Hirschsprung DiseasePhase 3NCT04904081
Feasibility of Use of Indocyanine Green in Pediatric Colorectal Surgery
A Phase 3 study testing Indocyanine green in people with Hirschsprung Disease and Anorectal Malformations, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 month to 7 years
- Conditions the study is for
- Hirschsprung Disease, Anorectal Malformations
- What is being tested?
- Indocyanine green
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteCanada
- Study dates
- 16 Jun 2021to Jul 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 month to 7 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- Those patients and SDM unwilling to provide consent
- Pregnant and/or women who are breast feeding
- Patients with a known iodine allergy
Trial locations and contacts
1 site in 1 country.
Canada1 site, 1 recruiting
- Recruiting
Children's Hospital, London Health Sciences Centre
London, Ontario, N6A5W9
Jacob Davidson, MSc, 519-685-8500 ext. 53298, Jacob.Davidson@lhsc.on.ca
Andreana Butter, MD
About this study
Official title: The Use of Indocyanine Green Angiography in Pediatric Colorectal Surgery: A Feasibility Randomized Controlled Trial
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.
Read the detailed description
Pediatric colorectal conditions, such as Hirschsprung's disease (HD) and anorectal malformations (ARM), result in significant disease burden in pediatric populations in Canada. Both conditions are present in approximately 1 in 5000 live births. Surgical correction of these anomalies is typically performed in Children's Hospitals in Canada. Postoperative complications, such as anal stricture and anal stenosis, have been reported to occur in 2-35% and 2-10%, after posterior-sagittal anorectoplasty (PSARP) and laparoscopic-assisted pull through for ARM and HD, respectively. In addition, anastomotic leaks and dehiscence are life-threatening, and should be avoided at all costs. The literature estimates the rate of anastomotic leak in HD to be approximately 2%, but have been reported in as high as 10% in neonatal patients. Wound dehiscence post ARM repair has been estimated as high as 30-40%. It is hypothesized that the above post-operative complications occur due to compromised vascular supply to the bowel undergoing coloanal anastomosis at the time of pull-through.
Traditionally, surgeons evaluate bowel viability with tactile and visual means, including discoloration, bleeding from the cut edge, and peristalsis after resection. With the push towards minimally invasive surgeries over recent decades, the adoption of surgical technology which can replace open or tactile assessments is necessary. One such example is the use of indocyanine green (ICG) for assessing bowel perfusion in laparoscopic surgery. ICG is a nontoxic, nonimmunogenic, water-soluble intravascular imagine agent. It has a short half-life (approximately 3-5 minutes) and when injected intravenously, it binds to plasma proteins and proteins in the lymph fluid keeping it in the intravascular compartment. ICG absorbs light in the near-infrared region (806 nm) and emits fluorescent light at 830 nm. ICG was approved by the Food and Drug Administration (FDA, New Drug Application [NDA] 211580 505(b)(2) via fda.gov) for use in adults in the late 1950s and has since been approved for use in adults by Health Canada.
A review article published in 2012 identified over 200 manuscripts describing safe and reliable use of ICG in surgical procedures in adults. More specifically, qualitative analysis of bowel perfusion enhanced by ICG in colorectal cancer patients has been shown to reduce rates of anastomotic leak by approximately 4%. Practically speaking, the use of ICG florescence technique can be useful in identifying clinical vascular anatomy in colorectal surgery, both via open and laparoscopic approaches, allowing surgeons to better preserve important structures.
Several studies have shown that ICG is safe among pediatric populations, with utility demonstrated in cases of difficult cholecystectomy, hydrocele repairs, and localizing metastatic disease. As such, the FDA has approved the use of ICG in paediatric patients. Research studies from the US, have examined the intravenous application of ICG for more than 60 years in adults and children with few reported adverse effects. However, Health Canada has not reported on the safety and efficacy of ICG and does not authorize an indication for its use.
To our knowledge, there have only been two studies that have looked at intraoperative ICG to visualize intestinal perfusion for primary pull-through in Hirschsprung Disease and anorectal malformation repair patients and both were retrospective studies. A previous study included eight patients, diagnosed with HD undergoing transanal, open or laparoscopically-assisted pull-through procedures after biopsy confirmation of aganglionosis. Patients were given a dose of 1.25mg (<2 mg/kg) of ICG intraoperatively in the operating room. In five of the eight patients, the level of the bowel transection was changed based on the ICG visualization. In the other three patients, ICG confirmed the surgeon's assessment of where the resection should occur. There were no intraoperative complications or complications noted at two-week, one-month, and three-month follow-up visits. Further no leaks, incontinence, or strictures were noted at any of these follow-up visits. Another study 16 included 13 patients in total, nine undergoing cloacal reconstruction, four with HD and one with an ARM. ICG was used to predict the vascular supply during the reconstruction procedure and patients were given an intravenous dose of ICG between 0.1 to 0.3mg/kg in the operating room. There were no intraoperative adverse events or side effects from the ICG. ICG changed the operative plan in four out of 13 cases (31%), one of those four cases being a pull-through for HD. For this HD case, ICG resulted in the detection of 10cm of non-viable colon which may not have previously been detected. Although the level of evidence is limited by study design and small sample sizes, these studies help to provide rationale for the continued study of ICG use in paediatric patients.
