IntAct- IFA to prevent anastomotic leak in rectal cancer surgery

ISRCTN	ISRCTN13334746
DOI	https://doi.org/10.1186/ISRCTN13334746
Secondary identifying numbers	34216

Submission date: 10/04/2017
Registration date: 02/05/2017
Last edited: 26/02/2025

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-study-looking-to-reduce-a-serious-side-effect-of-rectal-cancer-surgery-intact

Contact information

Ms Julie Croft
Public

Clinical Trials Research Unit
Leeds Institute of Clinical Trials Research
University of Leeds
Leeds
LS2 9JT
United Kingdom

ORCID ID	0000-0001-7586-3394
Phone	+44 113 343 8394
Email	j.croft@leeds.ac.uk

Study information

Study design	Randomised; Interventional; Design type: Treatment, Prevention, Imaging, Surgery
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details to request a patient information sheet
Scientific title	IntAct: Intraoperative Fluorescence Angiography to Prevent Anastomotic Leak in Rectal Cancer Surgery
Study acronym	IntAct
Study objectives	The aim of this study is to evaluate whether intraoperative fluorescent angiography (IFA) is able to decrease anastomotic leak (AL) rate in patients undergoing surgery for rectal cancer.
Ethics approval(s)	North West - Preston Research Ethics Committee, 20/04/2017, ref: 17/NW/0193
Health condition(s) or problem(s) studied	Colorectal cancer
Intervention	Current interventions as of 19/02/2021: 880 participants will be randomised prior to surgery, on a 1:1 basis, to either surgery with IFA or surgery without IFA using minimisation (incorporating a random element) and stratified by surgeon, gender, ASA grade, T-stage, neo-adjuvant therapy, and tumour position. Participants will receive an anterior resection either with or without IFA (intraoperative fluorescence angiography) depending on their randomised allocation: Surgery with no IFA: The anterior resection (high or low) will be performed according to the surgeon’s usual technique, using either a laparoscopic or robotic approach, with white light assessment of bowel perfusion. The specifics of each operation will be at the discretion of the operating surgeon. Surgery with IFA: The anterior resection (high or low) will be performed according to the surgeon’s usual technique, using either a laparoscopic or robotic approach. ICG (Indocyanine Green) will be administered intravenously at two points during the operation for perfusion assessment using near-infrared laparoscopy. A third dose of ICG will be permitted (e.g. extracorporeal assessment, or immediately prior to anastomosis) should the surgeon feel this to be beneficial. The specifics of each operation, including the decision to make a change to the planned anastomosis following IFA assessment, will be at the discretion of the operating surgeon. All patients will be followed up until 90 days post-operation. Patients will be seen in clinic at 30 days and 90 days post operation, and a rectal contrast enema scan will be performed at 4-6 weeks post operation. Patients will complete quality of life and health resource use questionnaires at baseline, 30 and 90 days post operation. There is an additional 12 month follow-up for UK patients for whom the 12 month post-operative time point falls before the end of the planned follow-up period i.e. 90 days following the last participant’s operation; patients will complete quality of life and health resource use questionnaires at this time point but will not need to be seen in clinic at this time as the clinical trial follow-up data will be collected from their medical notes. For patients in the microbiome sub-study (UK patients only), faecal samples will be taken at baseline, intra-op, and at 3-5 days post operatively. Previous interventions: 880 participants will be randomised prior to surgery, on a 1:1 basis, to either surgery with IFA or surgery without IFA using minimisation (incorporating a random element) and stratified by surgeon, gender, ASA grade, T-stage, neo-adjuvant therapy and tumour position. Participants will receive an anterior resection either with or without IFA (intraoperative fluorescence angiography) depending on their randomised allocation: Surgery with no IFA: The anterior resection (high or low) will be performed according to the surgeon’s usual technique, using either a laparoscopic or robotic approach, with white light assessment of bowel perfusion. The specifics of each operation will be at the discretion of the operating surgeon. Surgery with IFA: The anterior resection (high or low) will be performed according to the surgeon’s usual technique, using either a laparoscopic or robotic approach. ICG (Indocyanine Green) will be administered intravenously at two points during the operation for perfusion assessment using near-infrared laparoscopy. A third dose of ICG will be permitted (e.g. extracorporeal assessment, or immediately prior to anastomosis) should the surgeon feel this to be beneficial. The specifics of each operation, including the decision to make a change to the planned anastomosis following IFA assessment, will be at the discretion of the operating surgeon. All patients will be followed up until 90 days post-operation. Patients will be seen in clinic at 30 days and 90 days post operation, and a rectal contrast enema scan will be performed at 4-6 weeks post operation. Patients will complete quality of life and health resource use questionnaires at baseline, 30 and 90 days post operation. For patients in the microbiome sub-study (200 UK patients), faecal samples will be taken at baseline, intra-op and at 3-5 days post operatively. For patients in the perfusion sub-study, two additional scans will be performed pre-operatively (CT angiography and CT perfusion).
Intervention type	Procedure/Surgery
Primary outcome measure	Clinical anastomotic leak rate is defined as per the International Study Group of Rectal Cancer definition, as a confirmed defect of the intestinal wall at the anastomotic site (including suture and staple lines of neorectal reservoirs) leading to a communication between the intra- and extraluminal compartments that has an impact on patient management, as assessed through clinical examination within 90 days post operation
Secondary outcome measures	Current secondary outcome measures as of 19/02/2021: 1. Change in planned anastomosis during surgery, including the decision to undertake a permanent stoma rather than an anastomosis, the site of proximal bowel used for anastomosis, the site of rectal remnant used for anastomosis, and the decision to undertake a diverting stoma 2. Rate of defunctioning stoma (temp or permanent) 3. Operative and post-operative complications (Clavien-Dindo for complication-level classification and Comprehensive Complication Indicator for patient-level classification) within 90 days of operation 4. Length of post-operative hospital stay 5. Low Anterior Resection Syndrome (LARS) score at 30 days and at 90 days post-operation in patients without defunctioning ileostomy 6. Rate of re-interventions within 90 days 7. Quality of life is assessed using the QLQ-C30, QLQ-CR29, and EQ-5D at 30 days and 90 days post-operation 8. Health resource utilisation assessed at 30 days and 90 days post-operation 9. Death within 90 days of operation Mechanistic sub-study: 1. Changes in rectal microbiome and correlation to anastomotic leak Previous secondary outcome measures: 1. Change in planned anastomosis during surgery, including the decision to undertake a permanent stoma rather than an anastomosis, the site of proximal bowel used for anastomosis, the site of rectal remnant used for anastomosis, and the decision to undertake a diverting stoma 2. Rate of defunctioning stoma (temp or permanent) 3. Operative and post-operative complications (Clavien-Dindo for complication-level classification and Comprehensive Complication Indicator for patient-level classification) within 90 days of operation 4. Length of post-operative hospital stay 5. Low Anterior Resection Syndrome (LARS) score at 30 days and at 90 days post-operation in patients without defunctioning ileostomy 6. Rate of re-interventions within 90 days 7. Quality of life is assessed using the QLQ-C30, QLQ-CR29 and EQ-5D at 30 days and 90 days post-operation 8. Health resource utilisation assessed at 30 days and 90 days post-operation 9. Death within 90 days of operation Mechanistic sub-study 1. Presence of vascular variants, presence of atherosclerosis within IMA 2. Presence of stenosis (≤or >50%) in the internal iliac artery, internal pudendal artery, superior rectal, middle rectal or inferior rectal artery 12. Difference in regional blood flow, blood volume or permeability surface area product in patient with or without anastomotic leak, no and prior (chemo)radiation, and intra-operative fluorescence 13. Changes in rectal microbiome and correlation to anastomotic leak
Overall study start date	01/09/2016
Completion date	14/02/2024

