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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
PREVENTION
Masking
NONE
Enrollment
30
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 directly to the infant's head. The light delivery areas distribute the light to ensure uniform distribution, dose, and safety.
Children's Hospital of Michigan (Detroit)
Detroit, Michigan, United States
Safety Endpoint: Scalp Temperature
LUCID is designed to monitor and record scalp surface temperature directly at the light delivery patient interface. A control temperature probe will be placed with a small adhesive patch on the skin below the jaw to measure patient skin temperature at a location remote from treatment. A temperature deviation less than 2°C at the control site throughout the treatment will be an indicator of safety success.
Time frame: 2 hours during treatment
Change from Baseline in Pediatric Cerebral Performance Category (PCPC) Scale
The PCPC is a 6-point scale of increasing disability (1=good/normal, 6=death). This scale is used to assess neurologic functioning.
Time frame: 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
The POPC is a 6-point scale of increasing disability (1=good/normal, 6=death). This scale is used to assess overall health status. Assessments will be conducted at discharge, 3 months, 1 year, and 2 years post-intervention.
Time frame: 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)
Description: The VABS-3 is an assessment tool used to evaluate adaptive behavior and functional skills.
Time frame: 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)
The HNNE/HINE is a clinical assessment of neurological function.
Time frame: Assessments require an in-person examination and will be conducted at screening, discharge, 3 months, 1 year, and 2 years post-intervention.
Secondary Endpoint 1: Number of Participants With Local Scalp Wound Development
Incidence of local wound development as determined by clinical examination: The scalp will be examined prior to placing the LUCID cap, every 30 minutes during the treatment, at the time of removal of the cap, 6-8 hours later, daily for 7 days, weekly through day 28 (or PICU/CICU discharge, whichever occurs first). If wound development occurs, documentation will include location, stage, size, base tissues, exudates, edge/perimeter, pain and evidence of infection. Documentation of wounds and treatment will be gathered by hospital clinicians and included in the study report. Absence of local wound development will be an indicator of safety success. Per protocol, the scalp will be examined prior to placing the cap, every 30 minutes during treatment, at removal, 6-8 hours later, and through Day 28. "Wound development" includes documentation of location, stage, size, and infection. Absence of local wound development is an indicator of safety success.
Time frame: From baseline (pre-treatment) through Day 28 or PICU/CICU discharge
Secondary Endpoint 2: All-Cause 28-Day Mortality
All-cause mortality at day 28 after ROC will be recorded and compared to historical controls. No numerical increase in mortality compared to historical controls will be an indicator of safety success
Time frame: 28 days
Secondary Endpoint 3: Feasibility of Protocol Adherence: Proportion of Participants Completing Treatment
Number of participants who successfully initiated and completed the intended 2-hour LUCID treatment protocol. Adherence includes documented time to placement (interval between ROC and treatment initiation) and any deviations or interruptions to the 2-hour duration (e.g., EEG placement). Adherence to the LUCID protocol will be monitored including use of the LUCID cap if the patient is deemed eligible and consented. Time to placement of the LUCID cap will be documented including the interval between the time of ROC and the time LUCID is placed and treatment is initiated. Any deviations to the standard treatment protocol duration of 2 hours will be documented. Any anticipated interruptions (e.g., EEG electrode placement), and unanticipated events will be documented, and details described.
Time frame: 28 days
Secondary Endpoint 4: Acceptability
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Acceptability will be assessed by a brief survey with the bedside nurse after the LUCID treatment; and with the LAR at the time of completion of the day 7 outcome measures.
Time frame: 7 days
Secondary Endpoint 5: Vineland Adaptive Behavior Scales Third Edition
Vineland Adaptive Behavior Scales Third Edition (VABS-3) will be used to obtain a standardized quantifiable measure of neurobehavioral function in survivors.15 VABS-3 uses LAR report to provide age corrected scores in three core domains (communication, daily living, socialization) with a composite score of these domains. Earlier versions of the Vineland (VABS-2) have been used to study infants and children who have experienced a cardiac arrest where death was assigned a score of zero, as will be done in this study.16,17 VABS-3 will be administered as a semi-structured interview with the LAR either in-person or remotely over the telephone or virtual meeting. The time required to complete the subset of questions intended for an infant \< 1 year of age is less than 20 minutes. Baseline VABS-3 information will be collected at the time of participant enrollment (prior to IHCA). VABS-3 will also be collected at day 28 post-ROC (or PICU/CICU discharge, whichever occurs first) and 3 mo
Time frame: 3 months
Secondary Endpoint 6: Pediatric Resuscitation after Cardiac Arrest Scale
Pediatric Resuscitation after Cardiac Arrest (PRCA) scale will be used to obtain a standardized age appropriate neurologic examination. Neurologic function will be scored (0, normal to 3, severe impairment) in 6 domains. The sensorimotor domain is scored independently for each side of the body. The five other scored domains include other non lateralizing sensorimotor function (encompassing cranial nerve deficits, movement/tone disorder, global delays), language production, language comprehension, cognition, and behavior. Total PRCA scores range from 0-21, with 0 indicating no deficits and 21 indicating maximal deficits. Scores are categorized as 0-3 (no/minimal impairment), 4-7 (mild impairment), 8-11 (moderate impairment), 12-16 (severe impairment), and 17-21 (profound impairment). PRCA exam will be performed near the time of enrollment (prior to IHCA), within the 24-hour period post-ROC, day 28 post-ROC (or PICU/CICU discharge, whichever occurs first), and 3 months.
Time frame: 3 months
Secondary Endpoint 7: Neurological Status as Assessed by Murray's EEG Grading Criteria
EEG findings will be graded using Murray's criteria (for neonates) and matching criteria for older patients to assess post-arrest brain function. Evaluation includes the SCORE system for interpretation and documentation of background rhythm, interictal spikes, sleep architecture (spindles/K complexes), and seizure activity. The protocol also includes: Scalp EEG monitoring will proceed per local protocol for post-arrest care, with typical lead placement at 22-24 hours after ROS. A standard 10-20 EEG system with nine scalp electrodes (Fp1, Fp2, C3, C4, O1, O2, T3, T4, and Cz) will be used following the guidelines endorsed by the ACNS. Parameters that will be documented are background alpha rhythm; interictal spikes, abnormal interictal rhythmic activity and periodic discharges, and sleep architecture will be qualitatively assessed for sleep spindles and K complexes; electrographic seizures, or clinical seizures.
Time frame: 3 months
Secondary Endpoint 8: Incidence of Elevated Neuro-injury Biomarker Levels
Participants' plasma levels for six biomarkers (Neurofilament light chain, GFAP, UCH-L1, NSE, S100b, and tau) are measured 24 (+ 4) hours and 7 days after Return of Circulation (ROC). Levels are compared against established age-matched reference ranges for healthy infants to determine elevation. Time Frame: 24 hours (+ 4 hours) and 7 days post-ROC
Time frame: 24 hours and 7 days
Secondary Endpoint 9: Presence of Ischemic Brain Injury as Assessed by Clinical Neuroimaging (CT/MRI)
Evaluation of brain and brain stem integrity via clinically indicated CT and/or MRI scans. Radiology reports will be reviewed for findings of ischemia-reperfusion injury, including cerebral edema or infarction. This measure will report the number of participants with documented imaging evidence of brain injury during the study period. The protocol states: Computed tomography (CT) and magnetic resonance imaging (MRI) scans of brain and brain stem, and corresponding radiology reports, that are obtained for clinical purposes at any time during the 3-month study period will be collected.
Time frame: 3 months