Despite the results from these studies, future work is needed before he investigators can determine the effectiveness of ICG in reducing rates of post PSARP and pull-through complications. Practically speaking, the main inhibitors to widespread adoption of ICG in these surgeries is the cost of the technology, and lack of data to support that it truly reduces the rates of complications associated with these surgeries. Our research team, looks to be the first group to explore the feasibility of using ICG in a paediatric population with Hirschsprung's Disease and anorectal malformations. The investigators hope that the results from the study will help to initiate future multicenter, randomized controlled trials to provide high level evidence to support the use of ICG in colorectal surgeries in paediatric patients.
- Conditions
- Hirschsprung Disease, Anorectal Malformations
- Being tested
- Indocyanine green
- Medical subject headings
- Hirschsprung Disease, Anorectal Malformations
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Indocyanine greenDrug
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).
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
This will be difference in where the surgeon would resect the bowel based on their clinical judgement and where the blood perfusion (indicated by ICG) suggests the resection should be made. This will be measure in millimeters.
Measured: 5 hours
If the use of ICG alters the length of operative time between ICG and control group
This will be measured by comparing the length of operation for similar cases/diagnoses that are randomized to each study arm. This will be measured in minutes
Measured: 5 hours
If the use of ICG alters the length of stay in hospital between ICG and control group
This outcome will be tracked by measuring the length of hospital stay post-surgery for each patient enrolled in the study. This will be recorded in days.
Measured: 2 weeks
Rates of anastomotic dehiscence
This will be monitored as per standard surgical aftercare and monitoring by the surgeon. This data will be collected from the assessment of the surgeon and the patient's medical chart.
Measured: Up to 6 months post surgery
Rates of anal stricture (mild) not requiring anal dilatations
This will be monitored as per standard surgical aftercare and monitoring by the surgeon. This data will be collected from the assessment of the surgeon and the patient's medical chart.
Measured: Up to 6 months post surgery
Rate of anal stricture (moderate or severe) requiring anal dilatations
This will be monitored as per standard surgical aftercare and monitoring by the surgeon. This data will be collected from the assessment of the surgeon and the patient's medical chart.
Measured: Up to 6 months post surgery
Rate of hospital readmission in the first 30 days postoperatively
This will be monitored as per standard surgical aftercare and monitoring by the surgeon. This data will be collected from the patient's medical chart.
Measured: Up to 6 months post surgery
Rate of an additional related procedure under general anaesthesia (i.e. return to the operating room or interventional radiology)
This will be monitored as per standard surgical aftercare and monitoring by the surgeon. This data will be collected from the assessment of the surgeon and the patient's medical chart.
Measured: Up to 6 months post surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 May 2021
- Study start16 Jun 2021
- Primary completionJun 2024 (estimated)
- Study completionJul 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (21)Papers the sponsor has linked to this study.
- Other trials for Hirschsprung DiseaseStudies of the same condition, open and under way.
- More trials run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Andreana Butter, MD, Principal investigator, Pediatric Surgeon, Children's Hospital, LHSC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04904081
- Sponsor's protocol ID
- #202103
- Status last verified
- Mar 2024
- First submitted
- 14 May 2021
- Last updated
- 15 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: We will not be sharing individual participant data (IPD)
Publications
Mundt E, Bates MD. Genetics of Hirschsprung disease and anorectal malformations. Semin Pediatr Surg. 2010 May;19(2):107-17. doi: 10.1053/j.sempedsurg.2009.11.015.
PubMed 20307847Kudszus S, Roesel C, Schachtrupp A, Hoer JJ. Intraoperative laser fluorescence angiography in colorectal surgery: a noninvasive analysis to reduce the rate of anastomotic leakage. Langenbecks Arch Surg. 2010 Nov;395(8):1025-30. doi: 10.1007/s00423-010-0699-x. Epub 2010 Aug 12.
PubMed 20700603Tang 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.
PubMed 22449115Lu 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.
PubMed 28185631Engum 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.
PubMed 15660321Ryu 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.
PubMed 31177142Elsaied 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.
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.
PubMed 30431584Tofft 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.