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	Planned Sample Size: 880; UK Sample Size: 440
Key inclusion criteria	1. Aged 18 years and over 2. Able to provide written informed consent. 3. Diagnosis of rectal cancer (defined as a lower margin up to 15cm from the anal verge as assessed by endoscopic or radiological assessment) 4. Suitable for curative resection by high or low anterior resection 5. Suitable for elective laparoscopic or robotic surgery 6. ASA less than or equal to 3 7. Able and willing to comply with the terms of the protocol including QoL questionnaires
Key exclusion criteria	Current participant exclusion criteria as of 19/02/2021: 1. Patients not undergoing colo-rectal/anal anastomosis e.g. abdominoperineal excision of rectum (APER), Hartmann’s procedure 2. Patients undergoing synchronous colonic resections 3. Locally advanced rectal cancer requiring extended or multi-visceral excision 4. Recurrent rectal cancer 5. Coexistent colorectal pathology e.g. synchronous cancers, inflammatory bowel disease 6. Previous pelvic radiotherapy for pathology unrelated to diagnosis with rectal cancer e.g. treatment for prostate cancer 7. Hepatic dysfunction, defined as Model for End-Stage Liver Disease (MELD) Score > 10 8. Renal dysfunction, defined as eGFR < 40mmol/l 9. Known allergy to ICG, iodine, iodine dyes, or taking drugs known to interact with ICG e.g. anticonvulsants, bisulphite containing drugs, methadone, nitrofuratoin 10. Pregnant or likely to become pregnant within 3 months of surgery 11. Immunocompromised patients e.g. taking steroids or receiving immunotherapy Previous participant exclusion criteria: 1. Patients not undergoing colo-rectal/anal anastomosis e.g. abdominoperineal excision of rectum (APER), Hartmann’s procedure 2. Patients undergoing synchronous colonic resections 3. Locally advanced rectal cancer requiring extended or multi-visceral excision 4. Recurrent rectal cancer 5. Coexistent colorectal pathology e.g. synchronous cancers, inflammatory bowel disease 6. Previous pelvic radiotherapy for pathology unrelated to diagnosis with rectal cancer e.g. treatment for prostate cancer 7. Hepatic dysfunction, defined as Model for End-Stage Liver Disease (MELD) Score > 10 8. Renal dysfunction, defined as eGFR < 40mmol/l 9. Known allergy to ICG, iodine, iodine dyes, or drugs known to interact with ICG e.g. anticonvulsants, bisulphite containing drugs, methadone, nitrofuratoin 10. Use of oral antibiotics within 8 weeks prior to randomisation 11. Pregnant or likely to become pregnant within 3 months of surgery
Date of first enrolment	01/07/2017
Date of final enrolment	31/07/2023

