FALCON: a Multicenter Randomized Controlled Trial

NCT02558556 | Unknown DMC

• 1 other identifier: NL47718.068.14
• Study Type: interventional
• Target: 308
• Locations: 1 country
• Sites: 1

Brief Summary

Rationale: Several clinical feasibility studies have shown the potential benefit of near-infrared fluorescence (NIRF) imaging using indocyanine green (ICG) for enhanced and earlier biliary anatomy visualization during laparoscopic cholecystectomy with the aim to reduce the number of vascular and biliary injuries. Although the incidence of injuries is low (0.7%), the impact on patients in terms of morbidity, quality of life and costs are dramatic. The Critical View of Safety (CVS) technique is regarded as the safety valve in conventional laparoscopic cholecystectomy (CLC). It is hypothesized that standard application of near-infrared fluorescence imaging during laparoscopic cholecystectomy can be useful to obtain establishment of CVS (at least 5 minutes) earlier and with more certainty regarding visualization when compared to conventional laparoscopic imaging alone. Study design: A multicenter randomized controlled trial with two study arms. Patients scheduled for an elective laparoscopic cholecystectomy will be recruited and randomized at the outpatient clinic (n = 308 total). One group will undergo near-infrared fluorescence cholangiography assisted laparoscopic cholecystectomy (NIRF-LC) and the other group will undergo conventional laparoscopic cholecystectomy (CLC). Compared with standard care, patients in the NIRF-LC group have to receive one preoperative intravenous injection of ICG. This is the only additional minimally invasive action for the patient. Initially, patients participating in this study will not benefit from the application of NIRFC during the surgical procedure. The administration of ICG and the modified laparoscope itself are not related with any kind of additional risk for the patient. Despite the encouraging results from several (pre)clinical feasibility studies, wide clinical acceptance of the routine use of ICG fluorescence laparoscopy is still lacking due to the absence of reliable and validated clinical data. A randomized clinical study is desirable to assess the potential added value of the NIRF imaging technique during laparoscopic cholecystectomy. Strong evidence in favor of routine implementation of this new imaging technique during laparoscopic cholecystectomy, will probably lead to worldwide routine application of the NIRF technique. Therewith long term sustainability of this research project is guaranteed.

Conditions

Cholecystolithiasis; Cholecystitis

Keywords

Laparoscopic cholecystectomy (LC); Indocyanine green (ICG); Near-Infrared Fluorescence Imaging (NIRF); Critical View of Safety (CVS)

Outcome Measures

Primary Outcomes (1)

• time to identification of CVS

  change in time to identification of CVS

  at time of surgery

Secondary Outcomes (10)

• time until identification of the transition of the cystic duct in the gallbladder during dissection of CVS

  at time of surgery

• visualization of CVS and visualization of the transition of the cystic duct and cystic artery in the gallbladder

  at time of surgery

• total surgical time

  at time of surgery

• intraoperative bile leakage from the gallbladder or cystic duct

  at time of surgery

• bile duct injury

  up to 90 days

Study Arms (2)

NIRF-LC

EXPERIMENTAL

This group of patients will undergo near-infrared fluorescence cholangiography assisted laparoscopic cholecystectomy by use of a Laparoscopic Fluorescence Imaging System (Karl Storz), in combination with one intravenous injection of contrast agent ICG. The ICG is given directly after induction of anesthesia in a dose of 1 ml of 2,5 mg/ml solution. Intraoperatively every 2-5 minutes (more often if desired by surgeon) camera is switched to ICG mode for fluorescence cholangiography, until CVS is established. Registration of time until establishment of CVS, visualization of the individual structures as described as secondary endpoints, and total operation time will be done. The complete procedure will be recorded on video.

Device: Laparoscopic Fluorescence Imaging System (Karl Storz); Other: Indocyanine Green

CLC

NO INTERVENTION

This group will undergo conventional laparoscopic cholecystectomy as in standard practice with no other intervention. Registration of time until establishment of CVS, visualization of the individual structures as described as secondary endpoints, and total operation time will be done. The complete procedure will be recorded on video. Postoperatively, as in the NIRF-LC arm, the videos will be analysed to determine whether CVS is actually established, is the transition of the cystic duct into the gallbladder visualized? Is transition of the cystic artery into the gallbladder visualized? Furthermore, cost-minimalisation will be calculated.

Interventions

Laparoscopic Fluorescence Imaging System (Karl Storz) DEVICE

The Laparoscopic Fluorescence Imaging System (incl. laparoscope, light source, light cable) will supply the needs for near-infrared fluorescence imaging with ICG. The hypothesis is that this device will help in visualizing the anatomical structures such as the common bile duct, which are hard to visualize in white light due to the surrounding tissues.

NIRF-LC

Indocyanine Green OTHER

Indocyanine Green will be injected intravenously as a contrast agent for the use of the Laparoscopic Fluorescence Imaging System.

