Feasibility of Use of Indocyanine Green in Pediatric Colorectal Surgery

NCT04904081 | Recruiting Phase 3

• 1 other identifier: #202103
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Hirschsprung's Disease (HD) and anorectal malformations (ARM) are both paediatric diseases of the colon and rectum. Both of these conditions require surgery in order to correct them, frequently needing sections of the bowel to be removed. Some complications of removing parts of the bowel include forming a stricture (a narrowing of the place where the bowel is reattached), and leak from the join. These can be devastating complications, and can significantly impact a patient's quality of life. Indocyanine green (ICG) is a medication that binds to blood vessels and can be visualized using special cameras in the operating room. Once it binds, it "lights up" green on this equipment. This lends the advantage of being able to better see which parts of the bowel get good blood flow. The theory is that good blood flow can reduce the risks of previously mentioned complications. This has been shown to be true in a variety of bowel surgeries in adults. ICG has also been shown to be safe in children. Given that HD and ARM are both relatively rare conditions (\~1/5000 live births), research in this area needs to be strategic. The investigators want to ensure that the investigators can recruit enough patients to the study using this protocol such that if this were to be scaled up to a multi-centre trial in the future, the investigators could demonstrate feasibility. The investigators will collect data both on the feasibility of recruitment as the primary outcome and secondary outcomes including stricture, leak, length of stay in hospital, and return to hospital.

Conditions

Hirschsprung Disease; Anorectal Malformations

Outcome Measures

Primary Outcomes (4)

• The number of eligible paediatric patients treated for HD or ARM at the local institute that would qualify for participation in this trial.

  The number of eligible patients that are treated for HD and ARM at this institution regardless of if they enrolled in the study or not.

  12 months

• The number of eligible paediatric patients treated for HD or ARM that enroll in this study during the recruitment period of this study.

  The number of eligible patient who enroll in this study during the recruitment period compared to the total number of eligible patient.

  12 months

• The number of eligible paediatric patients treated for HD or ARM that enroll in this study and attend al required study visits.

  This outcome will capture the number of patient who are enrolled in the study and present to the hospital on the day of surgery, and for each follow-up visit where data will be collected.

  12 months

• The number of eligible paediatric patients treated for HD or ARM that enrolled in this study but are lost to attrition/drop-out during the study

  This outcome captures the number of patient who enroll in the study but do not complete the study (including follow-up visits) or withdraw from the study before undergoing surgery.

  12 months

Secondary Outcomes (8)

• If the use of ICG alters the intraoperative management of the patient, resulting in the surgeon resecting a longer segment of bowel.

  5 hours

• If the use of ICG alters the length of operative time between ICG and control group

  5 hours

• If the use of ICG alters the length of stay in hospital between ICG and control group

  2 weeks

• Rates of anastomotic dehiscence

  Up to 6 months post surgery

• Rates of anal stricture (mild) not requiring anal dilatations

  Up to 6 months post surgery

Other Outcomes (4)

• Adverse reaction to ICG resulting in anaphylaxis

  Up to 2 weeks post-op

• Adverse reaction to ICG resulting in urticarial reactions

  Up to 2 weeks post-op

• Adverse reaction to ICG resulting in drug interactions

  Up to 2 weeks post-op

Study Arms (2)

Treatment Arm (Indocyanine Green [ICG])

EXPERIMENTAL

The ICG group will involve the patient receiving standard care for either HD or ARM, in addition to 1.25mg (maximum dose less than 2mg/kg body weight) of ICG intraoperatively, administered intravenously. ICG will be administered by a member of the anesthesia team when directed by the surgeon (research team member).

Drug: Indocyanine green

Control Arm (Standard Care)

NO INTERVENTION

The Standard Care group will have no change to the medical and surgical care they receive while in the hospital. The surgeon will perform the surgery as they normally would outside of this study. This involves a laparoscopic-assisted transanal pullthrough surgery.

Interventions

Indocyanine green DRUG

The ICG group will involve the patient receiving standard care for either HD or ARM, in addition to 1.25mg (maximum dose less than 2mg/kg body weight) of ICG intraoperatively, administered intravenously. ICG will be administered by a member of the anesthesia team when directed by the surgeon (research team member).

