Safety and Feasibility of Indocyanine Green Fluorescence for Intraoperative Assessment of Intestinal Perfusion in Young Infants and Neonates

Study Overview
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Brief Summary
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The goal of this clinical trial is to test the use of the SPY-PHI device for the purpose of ICG-mediated intestinal perfusion visualization during gastrointestinal surgery in neonates and young infants (<3 months old) undergoing surgery for NEC, atresia, SIP or malrotation. The main question[s] it aims to answer are: Is ICG-FA feasible for intraoperative use in neonates and young infants undergoing laparotomy for NEC, atresia, SIP or malrotation? Is ICG-FA is safe to use in neonates during surgery? Participants will undergo surgical care for their diseases within the standard of care. During laparotomy, the pediatric surgeon will assess bowel perfusion in two ways. First, by visual inspection (the conventional method). Second, the intestine will be analyzed with indocyanine green fluorescence angiography (ICG-FA) by means of the hand-held SPY-PHI camera. For this purpose, the patients will be administered ICG intravenously. Afterwards, the intestinal perfusion will be assessed by means of the SPY-PHI device in 5 to 10 minutes. Specifically, the feasibility and safety for use of ICG-FA in neonates undergoing laparotomy as treatment for necrotizing enterocolitis (NEC), atresia, spontaneous intestinal perforation (SIP) and malrotation will be investigated. If ICG-FA turns out to be feasible and safe for the population investigated in this study, a follow-up study will be conducted with the aim to explore the potential benefits of this technique on the postoperative outcome and intraoperative decision-making.

Detailed Description
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This study aims to investigate whether the intraoperative use of indocyanine green fluorescence angiography (ICG-FA) is feasible and safe in neonates. Feasibility is therein defined as practically possible use of ICG-FA, resulting in clear and interpretable results, with the future potential to improve clinical outcome and benefits for the patient. Specifically, the feasibility and safety for use of ICG-FA in neonates undergoing laparotomy as treatment for necrotizing enterocolitis (NEC), atresia, spontaneous intestinal perforation (SIP) and malrotation will be investigated. If ICG-FA turns out to be feasible and safe for the population investigated in this study, a follow-up study will be conducted with the aim to explore the potential benefits of this technique on the postoperative outcome and intraoperative decision-making. The primary endpoint of this study is assessing the feasibility and safety of intraoperative ICG-FA imaging in neonates undergoing laparotomy for NEC, atresia, SIP, or malrotation. The secondary endpoint of this study is postoperative comparison of the images; standard visual inspection (conventional image) with the corresponding fluorescence image. During laparotomy, first the pediatric surgeon performs the visual inspection of the predetermined areas (mid jejunum, ileum, ascending colon and sigmoid) as well as regions of interest such as ischemic lesions in NEC and malrotation with volvulus. In case of intestinal necrosis, both edges of the parts that will be resected must be marked with a suture. Second, the intestine will be analyzed using ICG-FA. This analysis will cover the predetermined areas as well as regions of interest. To this end, the ICG should be injected intravenously by the one member of the anesthetic team. This will only be done if the operating team, consisting of both the consultant surgeon and consultant pediatric anesthesiologist, consider it safe to do so. Utilizing the mobile unit with computer and camera head, the fluorescence angiography system can measure tissue perfusion. Before the start of the procedure in which the SPY-PHY camera will be used intraoperatively, the camera will be covered with sterile drapes. The pediatric surgeon will first make conventional video images with the camera of the predetermined areas and the region of interest and second, the surgeon will make images of the ICG-FA with the camera, which both will be recorded to be analyzed later. The ICG-FA images do not alter the decision on what type of surgical procedure will be performed and/or how much length of bowel will be resected. In case of a difficult decision, a second pediatric surgeon will be consulted, which is routine clinical practice in both centers anyway.

Official Title
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Indocyanine Green Fluorescence Angiography Mediated Assessment of Gastro-Intestinal Perfusion in Neonates

Conditions
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NEC, Atresia, Malrotation, Intestinal Perforation

Intervention / Treatment
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* Device: Perfusion assessment by means of the SPY-PHI camera


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent is obtained by both patient's parents or legal guardians (as applicable); Patient is a neonate (< 1 month of age) or young infant (<3 months of age); Patient is suffering from necrotizing enterocolitis, atresia, malrotation or spontaneous intestinal perforation; Patient requires laparotomy for management of the disease. Exclusion Criteria: Patient is suffering from clinically significant (treatment necessary) hyperbilirubinemia; Patient is suffering from thyroid or liver disease; Patient is allergic to the active substance indocyanine green or sodium iodide or iodine; Patient has abdominal wall defects; Patient can be treated non-surgically; During the preoperative multidisciplinary meeting with the team, including the pediatric anesthetist, patient is deemed not stable enough hemodynamically to perform the ICG-FU measurements Patient is assessed unstable by operating team intraoperatively.

Ages Eligible for Study
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Maximum Age: 3 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intraoperative perfusion assessment using ICG-FA<br>Surgical procedure within standard of care. Intraoperatively, the vitality of the bowel will be assessed visually (the conventional method). Afterwards, participants will be administered indocyanine green intravenously. | Device: Perfusion assessment by means of the SPY-PHI camera<br>* Minutes after injection of ICG, the intestinal perfusion can and will be assessed using the SPY-PHI camera by Stryker Endoscopy. The operative plan will not be changed based on the results of the perfusion assessment. Images will be recorded and evaluated postoperatively.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of ICG-FA for intraoperative assessment of intestinal perfusion | a. Possibility for the researchers to assess intestinal perfusion based on the intraoperative ICG-FA images (clarity: yes/no); | 10 minutes intraoperatively (recording) | 
| Feasibility of ICG-FA for intraoperative assessment of intestinal perfusion | b. Possibility for the researchers to point out a specific location for resection of the bowel based on visualization of perfusion in the ICG-FA images (interpretability: yes/no); | 10 minutes intraoperatively (recording) | 
| Feasibility of ICG-FA for intraoperative assessment of intestinal perfusion | c. Comparison of the number of procedures in which it was a priori possible to perform ICG-FA imaging and the number of procedures in which the device was eventually used intraoperatively (applicability); | 10 minutes intraoperatively (recording) | 
| Feasibility of ICG-FA for intraoperative assessment of intestinal perfusion | d. Interference with intraoperative Near Infrared Spectroscopy (NIRS) brain monitoring (compatibility: brain monitoring not interfered with/possible despite interference/impossible due to interference); | 10 minutes intraoperatively (recording) | 
| Safety of intraoperative ICG-FA in gastrointestinal surgery for young infants and neonates | a. Number of complications directly related to use of the device or extension of operative time for ICG-FA imaging, occurring within 24 hours after surgery in the patients involved in this study; | 24 hours | 
| Safety of intraoperative ICG-FA in gastrointestinal surgery for young infants and neonates | b. Measurement of the prolonged OR time associated with intraoperative ICG-FA in minutes; | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of conventional and ICG-FA mediated assessment | a. Comparing whether the perfusion assessment of ICG-FA can provide more certainty on the perfusion status of intestinal sections than conventional visual assessment (by comparing ICG-FA images with normal view images) in order to identify whether ICG-FA, if applied for decision-making, would have confirmed or altered intraoperative decision making. | Through study completion, on average within 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neonate, Infant, ICG, Fluorescence, Image-guided surgery, Pediatric Surgery, Intestinal perfusion, Anastomosis, Safety, Feasibility, Bowel ischemia