IntAct- IFA to prevent anastomotic leak in rectal cancer surgery

Plain English Summary

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

Study website

Type

Public

Contact name

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

EudraCT/CTIS number

IRAS number

ClinicalTrials.gov number

Secondary identifying numbers

34216

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(s)

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

Study setting(s)

Hospital

Study type

Treatment

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

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

Overall study end date

30/11/2023

Reason abandoned (if study stopped)

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(s)

Patient

Age group

Adult

Lower age limit

18 Years

Sex

Both

Target number of participants

Planned Sample Size: 880; UK Sample Size: 440

Participant 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

Recruitment start date

01/07/2017

Recruitment end date

31/07/2023

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

Organisation

University of Leeds

Sponsor details

Faculty of Medicine and Health Research Office
Leeds
LS2 9NL
England
United Kingdom
+44 113 34 37587
governance-ethics@leeds.ac.uk

Sponsor type

University/education

Website

ROR

https://ror.org/024mrxd33

Funder type

Government

Funder name

National Institute for Health Research

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

Funding Body Type

government organisation

Funding Body Subtype

National government

Location

United Kingdom

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.

Intention to publish date

31/07/2024

Individual participant data (IPD) Intention to share

No

IPD sharing plan

The current data-sharing plans for the current study are unknown and will be made available at a later date.

IPD sharing plan summary

Data sharing statement to be made available at a later date

Study outputs