Treatment Arm (Indocyanine Green [ICG])

Eligibility Criteria

• Age: 1 Month - 7 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• All patients with Hirschsprung's disease or anorectal malformations, diagnosed by:
• Clinical evaluation and physical examination
• Radiologic studies including abdominal x-rays and/or contrast enemas
• Pathologic diagnosis after rectal biopsies (HD only)
• Patients greater than one-month of age to 7 years of age at the time of surgery
• Patient requires surgical management for their diagnosis
• Patient/Substitute decision maker (SDM) able to read/write/understand English

You may not qualify if:

• Those patients and SDM unwilling to provide consent
• Pregnant and/or women who are breast feeding
• Patients with a known iodine allergy

Sponsors & Collaborators

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: lead

Study Sites (1)

Children's Hospital, London Health Sciences Centre

London, Ontario, N6A5W9, Canada

RECRUITING

Related Publications (21)

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  PMID: 20307847 BACKGROUND

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• Tang ST, Wang GB, Cao GQ, Wang Y, Mao YZ, Li SW, Li S, Yang Y, Yang J, Yang L. 10 years of experience with laparoscopic-assisted endorectal Soave pull-through procedure for Hirschsprung's disease in China. J Laparoendosc Adv Surg Tech A. 2012 Apr;22(3):280-4. doi: 10.1089/lap.2011.0081.

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• Lu C, Hou G, Liu C, Geng Q, Xu X, Zhang J, Chen H, Tang W. Single-stage transanal endorectal pull-through procedure for correction of Hirschsprung disease in neonates and nonneonates: A multicenter study. J Pediatr Surg. 2017 Jul;52(7):1102-1107. doi: 10.1016/j.jpedsurg.2017.01.061. Epub 2017 Feb 2.

  PMID: 28185631 BACKGROUND

• Engum SA, Grosfeld JL. Long-term results of treatment of Hirschsprung's disease. Semin Pediatr Surg. 2004 Nov;13(4):273-85. doi: 10.1053/j.sempedsurg.2004.10.015.

  PMID: 15660321 BACKGROUND

• Ryu S, Suwa K, Kitagawa T, Aizawa M, Ushigome T, Okamoto T, Eto K, Yanaga K. Real-Time Fluorescence Vessel Navigation Using Indocyanine Green During Laparoscopic Colorectal Cancer Surgery. Anticancer Res. 2019 Jun;39(6):3009-3013. doi: 10.21873/anticanres.13433.

  PMID: 31177142 BACKGROUND

• Elsaied A, Aly K, Thabet W, Magdy A. Two-stage repair of low anorectal malformations in girls: is it truly a setback?. Annals of Pediatric Surgery. 2013;9(2):69-73.

  BACKGROUND

• Peng CH, Chen YJ, Pang WB, Zhang TC, Wang ZM, Wu DY, Wang K. STROBE-anastomotic leakage after pull-through procedure for Hirschsprung disease. Medicine (Baltimore). 2018 Nov;97(46):e13140. doi: 10.1097/MD.0000000000013140.

  PMID: 30431584 BACKGROUND

• Tofft L, Salo M, Arnbjornsson E, Stenstrom P. Wound Dehiscence after Posterior Sagittal Anorectoplasty in Children with Anorectal Malformations. Biomed Res Int. 2018 Nov 11;2018:2930783. doi: 10.1155/2018/2930783. eCollection 2018.

  PMID: 30534556 BACKGROUND

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  PMID: 29471617 BACKGROUND

• Alander JT, Kaartinen I, Laakso A, Patila T, Spillmann T, Tuchin VV, Venermo M, Valisuo P. A review of indocyanine green fluorescent imaging in surgery. Int J Biomed Imaging. 2012;2012:940585. doi: 10.1155/2012/940585. Epub 2012 Apr 22.

  PMID: 22577366 BACKGROUND

• Wada T, Kawada K, Takahashi R, Yoshitomi M, Hida K, Hasegawa S, Sakai Y. ICG fluorescence imaging for quantitative evaluation of colonic perfusion in laparoscopic colorectal surgery. Surg Endosc. 2017 Oct;31(10):4184-4193. doi: 10.1007/s00464-017-5475-3. Epub 2017 Mar 9.