Also known as: ICG

NIRF-LC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Scheduled for elective laparoscopic cholecystectomy
• Normal liver and renal function
• No hypersensitivity for iodine or ICG
• Able to understand nature of the study procedures
• Willing to participate and with written informed consent
• Physical Status Classification: ASA I / ASA II

You may not qualify if:

• Age \< 18 years
• Liver or renal insufficiency
• Known iodine or ICG hypersensitivity
• Pregnancy or breastfeeding
• Not able to understand nature of the study procedure
• Physical Status Classification: ASA III and above
• iv Heparin injection in the last 24 h; (LMWH not contraindicated)

Sponsors & Collaborators

• Maastricht University Medical Center: lead

Study Sites (1)

Maastricht University Medical Center

Maastricht, Limburg, 6229, Netherlands

RECRUITING

Related Publications (21)

• Flum DR, Dellinger EP, Cheadle A, Chan L, Koepsell T. Intraoperative cholangiography and risk of common bile duct injury during cholecystectomy. JAMA. 2003 Apr 2;289(13):1639-44. doi: 10.1001/jama.289.13.1639.

  PMID: 12672731 BACKGROUND

• Fletcher DR, Hobbs MS, Tan P, Valinsky LJ, Hockey RL, Pikora TJ, Knuiman MW, Sheiner HJ, Edis A. Complications of cholecystectomy: risks of the laparoscopic approach and protective effects of operative cholangiography: a population-based study. Ann Surg. 1999 Apr;229(4):449-57. doi: 10.1097/00000658-199904000-00001.

  PMID: 10203075 BACKGROUND

• Nuzzo G, Giuliante F, Giovannini I, Ardito F, D'Acapito F, Vellone M, Murazio M, Capelli G. Bile duct injury during laparoscopic cholecystectomy: results of an Italian national survey on 56 591 cholecystectomies. Arch Surg. 2005 Oct;140(10):986-92. doi: 10.1001/archsurg.140.10.986.

  PMID: 16230550 BACKGROUND

• Waage A, Nilsson M. Iatrogenic bile duct injury: a population-based study of 152 776 cholecystectomies in the Swedish Inpatient Registry. Arch Surg. 2006 Dec;141(12):1207-13. doi: 10.1001/archsurg.141.12.1207.

  PMID: 17178963 BACKGROUND

• Way LW, Stewart L, Gantert W, Liu K, Lee CM, Whang K, Hunter JG. Causes and prevention of laparoscopic bile duct injuries: analysis of 252 cases from a human factors and cognitive psychology perspective. Ann Surg. 2003 Apr;237(4):460-9. doi: 10.1097/01.SLA.0000060680.92690.E9.

  PMID: 12677139 BACKGROUND

• Strasberg SM, Hertl M, Soper NJ. An analysis of the problem of biliary injury during laparoscopic cholecystectomy. J Am Coll Surg. 1995 Jan;180(1):101-25. No abstract available.

  PMID: 8000648 BACKGROUND

• Buddingh KT, Nieuwenhuijs VB, van Buuren L, Hulscher JB, de Jong JS, van Dam GM. Intraoperative assessment of biliary anatomy for prevention of bile duct injury: a review of current and future patient safety interventions. Surg Endosc. 2011 Aug;25(8):2449-61. doi: 10.1007/s00464-011-1639-8. Epub 2011 Apr 13.

  PMID: 21487883 BACKGROUND

• Ford JA, Soop M, Du J, Loveday BP, Rodgers M. Systematic review of intraoperative cholangiography in cholecystectomy. Br J Surg. 2012 Feb;99(2):160-7. doi: 10.1002/bjs.7809. Epub 2011 Dec 19.

  PMID: 22183717 BACKGROUND

• Agarwal BB. Patient safety in laparoscopic cholecystectomy. Arch Surg. 2009 Oct;144(10):979; author reply 979. doi: 10.1001/archsurg.2009.180. No abstract available.

  PMID: 19841374 BACKGROUND

• Figueiredo JL, Siegel C, Nahrendorf M, Weissleder R. Intraoperative near-infrared fluorescent cholangiography (NIRFC) in mouse models of bile duct injury. World J Surg. 2010 Feb;34(2):336-43. doi: 10.1007/s00268-009-0332-8.

  PMID: 20033407 BACKGROUND

• Figueiredo JL, Nahrendorf M, Vinegoni C, Weissleder R. Intraoperative near-infrared fluorescent cholangiography (NIRFC) in mouse models of bile duct injury: reply. World J Surg. 2011 Mar;35(3):694-5. doi: 10.1007/s00268-010-0728-5. No abstract available.

  PMID: 20645091 BACKGROUND

• Tagaya N, Shimoda M, Kato M, Nakagawa A, Abe A, Iwasaki Y, Oishi H, Shirotani N, Kubota K. Intraoperative exploration of biliary anatomy using fluorescence imaging of indocyanine green in experimental and clinical cholecystectomies. J Hepatobiliary Pancreat Sci. 2010 Sep;17(5):595-600. doi: 10.1007/s00534-009-0195-2. Epub 2009 Oct 6.