Locations

Countries of recruitment

Belgium
England
Germany
Ireland
Italy
Netherlands
Slovenia
United Kingdom

Study participating centre

St James’s University Hospital

Beckett Street
Leeds
LS9 7TF
United Kingdom

Sponsor information

University of Leeds
University/education

Faculty of Medicine and Health Research Office
Leeds
LS2 9NL
England
United Kingdom

Phone	+44 113 34 37587
Email	governance-ethics@leeds.ac.uk
"ROR"	https://ror.org/024mrxd33

Funders

Funder type

Government

National Institute for Health Research
Government organisation / National government

Alternative name(s): National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
Location: United Kingdom

Results and Publications

Intention to publish date	31/03/2025
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Data sharing statement to be made available at a later date
Publication and dissemination plan	Current publication and dissemination plan as of 19/02/2021: Planned publication in a high-impact peer-reviewed journal approximately in 2023. Previous publication and dissemination plan: Planned publication in a high-impact peer-reviewed journal approximately in 2022.
IPD sharing plan	The current data-sharing plans for the current study are unknown and will be made available at a later date.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
HRA research summary			28/06/2023	No	No
Results article	version 1.0	26/02/2025	26/02/2025	Yes	No

Additional files

ISRCTN13334746 IntAct_Lay Summary of Trial Results_V1.0_26Feb2025.pdf

Editorial Notes

26/02/2025: A plain English summary of results was uploaded as an additional file.
27/01/2025: The following changes were made to the trial record:
1. The overall end date was changed from 30/11/2023 to 14/02/2024.
2. The intention to publish date was changed from 31/07/2024 to 31/03/2025.
23/05/2023: The following changes have been made:
1. The overall trial end date has been changed from 31/10/2023 to 30/11/2023.
2. The recruitment end date has been changed from 31/07/2023 to 31/07/2023.
3. The intention to publish date has been changed from 01/06/2024 to 31/07/2024.
18/01/2023: The following changes have been made:
1. The overall trial end date has been changed from 31/01/2023 to 31/10/2023.
2. The recruitment end date has been changed from 31/03/2022 to 31/07/2023.
3. The intention to publish date has been changed from 31/07/2023 to 01/06/2024.
19/02/2021: The following changes have been made:
1. The recruitment end date has been changed from 31/08/2020 to 31/03/2022.
2. The overall trial end date has been changed from 31/05/2021 to 31/01/2023.
3. The intention to publish date has been changed from 31/12/2022 to 31/07/2023.
4. The intervention has been updated.
5. The secondary outcome measures have been updated.
6. The participant exclusion criteria have been updated.
7. The countries of recruitment "Germany", "Slovenia", "Belgium", "Netherlands", "Italy", and "Ireland" have been added.
8. The publication and dissemination plan has been updated.
9. The sponsor type has been changed from "Hospital/treatment centre" to "University/education".
26/03/2019: The condition has been changed from "Specialty: Surgery, Primary sub-specialty: Colorectal Surgery; UKCRC code/ Disease: Cancer/ Malignant neoplasms of digestive organs" to "Colorectal cancer" following a request from the NIHR.
13/06/2018: Cancer Research UK lay summary link added to plain English summary field
14/05/2018: Internal review.
16/01/2018: Internal review.
16/10/2017: Internal review.