  PMID: 28281123 BACKGROUND

• Esposito C, Del Conte F, Cerulo M, Gargiulo F, Izzo S, Esposito G, Spagnuolo MI, Escolino M. Clinical application and technical standardization of indocyanine green (ICG) fluorescence imaging in pediatric minimally invasive surgery. Pediatr Surg Int. 2019 Oct;35(10):1043-1050. doi: 10.1007/s00383-019-04519-9. Epub 2019 Jul 4.

  PMID: 31273452 BACKGROUND

• Esposito C, Settimi A, Del Conte F, Cerulo M, Coppola V, Farina A, Crocetto F, Ricciardi E, Esposito G, Escolino M. Image-Guided Pediatric Surgery Using Indocyanine Green (ICG) Fluorescence in Laparoscopic and Robotic Surgery. Front Pediatr. 2020 Jun 17;8:314. doi: 10.3389/fped.2020.00314. eCollection 2020.

  PMID: 32626676 BACKGROUND

• Rentea RM, Halleran DR, Ahmad H, Sanchez AV, Gasior AC, McCracken K, Hewitt GD, Alexander V, Smith C, Weaver L, Wood RJ, Levitt MA. Preliminary Use of Indocyanine Green Fluorescence Angiography and Value in Predicting the Vascular Supply of Tissues Needed to Perform Cloacal, Anorectal Malformation, and Hirschsprung Reconstructions. Eur J Pediatr Surg. 2020 Dec;30(6):505-511. doi: 10.1055/s-0039-1700548. Epub 2019 Dec 13.

  PMID: 31858494 BACKGROUND

• Goldstein SD, Heaton TE, Bondoc A, Dasgupta R, Abdelhafeez A, Davidoff AM, Lautz TB. Evolving applications of fluorescence guided surgery in pediatric surgical oncology: A practical guide for surgeons. J Pediatr Surg. 2021 Feb;56(2):215-223. doi: 10.1016/j.jpedsurg.2020.10.013. Epub 2020 Oct 19.

  PMID: 33189300 BACKGROUND

• Foppa C, Denoya PI, Tarta C, Bergamaschi R. Indocyanine green fluorescent dye during bowel surgery: are the blood supply "guessing days" over? Tech Coloproctol. 2014 Aug;18(8):753-8. doi: 10.1007/s10151-014-1130-3. Epub 2014 Feb 21.

  PMID: 24558047 BACKGROUND

• Emran M, Wayne C, Koehler SM, Almond PS, Patel H. Intraoperative ICG-NIR Fluorescence Angiography Visualization of Intestinal Perfusion in Primary Pull-Through for Hirschsprung Disease. International Journal of Medical and Health Sciences. 2020 Nov 1;14(12):408-11

  BACKGROUND

• Balamurugan S, Agrawal A, Kato Y, Sano H. Intra operative indocyanine green video-angiography in cerebrovascular surgery: An overview with review of literature. Asian J Neurosurg. 2011 Jul;6(2):88-93. doi: 10.4103/1793-5482.92168.

  PMID: 22347330 BACKGROUND

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  PMID: 11373197 BACKGROUND

• Hope-Ross M, Yannuzzi LA, Gragoudas ES, Guyer DR, Slakter JS, Sorenson JA, Krupsky S, Orlock DA, Puliafito CA. Adverse reactions due to indocyanine green. Ophthalmology. 1994 Mar;101(3):529-33. doi: 10.1016/s0161-6420(94)31303-0.

  PMID: 8127574 BACKGROUND

MeSH Terms

Conditions

Hirschsprung Disease; Anorectal Malformations

Interventions

Indocyanine Green

Condition Hierarchy (Ancestors)

Digestive System Abnormalities; Digestive System Diseases; Megacolon; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Andreana Butter, MD

  Pediatric Surgeon, Children's Hospital, LHSC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jacob Davidson, MSc

CONTACT

519-685-8500; Jacob.Davidson@lhsc.on.ca

Andreana Butter, MD

CONTACT

519-685-8500; Andreana.Butter@lhsc.on.ca

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Single-blind (participants only)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2021
• First Posted: May 27, 2021
• Study Start: June 16, 2021
• Primary Completion: June 1, 2024
• Study Completion: July 1, 2024
• Last Updated: March 15, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)