PubMed 30534556Cassinotti E, Costa S, DE Pascale S, Oreggia B, Palazzini G, Boni L. How to reduce surgical complications in rectal cancer surgery using fluorescence techniques. Minerva Chir. 2018 Apr;73(2):210-216. doi: 10.23736/S0026-4733.18.07632-0. Epub 2018 Feb 21.
PubMed 29471617Alander 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.
PubMed 22577366Wada 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.
PubMed 28281123Esposito 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.
PubMed 31273452Esposito 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.
PubMed 32626676Rentea 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.
PubMed 31858494
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Use of Indocyanine Green Angiography in Pediatric Colorectal Surgery: A Feasibility Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT04904081
- Acronym / sponsor ID
- #202103
- Conditions
- Hirschsprung Disease, Anorectal Malformations
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sUniversity, hospital or other
- Study start
- 16 Jun 2021 (actual)
- Primary completion
- Jun 2024 (estimated)
- Study completion
- Jul 2024 (estimated)
- First posted
- 27 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Pediatric colorectal conditions, such as Hirschsprung's disease (HD) and anorectal malformations (ARM), result in significant disease burden in pediatric populations in Canada. Both conditions are present in approximately 1 in 5000 live births. Surgical correction of these anomalies is typically performed in Children's Hospitals in Canada. Postoperative complications, such as anal stricture and anal stenosis, have been reported to occur in 2-35% and 2-10%, after posterior-sagittal anorectoplasty (PSARP) and laparoscopic-assisted pull through for ARM and HD, respectively. In addition, anastomotic leaks and dehiscence are life-threatening, and should be avoided at all costs. The literature estimates the rate of anastomotic leak in HD to be approximately 2%, but have been reported in as high as 10% in neonatal patients. Wound dehiscence post ARM repair has been estimated as high as 30-40%. It is hypothesized that the above post-operative complications occur due to compromised vascular supply to the bowel undergoing coloanal anastomosis at the time of pull-through.
Traditionally, surgeons evaluate bowel viability with tactile and visual means, including discoloration, bleeding from the cut edge, and peristalsis after resection. With the push towards minimally invasive surgeries over recent decades, the adoption of surgical technology which can replace open or tactile assessments is necessary. One such example is the use of indocyanine green (ICG) for assessing bowel perfusion in laparoscopic surgery. ICG is a nontoxic, nonimmunogenic, water-soluble intravascular imagine agent. It has a short half-life (approximately 3-5 minutes) and when injected intravenously, it binds to plasma proteins and proteins in the lymph fluid keeping it in the intravascular compartment. ICG absorbs light in the near-infrared region (806 nm) and emits fluorescent light at 830 nm. ICG was approved by the Food and Drug Administration (FDA, New Drug Application [NDA] 211580 505(b)(2) via fda.gov) for use in adults in the late 1950s and has since been approved for use in adults by Health Canada.
A review article published in 2012 identified over 200 manuscripts describing safe and reliable use of ICG in surgical procedures in adults. More specifically, qualitative analysis of bowel perfusion enhanced by ICG in colorectal cancer patients has been shown to reduce rates of anastomotic leak by approximately 4%. Practically speaking, the use of ICG florescence technique can be useful in identifying clinical vascular anatomy in colorectal surgery, both via open and laparoscopic approaches, allowing surgeons to better preserve important structures.
Several studies have shown that ICG is safe among pediatric populations, with utility demonstrated in cases of difficult cholecystectomy, hydrocele repairs, and localizing metastatic disease. As such, the FDA has approved the use of ICG in paediatric patients. Research studies from the US, have examined the intravenous application of ICG for more than 60 years in adults and children with few reported adverse effects. However, Health Canada has not reported on the safety and efficacy of ICG and does not authorize an indication for its use.
To our knowledge, there have only been two studies that have looked at intraoperative ICG to visualize intestinal perfusion for primary pull-through in Hirschsprung Disease and anorectal malformation repair patients and both were retrospective studies. A previous study included eight patients, diagnosed with HD undergoing transanal, open or laparoscopically-assisted pull-through procedures after biopsy confirmation of aganglionosis. Patients were given a dose of 1.25mg (<2 mg/kg) of ICG intraoperatively in the operating room. In five of the eight patients, the level of the bowel transection was changed based on the ICG visualization. In the other three patients, ICG confirmed the surgeon's assessment of where the resection should occur. There were no intraoperative complications or complications noted at two-week, one-month, and three-month follow-up visits. Further no leaks, incontinence, or strictures were noted at any of these follow-up visits. Another study 16 included 13 patients in total, nine undergoing cloacal reconstruction, four with HD and one with an ARM. ICG was used to predict the vascular supply during the reconstruction procedure and patients were given an intravenous dose of ICG between 0.1 to 0.3mg/kg in the operating room. There were no intraoperative adverse events or side effects from the ICG. ICG changed the operative plan in four out of 13 cases (31%), one of those four cases being a pull-through for HD. For this HD case, ICG resulted in the detection of 10cm of non-viable colon which may not have previously been detected. Although the level of evidence is limited by study design and small sample sizes, these studies help to provide rationale for the continued study of ICG use in paediatric patients.
