Intraoperative fluorescence angiography with indocyanine green to prevent anastomotic leak in rectal cancer surgery (IntAct): an unblinded randomised controlled trial
David Jayne, Julie Croft, Neil Corrigan, Philip Quirke, Ronan A. Cahill, Gemma Ainsworth, David Meads, Andrew Kirby, Damian Tolan, Kathryn Gordon, Roel Hompes, Antonino Spinelli, Caterina Foppa, Albert Wolthuis, André D’Hoore, Andrea Vignali, Henry S. Tilney, Catherine Moriarty, Armando Vargas‐Palacios, Caroline Young, Rachel Kelly, Deborah Stocken, Kamal Aryal, Adeel Bajwa, Richard Baker, Kat Baker, Willem Bemelman, Gabriele Bislenghi, Niillas Blind, Petrus Bostrom, Stephen Boyce, Simon Buczaki, Ronan Cahill, Manish Chand, Praminthra Chitsabesan, Carla Coimbra Marques, Julie Cornish, Edward Courtney, Peter Coyne, Chris Cunningham, Stephen Dalton, Emmanuel Decker, Andre D'Hoore, Gabriele Di Benedetto, Ugo Elmore, Charles Evans, Caterina Foppa, Jannice Forssell, Anders Gerdin, John Griffith, Ben Griffiths, Jan Grosek, Mark Gudgeon, Richard Guy, Julian Hance, Dean Harris, Roel Hompes, James Horwood, Tasadooq Hussain, David James, David Jayne, Oliver Jones, Iain Jourdan, Robert Juvan, Martin E. Kreis, Johannes Lauscher, Kai Leong, Christopher Liao, Michael Lim, Ian Lindsey, Sushil Maslekar, Danilo Miskovic, Ahmed Nizar, Gregor Norcic, Marius Paraoan, Ioannis Peristerakis, Simon Phillips, Aaron Quyn, James Read, Tim Rockall, Riccardo Rosati, Martin Rutegard, Peter Sagar, Rick Saunders, Andrea Scala, Chelliah Selvasekar, Mohamed Shaban, Ralph Smith, Sebastian Smolarek, Antonino Spinelli, Nicholas Symons, Pieter Tanis, Mohamed A Thaha, Jim Tiernan, Henry Tilney, Ales Tomazic, Jared Torkington, Jurriaan Tuynman, Vamsi Velchuru, Andrea Vignali
Abstract
BACKGROUND: Data are mixed on whether indocyanine green (ICG) fluorescence angiography can reduce the high rate of anastomotic leaks in patients undergoing surgery for rectal cancer. Therefore, we aimed to investigate the safety and efficacy of ICG fluorescence angiography in reducing the rate of clinical anastomotic leaks in these patients. METHODS: IntAct was an unblinded randomised controlled trial conducted at 28 specialist rectal cancer centres across eight European countries. Adults (≥18 years) with rectal cancer (lower margin of cancer ≤15 cm from the anal verge) medically fit for elective, curative, laparoscopic or robotic high or low anterior resection were eligible. Patients not undergoing colorectal or anal anastomosis and those with synchronous colonic tumours or recurrent or locally advanced rectal cancer requiring extended or multi-visceral excision were excluded. Eligible participants were randomly assigned (1:1) by use of minimisation with a random element to undergo surgery with or without ICG (standard care). Resections and anastomoses were done per surgeon preference. In the ICG group, surgeons first marked proximal transection levels via standard white-light laparoscopy and then administered an intravenous bolus of 0·1 mg/kg of ICG for perfusion assessment. A second 0·1 mg/kg ICG assessment was done following anastomosis. In the standard care group, only a white-light assessment of bowel perfusion was performed. The primary endpoint was the rate of clinical anastomotic leak (grades B or C, per the International Study Group of Rectal Cancer) within 90 postoperative days. Analyses were done in the intention-to-treat population for complete cases. This trial is registered with the ISRCTN registry (ISRCTN13334746) and is now complete. FINDINGS: Between Oct 20, 2017, and Aug 15, 2023, 2534 patients were assessed for eligibility and 766 participants were randomly assigned (383 to the ICG group and 383 to the standard care group). 501 (65%) of 766 participants were male, 726 (95%) were of White ethnicity, and the median age was 64·0 years (IQR 56·0-72·0). 343 patients in the ICG group and 355 in the standard care group were included in the intention-to-treat analysis. The rates of anastomotic leak were 11 (3%) of 343 in the ICG group and 20 (6%) in the standard care group for grade A, 11 (3%) and 31 (9%) for grade B, and 25 (7%) and 23 (6%) for grade C. Within 90 days, a clinical anastomotic leak occurred in 90 (13%) of 698 participants: 36 (10%) of 343 in the ICG group and 54 (15%) of 355 in the standard care group (adjusted odds ratio 0·667 [95% CI 0·419-1·060]; p=0·087). There were no serious adverse events related to ICG. INTERPRETATION: Although IntAct did not show a significant benefit for ICG fluorescence angiography, a signal towards a reduction in clinical anastomotic leak rate was observed. The benefit of ICG could be in preventing grade A or B leaks, given similar rates of grade C leaks between groups. Future research is needed to standardise ICG fluorescence assessment and understand its relevance to anastomotic leak. FUNDING: National Institute for Health and Care Research Efficacy and Mechanism Evaluation Programme.