  PMID: 19806299 BACKGROUND

• Matsui A, Tanaka E, Choi HS, Winer JH, Kianzad V, Gioux S, Laurence RG, Frangioni JV. Real-time intra-operative near-infrared fluorescence identification of the extrahepatic bile ducts using clinically available contrast agents. Surgery. 2010 Jul;148(1):87-95. doi: 10.1016/j.surg.2009.12.004. Epub 2010 Feb 1.

  PMID: 20117813 BACKGROUND

• Ishizawa T, Bandai Y, Ijichi M, Kaneko J, Hasegawa K, Kokudo N. Fluorescent cholangiography illuminating the biliary tree during laparoscopic cholecystectomy. Br J Surg. 2010 Sep;97(9):1369-77. doi: 10.1002/bjs.7125.

  PMID: 20623766 BACKGROUND

• Ishizawa T, Kaneko J, Inoue Y, Takemura N, Seyama Y, Aoki T, Beck Y, Sugawara Y, Hasegawa K, Harada N, Ijichi M, Kusaka K, Shibasaki M, Bandai Y, Kokudo N. Application of fluorescent cholangiography to single-incision laparoscopic cholecystectomy. Surg Endosc. 2011 Aug;25(8):2631-6. doi: 10.1007/s00464-011-1616-2. Epub 2011 Mar 18.

  PMID: 21424202 BACKGROUND

• Aoki T, Murakami M, Yasuda D, Shimizu Y, Kusano T, Matsuda K, Niiya T, Kato H, Murai N, Otsuka K, Kusano M, Kato T. Intraoperative fluorescent imaging using indocyanine green for liver mapping and cholangiography. J Hepatobiliary Pancreat Sci. 2010 Sep;17(5):590-4. doi: 10.1007/s00534-009-0197-0. Epub 2009 Oct 21.

  PMID: 19844652 BACKGROUND

• Schols RM, Bouvy ND, Masclee AA, van Dam RM, Dejong CH, Stassen LP. Fluorescence cholangiography during laparoscopic cholecystectomy: a feasibility study on early biliary tract delineation. Surg Endosc. 2013 May;27(5):1530-6. doi: 10.1007/s00464-012-2635-3. Epub 2012 Oct 18.

  PMID: 23076461 BACKGROUND

• Mitsuhashi N, Kimura F, Shimizu H, Imamaki M, Yoshidome H, Ohtsuka M, Kato A, Yoshitomi H, Nozawa S, Furukawa K, Takeuchi D, Takayashiki T, Suda K, Igarashi T, Miyazaki M. Usefulness of intraoperative fluorescence imaging to evaluate local anatomy in hepatobiliary surgery. J Hepatobiliary Pancreat Surg. 2008;15(5):508-14. doi: 10.1007/s00534-007-1307-5. Epub 2008 Oct 4.

  PMID: 18836805 BACKGROUND

• Ashitate Y, Stockdale A, Choi HS, Laurence RG, Frangioni JV. Real-time simultaneous near-infrared fluorescence imaging of bile duct and arterial anatomy. J Surg Res. 2012 Jul;176(1):7-13. doi: 10.1016/j.jss.2011.06.027. Epub 2011 Jul 14.

  PMID: 21816414 BACKGROUND

• Schols RM, Bouvy ND, van Dam RM, Masclee AA, Dejong CH, Stassen LP. Combined vascular and biliary fluorescence imaging in laparoscopic cholecystectomy. Surg Endosc. 2013 Dec;27(12):4511-7. doi: 10.1007/s00464-013-3100-7. Epub 2013 Jul 23.

  PMID: 23877766 BACKGROUND

• van den Bos J, Schols RM, Luyer MD, van Dam RM, Vahrmeijer AL, Meijerink WJ, Gobardhan PD, van Dam GM, Bouvy ND, Stassen LP. Near-infrared fluorescence cholangiography assisted laparoscopic cholecystectomy versus conventional laparoscopic cholecystectomy (FALCON trial): study protocol for a multicentre randomised controlled trial. BMJ Open. 2016 Aug 26;6(8):e011668. doi: 10.1136/bmjopen-2016-011668.

  PMID: 27566635 DERIVED

MeSH Terms

Conditions

Cholecystolithiasis; Cholecystitis

Interventions

Indocyanine Green

Condition Hierarchy (Ancestors)

Cholelithiasis; Biliary Tract Diseases; Digestive System Diseases; Gallbladder Diseases

Intervention Hierarchy (Ancestors)

Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Laurents PS Stassen, MD, PhD

  Maastricht UMC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jacqueline van den Bos, MD

CONTACT

0031613206302; jacqueline.vanden.bos@mumc.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2015
• First Posted: September 24, 2015
• Study Start: January 1, 2016
• Primary Completion: December 1, 2019
• Study Completion: July 1, 2020
• Last Updated: March 7, 2019

Record last verified: 2019-03

Locations

NL (1)