Despite the results from these studies, future work is needed before he investigators can determine the effectiveness of ICG in reducing rates of post PSARP and pull-through complications. Practically speaking, the main inhibitors to widespread adoption of ICG in these surgeries is the cost of the technology, and lack of data to support that it truly reduces the rates of complications associated with these surgeries. Our research team, looks to be the first group to explore the feasibility of using ICG in a paediatric population with Hirschsprung's Disease and anorectal malformations. The investigators hope that the results from the study will help to initiate future multicenter, randomized controlled trials to provide high level evidence to support the use of ICG in colorectal surgeries in paediatric patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm (Indocyanine Green [ICG]) | Experimental | Drug: Indocyanine greenThe 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). |
| 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. |
Who may qualify
- Ages
- 1 month to 7 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- All patients with Hirschsprung's disease or anorectal malformations, diagnosed by:
- 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
Key exclusion criteria (3 listed)
- Those patients and SDM unwilling to provide consent
- Pregnant and/or women who are breast feeding
- Patients with a known iodine allergy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Indocyanine greenThe 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 | Treatment Arm (Indocyanine Green [ICG]) |
Primary outcome
The number of eligible paediatric patients treated for HD or ARM at the local institute that would qualify for participation in this trial.
Time frame: 12 months
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.
The number of eligible paediatric patients treated for HD or ARM that enroll in this study during the recruitment period of this study.
Time frame: 12 months
The number of eligible patient who enroll in this study during the recruitment period compared to the total number of eligible patient.
The number of eligible paediatric patients treated for HD or ARM that enroll in this study and attend al required study visits.
Time frame: 12 months
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.
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
Time frame: 12 months
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.
8 secondary outcomes
If the use of ICG alters the intraoperative management of the patient, resulting in the surgeon resecting a longer segment of bowel.
Time frame: 5 hours
If the use of ICG alters the length of operative time between ICG and control group
Time frame: 5 hours
If the use of ICG alters the length of stay in hospital between ICG and control group
Time frame: 2 weeks
Rates of anastomotic dehiscence
Time frame: Up to 6 months post surgery
Rates of anal stricture (mild) not requiring anal dilatations
Time frame: Up to 6 months post surgery
Rate of anal stricture (moderate or severe) requiring anal dilatations
Time frame: Up to 6 months post surgery
Rate of hospital readmission in the first 30 days postoperatively
Time frame: Up to 6 months post surgery
Rate of an additional related procedure under general anaesthesia (i.e. return to the operating room or interventional radiology)
Time frame: Up to 6 months post surgery
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2024.
- Background: PubMed 20307847Mundt E, Bates MD. Genetics of Hirschsprung disease and anorectal malformations. Semin Pediatr Surg. 2010 May;19(2):107-17. doi: 10.1053/j.sempedsurg.2009.11.015.
- Background: PubMed 20700603Kudszus S, Roesel C, Schachtrupp A, Hoer JJ. Intraoperative laser fluorescence angiography in colorectal surgery: a noninvasive analysis to reduce the rate of anastomotic leakage. Langenbecks Arch Surg. 2010 Nov;395(8):1025-30. doi: 10.1007/s00423-010-0699-x. Epub 2010 Aug 12.
- Background: PubMed 22449115Tang 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.
- Background: PubMed 28185631Lu 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.
- Background: PubMed 15660321Engum 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.
- Background: PubMed 31177142Ryu 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.
- BackgroundElsaied 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: PubMed 30431584Peng 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.
- Background: PubMed 30534556Tofft 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.
- Background: PubMed 29471617Cassinotti E, Costa S, DE Pascale S, Oreggia B, Palazzini G, Boni L. How to reduce surgical complications in rectal cancer surgery using fluorescence techniques. Minerva Chir. 2018 Apr;73(2):210-216. doi: 10.23736/S0026-4733.18.07632-0. Epub 2018 Feb 21.
- Background: PubMed 22577366Alander 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.
- Background: PubMed 28281123Wada 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.
- Individual participant dataSharing planned: No. We will not be sharing individual participant data (IPD)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andreana Butter, MD principal investigator
Pediatric Surgeon, Children's Hospital, LHSC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Indocyanine green in people with Hirschsprung Disease and Anorectal Malformations, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jacob Davidson, MSc (519-685-8500 ext. 53298, Jacob.Davidson@lhsc.on.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The number of eligible paediatric patients treated for HD or ARM at the local institute that would qualify for participation in this trial. (time frame: 12 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04904081, which also lists 21 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2024.