Contact information
Type
Public
Primary contact
Ms Julie Croft
ORCID ID
http://orcid.org/0000-0001-7586-3394
Contact details
Clinical Trials Research Unit
Leeds Institute of Clinical Trials Research
University of Leeds
Leeds
LS2 9JT
United Kingdom
+44 113 343 8394
j.croft@leeds.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
34216
Study information
Scientific title
IntAct: Intraoperative Fluorescence Angiography to Prevent Anastomotic Leak in Rectal Cancer Surgery
Acronym
IntAct
Study hypothesis
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
North West - Preston Research Ethics Committee, 20/04/2017, ref: 17/NW/0193
Study design
Randomised; Interventional; Design type: Treatment, Prevention, Imaging, Surgery
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Specialty: Surgery, Primary sub-specialty: Colorectal Surgery; UKCRC code/ Disease: Cancer/ Malignant neoplasms of digestive organs
Intervention
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
Phase
Drug names
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
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 trial start date
01/09/2016
Overall trial end date
31/05/2021
Reason abandoned (if study stopped)
Eligibility
Participant 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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 880; UK Sample Size: 440
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
Recruitment start date
01/07/2017
Recruitment end date
31/08/2020
Locations
Countries of recruitment
United Kingdom
Trial participating centre
St James’s University Hospital
Beckett Street
Leeds
LS9 7TF
United Kingdom
Sponsor information
Organisation
University of Leeds
Sponsor details
Faculty of Medicine and Health Research Office
Leeds
LS2 9NL
United Kingdom
+44 113 34 37587
governance-ethics@leeds.ac.uk
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Government
Funder name
National Institute for Health Research
Alternative name(s)
NIHR
Funding Body Type
government organisation
Funding Body Subtype
Federal/National Government
Location
United Kingdom
Results and Publications
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.
Intention to publish date
31/12/2022
Participant level data
To be made available at a later date
Basic results (scientific)
Publication list