet.

The LUCID control module is equipped with a simple, user-friendly interface for initiating the treatment as well as system feedback to ensure proper function of the device and therapeutic delivery. The system has a main power switch located on the front of the device which engages power to the diode subassemblies, enables system thermoregulation components, and runs a quick system self-check. The healthcare provider will place and secure the cap on the infant's head and connect the light source to the human interface. Once the cap has been properly connected to the light source, the connection indicator will illuminate, signaling that the treatment is ready to initiate. Once treatment is initiated by the user, the user interface will monitor contact, light, and temperature sensors in the cap to ensure the device is operating within designated safe and effective treatment parameters. If abnormalities are detected, the unit will disengage treatment. Clinician oversight is required during the treatment period to monitor the patient and system. Normal system operation shows a visible treatment countdown timer on the front panel to document a full 4-hour treatment. The system logs treatment duration, date and time of treatment for documentation of therapeutic delivery and system performance.

The system will automatically terminate therapeutic NIR light at the end of the 2-hour treatment, and the system will notify the user when treatment has stopped. Errors in the system that would initiate safety shutdown include loss of LDU contact with the patient's skin, light loss or excess at the light delivery patient interface, system overheating, diode failure, or active system cooling failure. The user interface will indicate treatment interruption with an error LED and audio indicator, along with documentation in the run log including the error code with time to document the duration of treatment interruption and the dose the patient received. To provide eye protection during LUCID treatment, eye masks such as the EyeMax-2 or NeoShades (routinely used in infants undergoing phototherapy for hyperbilirubinemia) will be placed on the infant. Eyewear for the clinician is recommended but not required.

The LUCID system consists of 2 primary components:

1. Lightbox: This multiple use component generates the 750 (+/- 10) and 940 (+/- 10) nanometer light delivered to the patient via a fiberoptic cable (interface cable) connected to the cap. The Lightbox includes the user interface and control electronics that ensure the specific amount of light is delivered and all safety measures are being performed. 2. Cap: This single use device employs light guides that diffuse and direct the light into the patient's head during treatment. The Cap includes silicone waveguides (Light Delivery Units - LDU's) that direct therapeutic light into the patient and returns specific measurements (GOOD CONTACT indicator, temperature, light levels) to the Lightbox.

Вмешательства

• Устройство LUTICIA - Light Utilization COX-Inhibitory Device)
  Light Utilization COX Inhibitory Device (LUCID) is a novel medical device intended to safely deliver therapeutic NIR to the infant brain to prevent reperfusion injury. The therapy is designed to deliver therapeutic NIR light (750 nm and 950 nm) to the brain of infants to provide neuroprotection following cardiac arrest and resuscitation. LUCID consists of two distinct parts: (1) Human interface, and (2) Light source and user interface. The human interface will deliver therapeutic NIR light dire

Первичные конечные точки

• Safety Endpoint: Scalp Temperature [Срок оценки: 2 hours during treatment]
• Change from Baseline in Pediatric Cerebral Performance Category (PCPC) Scale [Срок оценки: The study will be conducted in hospital at screening, discharge, and then at 3 months, 1 year, and 2 years.]
• Change from Baseline in Pediatric Overall Performance Category (POPC) Scale [Срок оценки: Assessments will be conducted at screening, discharge, 3 months, 1 year, and 2 years post-intervention.]
• Change from Baseline in Vineland Adaptive Behavior Scale III (VABS-3) [Срок оценки: Assessments will be conducted at screening, discharge, 3 months, 1 year, and 2 years post-intervention.]
• Change from Baseline in Hammersmith Neonatal Neurological Exam (HNNE) or Hammersmith Infant Neurological Exam (HINE) [Срок оценки: Assessments require an in-person examination and will be conducted at screening, discharge, 3 months, 1 year, and 2 years post-intervention.]

Вторичные конечные точки (9)

• Secondary Endpoint 1: Number of Participants With Local Scalp Wound Development [Срок оценки: From baseline (pre-treatment) through Day 28 or PICU/CICU discharge]
• Secondary Endpoint 2: All-Cause 28-Day Mortality [Срок оценки: 28 days]
• Secondary Endpoint 3: Feasibility of Protocol Adherence: Proportion of Participants Completing Treatment [Срок оценки: 28 days]
• Secondary Endpoint 4: Acceptability [Срок оценки: 7 days]
• Secondary Endpoint 5: Vineland Adaptive Behavior Scales Third Edition [Срок оценки: 3 months]
• Secondary Endpoint 6: Pediatric Resuscitation after Cardiac Arrest Scale [Срок оценки: 3 months]
• Secondary Endpoint 7: Neurological Status as Assessed by Murray's EEG Grading Criteria [Срок оценки: 3 months]
• Secondary Endpoint 8: Incidence of Elevated Neuro-injury Biomarker Levels [Срок оценки: 24 hours and 7 days]
• Secondary Endpoint 9: Presence of Ischemic Brain Injury as Assessed by Clinical Neuroimaging (CT/MRI) [Срок оценки: 3 months]

Критерии участия

Критерии включения

Subjects must meet ALL of the following criteria to be eligible for participation in the study:

• In advance of the IHCA, a consent form signed by the Legally Authorized Representative (LAR) such as a parent/guardian will be attained.
• Age greater than 48 hours and less than 1 year (with a corrected gestational age of at least 38 weeks).
• Greater than or equal to 2.5 kg body weight.
• Acquired or congenital heart disease.
• Society of Thoracic Surgeons- European Association for Cardio-Thoracic Surgery (STAT) categories 4 and 5" and those patients with medical cardiac conditions with an admission diagnosis of acute heart failure, if blood lactate levels are greater than 3 mmol/L, or if mechanically ventilated within 4 hours of admission.
• Chest compressions for at least 2 minutes (120 seconds) during IHCA with ROC; Modified Glasgow Coma Scale for Infants and Children will be used to determine eligibility.
• Coma or encephalopathy after ROC. Coma or encephalopathy after ROC, Modified Glasgow Coma Scale for Infants and Children will be used to determine eligibility.
• Requires mechanical ventilation (i.e., via endotracheal tube or tracheostomy).
• The cardiac arrest was unplanned (i.e., not part of cardiac surgical procedure).
• A patient with a condition in which direct contact with the scalp is contraindicated such as decubitus ulcers, cellulitis, cuts, nicks, scratches, or other conditions with disrupted scalp integrity, will not be eligible for treatment, but will be eligible for the study and data collected will be used as control data.

Критерии исключения

Subjects must be EXCLUDED from participation in this study if ANY of the following criteria are met:

• The Legally Authorized Representative does not speak English or Spanish
• The LUCID cap is impossible to place within two (2) hours of ROC.
• Preterm neonates (with a corrected gestational age of less than 38 weeks) due to the potential incompatibility with cap sizes, lack of information on depth of targeted brain structures, potential for waveguide overlap, and increased skin frailty.
• Patients with a head size outside of the range of cap requirements: 32-49cm.
• Modified Glasgow Coma Scale for Infants and Children motor response of six (infants, normal spontaneous movement) prior to treatment.
• Duration of chest compressions greater than 60 minutes inclusive of ECMO deployment.
• Pre-existing severe neurodevelopmental deficits with PCPC = 5 or progressive degenerative encephalopathy.
• Central nervous system tumor with ongoing chemotherapy or radiation therapy.
• Pre-existing terminal illness with life expectancy < 3 months.
• Progressive degenerative encephalopathy.
• Cardiac arrest was associated with severe brain, thoracic, or abdominal trauma
• Active and refractory severe bleeding prior to treatment.
• Continuous infusion of epinephrine or norepinephrine at very high doses (≥ 2 μg/kg/minute).
• Patient is newborn with acute birth asphyxia.
• Patient cared for in a neonatal intensive care unit (NICU) after arrest (i.e., would not be admitted to PICU).
• Patient has sickle cell anemia.
• Patient known to have pre-existing cryoglobulinemia.
• Patient known to have progressive degenerative encephalopathy.
• Patient is known to have neurological issues including convulsions/epileptic seizures, intraventricular hemorrhage, Hypoxic-ischemic encephalopathy, periventricular leukomalacia, and retinopathy of prematurity.
• Patient is known to have a recorded temperature at treatment/LDU site out of range.
• Lack of commitment to aggressive intensive care therapies including do not resuscitate orders and other limitations to care.
• History of a prior cardiac arrest with chest compressions for at least two minutes during the current hospitalization but outside the 2-hour window for treatment.
• Patient cared for in a neonatal intensive care unit (NICU) after arrest (i.e., not admitted to pediatric ICU (PICU)/CICU).
• Patients with prior or concurrent enrollment in any other neurotherapeutic trial, which may confound this study's results and expose patients to the unknown risks of multiple investigational treatments.
• Patient participation in a concurrent interventional trial whose protocol, in the judgment of the LUCID investigators, prevents effective application of LUCID, or otherwise significantly interferes with carrying out the LUCID protocol. We will use the Neonatal Adverse Event Severity Scale.
• Previous enrollment in or termination from LUTICA trial.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Профилактика

Центры проведения

США · 1 центр

• Children's Hospital of Michigan (Detroit) — Detroit

Публикации

• Sanderson TH, Wider JM, Lee I, Reynolds CA, Liu J, Lepore B, Tousignant R, Bukowski MJ, Johnston H, Fite A, Raghunayakula S, Kamholz J, Grossman LI, Przyklenk K, Huttemann M. Inhibitory modulation of cytochrome c oxidase activity with specific near-infrared light wavelengths attenuates brain ischemia/reperfusion injury. Sci Rep. 2018 Feb 22;8(1):3481. doi: 10.1038/s41598-018-21869-x. PMID 29472564
• Wider JM, Gruley E, Morse PT, Wan J, Lee I, Anzell AR, Fogo GM, Mathieu J, Hish G, O'Neil B, Neumar RW, Przyklenk K, Huttemann M, Sanderson TH. Modulation of mitochondrial function with near-infrared light reduces brain injury in a translational model of cardiac arrest. Crit Care. 2023 Dec 14;27(1):491. doi: 10.1186/s13054-023-04745-7. PMID 38098060

Идентификаторы

NCT: NCT07556939 · G240289 · U44NS125160

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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